scholarly journals Antitumor activity of flavonoids from Alpinia officinarum hance on gastric cancer

2021 ◽  
Vol 19 ◽  
pp. 205873922110511
Author(s):  
Mirensha Yakufu ◽  
Renaguli Hailiwu ◽  
Yuanyuan Cong ◽  
Ayijiang Habaike ◽  
Xiaomei Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Antitumor Activity ◽  
Dose Group ◽  
Low Dose ◽  
Caspase 3 ◽  
Caspase 8 ◽  
High Dose ◽  
Model Group ◽  
Caspase 9 ◽  
Alpinia Officinarum

Introduction: To investigate antitumor activity and mechanism of flavonoids from Alpinia officinarum Hance against gastric cancer. Methods: Transplanted mouse fore-stomach carcinoma (MFC) tumor mice were divided into six groups: control group, model group, low dose (20 mg/kg), middle dose (40 mg/kg), and high dose (80 mg/kg) groups of TFAO and 5-Fu group. Mice were treated with TFAO or 5-Fu for 14 days, except those of control and model group. Tumor inhibitory rate, spleen, and thymus index were calculated. Contents of proliferating cell nuclear antigen, MMP-9, vascular endothelial growth factor, IL-1β, IL-6, and IL-17 in serum were detected. Effect of galangin on BGC-823 cell growth was detected. Cell apoptosis and cell cycle distribution were measured. Enzyme activity of Caspase-3, Caspase-8, and Caspase-9 was detected. Western blot was used to detect STAT3, Bcl-2, Bax, Caspase-3, Caspase-8, Caspase-9, CyclinB1, and CyclinD1 protein expression in BGC-823 cell. Results: Compared with model group, tumor weight of mice decreased significantly ( p < .01) in 5-Fu group, low dose, middle dose, and high dose group of TFAO; thymus index of mice decreased significantly ( p < .05) in 5-Fu group; and spleen index decreased significantly ( p < .05) in low dose and middle dose groups of TFAO. Compared with model group, levels of PCNA, MMP-9, IL-1β, and IL-6 in serum of mice decreased obviously ( p < .01) in all administration groups; levels of VEGF in serum of mice decreased obviously ( p < .01) in low dose and high dose group of TFAO and 5-Fu group; and levels of IL-17 in serum of mice decreased significantly ( p < .01) in low-dose and middle-dose groups of TFAO and 5-Fu group. Galangin could inhibit BGC-823 cell growth; accelerate apoptosis; block cell cycle; increase cell Caspase-3, Caspase-8, and Caspase-9 enzyme activity; upregulate expression of Caspase-3, Caspase-8, Caspase-9, and Bax; and downregulate expression of STAT3, CyclinB1, CyclinD1, and Bcl-2 protein. Conclusion: Flavonoids from A. officinarum showed antitumor activity in gastric cancer. Mechanisms may be associated with inhibition of tumor angiogenesis, tumor cell proliferation, and cancer-associated inflammation.

scholarly journals Research on the Effects of the Extract of Polygala fallax Hemsl on Sex Hormones and ?-EP in Perimenopausal Rat Models

2020 ◽  
Vol 4 (3) ◽  
Author(s):  
Siyuan Yang ◽  
Zhiyong Cao ◽  
Jiabao Chen ◽  
Gang Fang
Keyword(s):  
Menstrual Cycle ◽  
Sex Hormones ◽  
Dose Group ◽  
Low Dose ◽  
Normal Group ◽  
Dose Effect ◽  
High Dose Group ◽  
High Dose ◽  
Model Group ◽  
Rat Models

Objective: To study the effects of the ethnic medicine Polygala fallax Hemsl with Guangxi characteristics on the sex hormones and ?-EP in research objective perimenopausal rat models. Methods: 40 female SPF rats were randomly divided into 4 groups, including the normal, model, high-dose and low-dose groups. Rats of three groups except for the normal one were treated with perimenopausal modelling through the method of subcutaneous injection of compound 4-VCD for 15 consecutive days. Rats of the normal and model group were normally fed without any treatment. Rats of the high-dose and low-dose groups were administered by high- and low-dose intragastric administration of the extract of Polygala fallax Hemsl. According to the menstrual cycle of the vaginal smear of the rat, each menstrual cycle is a course of treatment and 6 consecutive courses of treatment would be given. The indexes of serum sex hormones (E2, FSH, LH) and ?-EP of rats in each group were observed after treatment. Results: After the treatment of 6 cycles, for the levels of ?-EP and E2, the model group was lowest (P<0.05), the normal group was highest (P<0.05); and the high-dose group was higher than the low-dose group; For the levels of FSH and LH, the normal group was lowest (P<0.05), the model group was highest (P<0.05), and the high-dose group was lower than the low-dose group. Conclusion: Guangxi characteristic national medicine Polygala fallax Hemsl can effectively improve the levels of serum sex hormones and ?-EP in perimenopausal rat models and relieve the related symptoms with a certain dose-effect relationship.

scholarly journals Erteng-Sanjie Capsule Enhances Chemosensitivity of 5-Fluorouracil in Tumor-Bearing Nude Mice with Gastric Cancer by Inhibiting Notch1/Hes1 Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Jing Zhou ◽  
Shulan Hao ◽  
Hao Guo ◽  
Han Yu ◽  
Zhi Guo ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Signaling Pathway ◽  
Microvessel Density ◽  
Dose Group ◽  
Caspase 3 ◽  
Tumor Volume ◽  
Control Group ◽  
Tunel Staining ◽  
High Dose ◽  
Therapeutic Effects

Gastric cancer is one of the most common cancers worldwide. This study investigated the chemosensitivity-enhancing effects of Erteng-Sanjie capsule (ETSJC) in combination with 5-fluorouracil (5-FU) on gastric cancer and its possible underlying mechanisms. The study established a subcutaneous xenograft model of human gastric cancer. The animals were divided into five groups: the control group, the 5-FU group, the 5-FU + ETSJC low-dose group, the 5-FU + ETSJC medium-dose group, and the 5-FU + ETSJC high-dose group. The tumor volume and tumor weight were calculated. TUNEL staining was used to evaluate cell apoptosis. Immunohistochemical analysis was used to detect the expression of Ki67+ cells and the CD31+ microvessel density in tumors. Simultaneously, western blot analysis was applied to detect the expression of caspase-3, Bax, Bcl-2, Notch1, and Hes1 proteins. Compared with the control group, tumor volume and weight in the 5-FU and 5-FU + ETSJC groups were inhibited. Moreover, compared with the 5-FU group, tumor volume and weight were significantly inhibited in the 5-FU + ETSJC groups. The numbers of Ki67+ cells, CD31+ microvessel density, and the expression of Bcl-2, Notch1, and Hes1 proteins were markedly decreased in the combination group when compared with the chemotherapy alone group. The numbers of TUNEL+ cells and the expression of Bax and caspase-3 proteins were significantly increased in the 5-FU + ETSJC groups when compared with the 5-FU group. The therapeutic effects were demonstrated to be dose dependent. In conclusion, the findings of the study showed that ETSJC improved the chemosensitivity of 5-FU by blocking Notch1/Hes1 signaling pathway in gastric cancer-bearing mice.

Combination of a Novel Proteasome Inhibitor NPI-0052 and Lenalidomide Trigger in Vivo Synergistic Cytotoxicity in Multiple Myeloma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3662-3662 ◽  
Author(s):  
Dharminder Chauhan ◽  
Ajita V. Singh ◽  
Mohan Brahmandam ◽  
Giada Bianchi ◽  
Klaus Podar ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Multiple Myeloma ◽  
Cell Lines ◽  
Proteasome Inhibitor ◽  
Low Dose ◽  
Caspase 3 ◽  
Caspase 8 ◽  
Caspase 9

Abstract Background: Our previous study demonstrated that a novel proteasome inhibitor NPI-0052 is distinct from bortezomib in its chemical structure, effects on proteasome activities, and mechanisms of action, and importantly, triggers apoptosis in multiple myeloma (MM) cells resistant to conventional and bortezomib therapies. These preclinical data provided the basis for the ongoing phase-I clinical trial of NPI-0052 in relapsed/refractory MM patients. Recently, a Phase-1/2 clinical trial of bortezomib with Lenalidomide and low dose dexamethasone demonstrated safety and remarkable efficacy in newly diagnosed MM patients. Given that the combination of bortezomib with Lenalidomide has proven a successful treatment strategy, coupled with our findings that NPI-0052 is a potent proteasome inhibitor, we determined whether combining NPI-0052 with Lenalidomide triggered synergistic/additive anti-MM activity. Material and Methods: We utilized MM.1S, MM.1R, RPMI-8226, U266, and INA-6 human MM cell lines, as well as purified tumor cells from patients relapsing after prior therapies including Lenalidomide or bortezomib. Informed consent was obtained from all patients in accordance with the Helsinki protocol. Cell viability and apoptosis assays were performed using MTT and Annexin V staining. In vitro angiogenesis was assessed by Matrigel capillary-like tube structure formation assay. Immunoblot analysis was performed using antibodies to caspase-8, caspase-9, caspase-3, PARP, Bcl-2, BIM, p-JNK or tubulin. In vitro and in vivo proteasome activity assays were performed using fluorogenic peptide substrates. All animal studies were approved by the DFCI Institutional Animal Care and Use Committee. CB-17 SCID male mice (n = 30; 5 mice/EA group) were subcutaneously inoculated with 5.0 × 106 MM.1S cells in 100 microliters of serum free RPMI-1640 medium. When tumors were measurable (~150 mm3) three weeks after MM cell injection, mice were treated with oral doses of vehicle alone, NPI-0052 (0.15 mg/kg), Lenalidomide (2.5 mg/kg), Lenalidomide (5.0 mg/kg), NPI-0052 (0.15 mg/kg) plus Lenalidomide (2.5 mg/kg) or NPI-0052 (0.15 mg/kg) plus Lenalidomide (5.0 mg/kg) on a twice weekly schedule for NPI-0052 and four consecutive days weekly for Lenalidomide for four weeks. Statistical significance of differences observed in NPI-0052, Lenalidomide or NPI-0052 plus Lenalidomide-treated mice was determined using a Student t test. Isobologram analysis was performed using “CalcuSyn” software program. A combination index < 1.0 indicates synergism. Results: Combining NPI-0052 and Lenalidomide induces synergistic/additive anti-MM activity in vitro using MM cell lines (P<0.005, n=3, CI < 1) or patient CD138-positive MM cells (5 patients, P< 0.004). NPI- 0052 plus Lenalidomide-induced synergistic apoptosis is associated with: activation of caspase-8, caspase-9, caspase-3, and PARP; induction of c-Jun-NH2-terminal kinase; activation of BH-3 protein BIM; inhibition of migration of MM cells and angiogenesis; suppression of chymotrypsin-like, caspase-like and trypsin-like proteolytic activities in an additive manner; and inhibition of NF-kappa B signaling. Importantly, blockade of BIM using siRNA significantly abrogates NPI-0052 plus Lenalidomide-induced apoptosis (61 ± 7.1% decrease in cell death; P < 0.003, n=2). Furthermore, studies using biochemical inhibitors of caspase-8 versus caspase-9 demonstrate that NPI-0052 plus Lenalidomide-triggered apoptosis is primarily dependent on caspase-8 signaling. In animal tumor model studies, low dose combination NPI-0052 (0.15 mg/kg) and Lenalidomide (2.5 or 5.0 mg/kg) is well tolerated, significantly inhibits tumor growth (P < 0.03), and prolongs survival (4–5 months in mice receiving combined drugs, P = 0.001). Immununohistochemistry analysis of MM tumors excised from NPI-0052 plus Lenalidomide-treated mice showed growth inhibition (Ki-67), apoptosis (TUNEL assay, caspae-3 activation), a decrease in associated angiogenesis (Factor VIII and VEGF receptor), and additive inhibition of proteasome activity. Taken together, our study provides the preclinical rationale for clinical protocols evaluating Lenalidomide together with NPI-0052 to improve patient outcome in MM.

scholarly journals Proteomic Analysis to Explore the Effect of Zishen Jiangtang Pills on Diabetic Osteoporosis Rats

2020 ◽  
Author(s):  
Shufang Chu ◽  
Deliang Liu ◽  
Hengxia Zhao ◽  
Mumin Shao ◽  
Jianping Chen ◽  
...  
Keyword(s):  
Proteomic Analysis ◽  
Dose Group ◽  
Low Dose ◽  
Fasting Blood Glucose ◽  
High Dose ◽  
Group Model ◽  
Model Group ◽  
Active Ingredients ◽  
Ginsenoside Re ◽  
Diabetic Osteoporosis

Abstract Context Zishen Jiangtang Pill (ZJP) is a Chinese herbal compound that could play a positive role in the treatment of Diabetic osteoporosis (DOP) by regulating glucose and bone metabolism. However, the specific mechanisms are still unclear.Background To explore the effect and mechanism of ZJP on DOP rats by proteomic analysis.Materials and methods After the establishment of diabetes model by 0.2% STZ, 40 Wistar rats were equally divided into normal group, model group (diabetic rats), high dose group (3.0 g/kg/d ZJP) and low dose group (1.5 g/kg/d ZJP), and received 3 months of treatment. Histological changes in bone and pancreas tissues were observed by Hematoxylin and eosin staining, electron microscopy, and immunofluorescence. Proteomic and bioinformatics analyses were performed to identify the differentially expressed proteins. The fingerprint and active ingredients of ZJP were identified via HPLC.Results Compared with the model group, ZJP could rescue the weight, fasting blood glucose and fasting insulin of rats in both high and low dose group. ZJP could also improve the micro-structures of pancreatic islet cells, and bone mass, trabecular and marrow cavities in DOP rats. Bioinformatic analysis suggested that ZJP might influence DOP via multiple pathways, mainly including ribosomes, vitamin digestion and absorption, and fat digestion and absorption. The primary active ingredients, including notoginsenoside R1, ginsenoside Rg1, ginsenoside Re, icariin, and ginsenoside Rb1 were detected.Conclusion ZJP could significantly improve the histomorphology and ultrastructure of bone and islets tissues, and might serve as an effective alternative medicine for the treatment of DOP.

Phase II and UGT1A1 Polymorphism Study of Two Different Irinotecan Dosages Combined with Cisplatin as First-Line Therapy for Advanced Gastric Cancer

Chemotherapy ◽  
2016 ◽  
Vol 61 (4) ◽  
pp. 197-203 ◽  
Author(s):  
Wenna Wang ◽  
Jing Huang ◽  
Yunxia Tao ◽  
Xiao Lyu ◽  
Lin Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Dose Group ◽  
Low Dose ◽  
High Dose Group ◽  
High Dose ◽  
First Line ◽  
First Line Therapy ◽  
Significant Difference ◽  
Grade 3

Background: We investigated the efficacy and safety of biweekly irinotecan and cisplatin (IP) as first-line treatment in advanced gastric cancer patients. Methods: Irinotecan 125 mg/m2 on day 1 and cisplatin 60 mg/m2 on day 2 were administrated every 14 days. UGT1A1*28/*6 and toxicities were analyzed. Results: Forty-one eligible patients were enrolled. Fifteen patients, who were defined as the high-dose group, received starting doses of irinotecan 125 mg/m2. Twenty-six patients, who were defined as the low-dose group, received starting doses of irinotecan 80 mg/m2 and cisplatin 50 mg/m2. The response rate was 53.3% in the irinotecan high-dose group and 53.8% in the irinotecan low-dose group. The most common grade 3/4 toxicity was neutropenia (68.3%). No significant difference in grade 3/4 neutropenia was found between patients with the wild-type genotype and those with variant genotypes for UGT1A1*28 or UGT1A1*6. Conclusions: The combination of biweekly irinotecan 80 mg/m2 and cisplatin 50 mg/m2 was active and tolerable. The role of the UGT1A1 genotype in clinical toxicity of an IP regimen requires further investigation.

The Study of Interference with Ruyanneixiao Cream on Hemorheology and Mammary Microcirculation of Mammary Precancer Rats

2012 ◽  
Vol 554-556 ◽  
pp. 1789-1793
Author(s):  
Gui Juan Zhang ◽  
De Hui Li ◽  
Rui Liao ◽  
Bi Zhu Tan ◽  
Yu Bin Liu ◽  
...  
Keyword(s):  
Dose Group ◽  
Low Dose ◽  
Plasma Viscosity ◽  
Control Group ◽  
High Dose ◽  
Model Group ◽  
Blank Control Group ◽  
Whole Blood Viscosity ◽  
Sd Rats ◽  
The Status

Objective: to probe the interference of Ruyanneixiao cream for hemorheology and mammary microcirculation of mammary precancer rats. Methods: 48 virginal female SD rats were randomly allocated into 6 groups, A: Blank control group (8); B: Mammary precancer model group (8); C: Tamoxifen (TAM) group (8); D: High dose group of Ruyanneixiao cream (8); E: Middle dose group of Ruyanneixiao cream (8); F: Low dose group of Ruyanneixiao cream (8). The changes of hemorheology and mammary microcirculation were recorded when the rats were executed after 60d. Result: compared with the Blank control group, the whole blood viscosity and plasma viscosity of mammary precancer model group was higher (P<0.05) and the perfusion of mammary microcirculation was lower (P<0.01). Compared with mammary precancer model group, the hemorheological parameters and perfusion of mammary microcirculation of each dose group of Ruyanneixiao cream were improved (P<0.05). Conclusion: Ruyanneixiao cream can improve the status of hemorheology, increase the perfusion of mammary microcirculation. And it may be one of mechanism to treat and prevent mammary precancer disease.

scholarly journals Effects and Mechanism of Zishen Jiangtang Pill on Diabetic Osteoporosis Rats Based on Proteomic Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Shufang Chu ◽  
Deliang Liu ◽  
Hengxia Zhao ◽  
Mumin Shao ◽  
Xuemei Liu ◽  
...  
Keyword(s):  
Proteomic Analysis ◽  
Dose Group ◽  
Low Dose ◽  
Fasting Blood Glucose ◽  
High Dose ◽  
Group Model ◽  
Model Group ◽  
Active Ingredients ◽  
Ginsenoside Re ◽  
Diabetic Osteoporosis

Context. Zishen Jiangtang Pill (ZJP) is a Chinese herbal compound, which has a positive therapeutic effect on diabetic osteoporosis (DOP) by regulating glucose metabolism and bone metabolism. However, its regulatory role and mechanism are still unclear. Objective. To explore the effect and mechanism of ZJP on DOP rats by proteomic analysis. Materials and Methods. After the establishment of diabetes model by Streptozocin (STZ, 60 mg/kg), 40 Wistar rats were equally divided into normal group, model group (diabetic rats), high-dose group (3.0 g/kg/d ZJP), and low-dose group (1.5 g/kg/d ZJP) and received treatment for 3 months. Histological changes in bone and pancreas tissues were observed by hematoxylin and eosin staining, electron microscopy, and immunofluorescence. Proteomic and bioinformatic analyses were performed to identify the differentially expressed proteins. The fingerprint and active ingredients of ZJP were identified via high-performance liquid chromatography (HPLC). Results. Compared with the model group, ZJP could rescue the weight, fasting blood glucose, and fasting insulin of rats in both high-dose and low-dose group. ZJP could also improve the microstructures of pancreatic islet cells, bone mass, and trabecular and marrow cavities in DOP rats. Bioinformatic analysis suggested that ZJP might influence DOP via multiple pathways, mainly including ribosomes, vitamin digestion and absorption, and fat digestion and absorption. The primary active ingredients, including notoginsenoside R1, ginsenoside Rg1, ginsenoside Re, icariin, and ginsenoside Rb1, were detected. Conclusion. ZJP could significantly improve the histomorphology and ultrastructure of bone and islets tissues and might serve as an effective alternative medicine for the treatment of DOP.

Intensive Initial Oral Anticoagulation and Shorter Heparin Treatment in Deep Vein Thrombosis

1984 ◽  
Vol 52 (03) ◽  
pp. 276-280 ◽  
Author(s):  
Sam Schulman ◽  
Dieter Lockner ◽  
Kurt Bergström ◽  
Margareta Blombäck
Keyword(s):  
Deep Vein Thrombosis ◽  
Oral Anticoagulation ◽  
Dose Group ◽  
Low Dose ◽  
Clinical Signs ◽  
Coagulation Factor ◽  
High Dose ◽  
Vein Thrombosis ◽  
Heparin Treatment ◽  
Deep Vein

SummaryIn order to investigate whether a more intensive initial oral anticoagulation still would be safe and effective, we performed a prospective randomized study in patients with deep vein thrombosis. They received either the conventional regimen of oral anticoagulation (“low-dose”) and heparin or a more intense oral anticoagulation (“high-dose”) with a shorter period of heparin treatment.In the first part of the study 129 patients were randomized. The “low-dose” group reached a stable therapeutic prothrombin complex (PT)-level after 4.3 and the “high-dose” group after 3.3 days. Heparin was discontinued after 6.0 and 5.0 days respectively. There was no difference in significant hemorrhage between the groups, and no clinical signs of progression of the thrombosis.In the second part of the study another 40 patients were randomized, followed with coagulation factor II, VII, IX and X and with repeated venograms. A stable therapeutic PT-level was achieved after 4.4 (“low-dose”) and 3.7 (“high-dose”) days, and heparin was discontinued after 5.4 and 4.4 days respectively. There were no clinical hemorrhages, the activity of the coagulation factors had dropped to the same level in both groups at the time when heparin was discontinued and no thromboembolic complications occurred.Our oral anticoagulation regimen with heparin treatment for an average of 4.4-5 days seems safe and reduces in-patient costs.

scholarly journals Study on the Mechanism of Shugan Xiaozhi Fang on Cells with Non-alcoholic Fatty Liver Disease

2019 ◽  
Vol 17 (1) ◽  
pp. 1328-1338
Author(s):  
Yufeng Xing ◽  
Chuantao Zhang ◽  
Fenfen Zhai ◽  
Tianran Zhou ◽  
Xiang Cui ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver Disease ◽  
Dose Group ◽  
Control Group ◽  
High Dose ◽  
Model Group ◽  
Alcoholic Fatty Liver ◽  
Oil Red O Staining ◽  
Alcoholic Fatty Liver Disease ◽  
Oil Red O

AbstractCells with non-alcoholic fatty liver disease (NAFLD) were studied to determine the mechanism of liver deficiency via the AdipoR2-PPARa pathway. NAFLD cells were randomly divided into a normal control group, blank control group, model group, low dose group, medium dose group, and high dose group. The NAFLD models were established by incubating the cells with linoleic acid (LA) and palmitic acid (PA) (2:1) for 24 h. The test groups were incubated with different doses of Shugan Xiaozhi Fang extract. The pathological changes in cells that accumulated lipids were detected by Oil Red O staining. Malondialdehyde (MDA) and triglyceride (TG) levels were measured. The apoptosis of cells was evaluated by flow cytometry. The levels of AdipoR2, PPARa, CD36, acyl-CoA mRNA, and protein were confirmed by RT- PCR and Western blot. The results of the Oil Red O staining demonstrated that the NAFLD cell model was successfully established. Compared with the model group, the levels of TG and MDA in the groups that received low, medium, and high doses of Shugan Xiaozhi were significantly lower (P<0.01), and a dose effect was evident. In addition, the expression of AdipoR2, PPARa, CD36, acyl-CoA protein, and mRNA in the Shugan Xiaozhi-treated groups was upregulated. Furthermore, the levels of AdipoR2, PPAR, CD36, acyl-CoA protein, and mRNA in all drug treatment groups that were extracted from L-O2 normal human hepatocytes were significantly upregulated (P<0.01). Moreover, the factor pattern of HepG2 human liver carcinoma cells was similar to that of L-O2. The levels of AdipoR, CD36, acyl-CoA, and AdipoR mRNA in the HepG2 low group were increased (P<0.05). AdipoR, PPAR, CD36, and acyl-CoA protein levels and AdipoR mRNA expression were significantly increased in the intermediate dose group and high dose group (P<0.01). Shugan Xiaozhi Fang attenuates hepatic lipid deposition in NAFLD induced by incubating with LA and PA for 24 h, which is associated with the activation of the AdipoR2-PPARα pathway.

scholarly journals Newly Developed Recombinant Antithrombin Protects the Endothelial Glycocalyx in an Endotoxin-Induced Rat Model of Sepsis

2020 ◽  
Vol 22 (1) ◽  
pp. 176
Author(s):  
Toshiaki Iba ◽  
Jerrold H. Levy ◽  
Koichiro Aihara ◽  
Katsuhiko Kadota ◽  
Hiroshi Tanaka ◽  
...  
Keyword(s):  
Dose Group ◽  
Low Dose ◽  
Leukocyte Adhesion ◽  
Endothelial Glycocalyx ◽  
High Dose Group ◽  
Control Group ◽  
High Dose ◽  
Protective Effects ◽  
Circulating Levels

(1) Background: The endothelial glycocalyx is a primary target during the early phase of sepsis. We previously reported a newly developed recombinant non-fucosylated antithrombin has protective effects in vitro. We further evaluated the effects of this recombinant antithrombin on the glycocalyx damage in an animal model of sepsis. (2) Methods: Following endotoxin injection, in Wistar rats, circulating levels of hyaluronan, syndecan-1 and other biomarkers were evaluated in low-dose or high-dose recombinant antithrombin-treated animals and a control group (n = 7 per group). Leukocyte adhesion and blood flow were evaluated with intravital microscopy. The glycocalyx was also examined using side-stream dark-field imaging. (3) Results: The activation of coagulation was inhibited by recombinant antithrombin, leukocyte adhesion was significantly decreased, and flow was better maintained in the high-dose group (both p < 0.05). Circulating levels of syndecan-1 (p < 0.01, high-dose group) and hyaluronan (p < 0.05, low-dose group; p < 0.01, high-dose group) were significantly reduced by recombinant antithrombin treatment. Increases in lactate and decreases in albumin levels were significantly attenuated in the high-dose group (p < 0.05, respectively). The glycocalyx thickness was reduced over time in control animals, but the derangement was attenuated and microvascular perfusion was better maintained in the high-dose group recombinant antithrombin group (p < 0.05). (4) Conclusions: Recombinant antithrombin maintained vascular integrity and the microcirculation by preserving the glycocalyx in this sepsis model, effects that were more prominent with high-dose therapy.

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