scholarly journals Changes in the expression of interleukin-10 in myocardial infarction and its relationship with macrophage activation and cell apoptosis

2019 ◽  
Author(s):  
Wenqi Yang ◽  
Shuming Li ◽  
Yang Zhao ◽  
Ying Sun ◽  
Yuling Huang ◽  
...  

ABSTRACTCurrently, the role of IL-10 as an anti-inflammatory factor in the occurrence and development of heart disease is still unclear. This study aimed to observe the dynamic changes in the expression of IL-10 in serum and myocardial tissues, as well as to investigate the relationship of IL-10 expression with macrophage activation and cardiomyocyte apoptosis during the occurrence of myocardial infarction. Mice models with myocardial infarction were prepared by ligating anterior descending branch of the coronary artery. The animals were classified into sham operation group (the control group), as well as groups of myocardial infarction based on days 1, 7, 14 and 28. On days 7 and 14, the cells with positive IL-10 expression were largely distributed in the infarct areas, while cells with positive IL-10 expression were decreased on day 28. Serum IL-10 was significantly positively correlated with IL-10 protein expression in myocardial tissues. Moreover, Bcl-2 and Bax protein expression in myocardial tissues, as well as the ratio of Bcl-2/Bax proteins were gradually elevated with prolonged time of infarction. There were positive correlations between IL-10 and Arginase expressions, and between the expressions of Bcl-2 and Bax proteins. After the occurrence of myocardial infarction, the expression of IL-10 was firstly increased and then decreased in serum and myocardial tissues, and this might affect macrophage activation, phenotypic transformation and the occurrence of cardiomyocyte apoptosis.

2011 ◽  
Vol 89 (2) ◽  
pp. 109-115 ◽  
Author(s):  
Song Zhang ◽  
Ben He ◽  
Steven Goldstein ◽  
Junbo Ge ◽  
Zuyue Wang ◽  
...  

The aims of this study were to explore the changes in expression of myocardial adiponectin (APN), changes in serum APN, and the significance of bisoprolol intervention in acute myocardial infarction (AMI) rats. An AMI rat model was established for the purposes of this study and was used for analysis of serum APN as determined by ELISA. Changes in expression of myocardial APN mRNA and APN protein in AMI rats were determined via reverse transcriptase (RT)–PCR and immunohistochemistry. Serum APN concentration and APN protein expression of the myocardium decreased significantly in the AMI groups compared with the sham operation group, with the lowest serum APN and APN protein expression on day 7 after AMI. On days 7 and 10 after AMI, the expression of myocardial APN mRNA in the AMI groups decreased significantly compared with the sham operation group. However, the APN mRNA increased on day 10 compared with that on day 7. Notably, there was an increase in levels of serum APN and myocardial APN expression after bisoprolol intervention. The expression of myocardial APN and serum APN decreased in AMI rats. APN may be an important protective factor against AMI. Bisoprolol can also protect against AMI because it increases APN expression.


2019 ◽  
Vol 22 (2) ◽  
pp. E107-E111
Author(s):  
Hongwei Shi ◽  
Zhenming Jiang ◽  
Teng Wang ◽  
Yongting Chen ◽  
Feng Cao

Background: The status of the swelling-activated chloride channel (ICl, swell) during heart failure remains unclear. This study aimed to investigate whether the ICl, swell activity is altered during heart failure and to determine how the ICl, swell influences atrial arrhythmias of the failing heart. Methods: We established a heart failure rabbit model and analyzed the hemodynamic indicators 8 weeks after myocardial infarction, which include left ventricular systolic pressure (LVSP) and left ventricular end-diastolic pressure (LVDEP). Five untreated rabbits and 5 receiving a sham operation served as the control group. Left auricular appendage tissues were obtained and CLCN3 mRNA/CLCN3 protein expression levels were examined by using reverse transcription–polymerase chain reaction and Western blot, respectively. Results: Compared to the control group, the heart failure group showed a significantly decreased LVSP (14.2 ± 0.27 versus 16.9 ± 0.86 kPa, P <.05)and elevated LVDEP (2.49 ± 0.30 versus 0.15 ± 0.03 kPa, P <.05), indicating that myocardial infarction leads to progressive heart failure of rabbits in the heart failure group. CLCN3 mRNA and CLCN3 protein expression were both significantly elevated in the heart failure group compared to the control group (P <.05). Conclusion: In sum, we propose that the dynamic nature of ICl, swell upregulation may contribute to the elevated expression of CLCN3 mRNA and CLCN3 protein, resulting in myocardial cell remodeling induced by heart failure. However, further study is needed to investigate the potential functions of ICl, swell, especially the relation between ICl, swell augmentation and arrhythmia after heart failure.


2020 ◽  
Vol 104 (11-12) ◽  
pp. 968-974
Author(s):  
Sheng-Tao Ling ◽  
Chun-Lei Deng ◽  
Li Huang ◽  
Qi-Sheng Yao ◽  
Cui Liu ◽  
...  

Autophagy is an important pro-survival mechanism and closely related to apoptosis. The aim of this study was to investigate whether hydroxychloroquine (HCQ) blocks autophagy and promotes apoptosis of the prostate after castration. <b><i>Methods:</i></b> Thirty-six male SD rats were randomly divided into 3 groups (<i>n</i> = 12): control group (sham operation), castration group, and HCQ group (castrated and treated with HCQ). On day 7, all mice were executed and prostates were isolated. The morphological changes of prostates were observed by light microscope, and the ultrastructure changes were observed under scanning electron microscope (SEM). The protein expression of Beclin-l, P62, caspase-3, Bcl-2, and Bax was assessed by immunohistochemical analyses. The mRNA expression of microtubule-associated protein light chain 3 (LC3) and autophagy-related gene 5 (Atg5) was detected by RT-PCR. <b><i>Results:</i></b> Prostates of castration group shrank remarkably and prostates of HCQ group shrank more remarkably than castration group. Cytolysosomes were visible in the prostates of the castration group under SEM. Immunohistochemistry showed that the protein of Beclin-1 increased in the castration group compared to the control group, while decreased in the HCQ group compared to the castration group. While P62 protein moderately dyed in the control group and weakly dyed in the castration group, it strongly dyed in the HCQ group. Caspase-3 and Bax protein were weakly dyed in the control group but moderately dyed in the castration group and strongly dyed in the HCQ group. The expressions of apoptosis suppressor Bcl-2 were reduced in the castration group and further reduced in the HCQ group compared to the castration group. RT-PCR revealed that the mRNA of LC3 and Atg5 in the castration group increased compared to the control group, while decreased after treated with HCQ. <b><i>Conclusion:</i></b> Autophagy increased after castrated in prostates, while decreased after treated with HCQ; all these indicated that HCQ blocked autophagy and then promoted prostate apoptosis of castrated mice.


2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Tianshu Yang ◽  
Huiyan Qu ◽  
Xiaolong Song ◽  
Qian Liu ◽  
Xiaoli Yang ◽  
...  

Background. Ventricular remodelling is a common pathological change at all stages of heart disease. Luhong granules are widely used in patients with chronic ventricular remodelling after myocardial infarction and can alleviate chest tightness, shortness of breath, and other symptoms. However, its effect on ventricular remodelling remains to be studied. Purpose. In this study, we investigated the effects of these granules on myocardial fibrosis in a rat model of myocardial infarction in vivo. Methods. Male Wistar rats were randomly divided into four groups: the sham operation group, the acute myocardial infarction (AMI) group, the Luhong granule group, and the vancomycin group, with a sample size (n) of 10 rats in each group. The AMI model was established in all rats by ligation of the left anterior descending (LAD) coronary artery (the sham operation group did not undergo ligation). Luhong granules (0.5 ml·kg−1·d−1), vancomycin (0.075 g·ml−1·d−1), and 0.9% saline (5 ml·kg−1·d−1 for the sham operation and AMI groups) were administered orally for 6 weeks. Echocardiography was used to check cardiac structure and function. Myocardial and small intestinal tissue morphology was observed by haematoxylin and eosin (H&E) staining, and heart samples were stained with Masson’s trichrome to analyse myocardial fibrosis. 16S rDNA sequencing was performed to detect changes in the gut flora. The level of trimethylamine N-oxide (TMAO) in plasma samples was quantified by stable isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS). Results. H&E and Masson’s trichrome staining of cardiac tissues showed that Luhong granules could partially reverse ventricular remodelling and improve intestinal barrier function (P<0.05). Echocardiographic analysis showed that, compared with the AMI group, the left ventricular ejection fraction (LVEF) in the Luhong granule group was increased (P<0.05). Stool sequencing and microbiological analysis showed changes in Bacteroidales, Alistipes, Phascolarctobacterium, etc., which can produce TMAO. We found that Luhong granules can reduce Bacteroidales, Alistipes, and Phascolarctobacterium at the genus level. The levels of TMAO and lipopolysaccharides (LPS) in plasma samples were reduced in the Luhong granule group (P<0.05). Conclusions. Our results indicate that Luhong granules reduce TMAO and LPS levels in circulating blood by improving intestinal flora and intestinal barrier function to delay ventricular remodelling after myocardial infarction.


2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jiangfeng Liu ◽  
Huijun Kang ◽  
Jiangfeng Lu ◽  
Yike Dai ◽  
Fei Wang

Abstract Background Poor osseointegration is the key reason for implant failure after arthroplasty,whether under osteoporotic or normal bone conditions. To date, osseointegration remains a major challenge. Recent studies have shown that deferoxamine (DFO) can accelerate osteogenesis by activating the hypoxia signaling pathway. The purpose of this study was to test the following hypothesis: after knee replacement, intra-articular injection of DFO will promote osteogenesis and osseointegration with a 3D printed titanium prosthesis in the bones of osteoporotic rats. Materials and methods Ninety female Sprague–Dawley rats were used for the experiment. Ten rats were used to confirm the successful establishment of the osteoporosis model: five rats in the sham operation group and five rats in the ovariectomy group. After ovariectomy and knee arthroplasty were performed, the remaining 80 rats were randomly divided into DFO and control groups (n = 40 per group). The two groups were treated by intraarticular injection of DFO and saline respectively. After 2 weeks, polymerase chain reaction (PCR) and immunohistochemistry were used to evaluate the levels of HIF-1a, VEGF, and CD31. HIF-1a and VEGF have been shown to promote angiogenesis and bone regeneration, and CD31 is an important marker of angiogenesis. After 12 weeks, the specimens were examined by micro-computed tomography (micro-CT), biomechanics, and histopathology to evaluate osteogenesis and osseointegration. Results The results of PCR showed that the mRNA levels of VEGF and CD31 in the DFO group were significantly higher than those in the control group. The immunohistochemistry results indicated that positive cell expression of HIF-1a, VEGF, and CD31 in the DFO group was also higher. Compared with the control group, the micro-CT parameters of BMD, BV/TV, TB. N, and TB. Th were significantly higher. The maximal pull-out force and the bone-to-implant contact value were also higher. Conclusions The local administration of DFO, which is used to activate the HIF-1a signaling pathway, can promote osteogenesis and osseointegration with a prosthesis in osteoporotic bone.


2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Demin Liu ◽  
Jing Wang ◽  
Haijuan Hu ◽  
Guoqiang Gu ◽  
Rui Ding ◽  
...  

Background. Hypertension contributes to the progression of cardiac remodeling and renal damage. In turn, renal sympathetic hyperactivation showed elevated sympathetic nervous system activity and led to blood pressure increase in certain patients. The purpose of this study was to observe the effect of renal nerve denervation on blood pressure and target organ changes in two hypertensive rat models. Methods. Hypertensive rats were randomly divided into a renal denervation (RDN) group and sham operation group. Wistar–Kyoto (WKY) rats of the same age were set as the baseline control group. In the secondary hypertension model, SD rats were randomly divided into five groups. Blood pressure and bodyweight were measured every week until they were euthanized. Results. The two rat models underwent RDN at key timepoints. At these timepoints, the hearts and kidneys were collected for norepinephrine and angiotensin II measurements and histological analysis. Conclusion. RDN performed before development of hypertension showed a significant antihypertensive effect on the secondary hypertension model.


2021 ◽  
Vol 12 ◽  
Author(s):  
Lan Ma ◽  
Xiaoce Dai ◽  
Chenxia Wu ◽  
Mingshuang Li ◽  
Hongzhuan Sheng ◽  
...  

We previously demonstrated that the Tanyu Tongzhi Formula (TTF) significantly alleviated the clinical symptoms of patients with coronary heart disease and lowered serum lipid and inflammatory factor levels in patients with coronary heart disease and atherosclerosis model rats. However, the mechanism underlying TTF remains unknown. In this study, we examined the effect of TTF on atherosclerotic plaques in ApoE-/- mice and underlying mechanisms involved in macrophage polarization. Sixty male ApoE-/- mice were randomly divided into four groups. Mice in the control group were fed a regular diet, whereas experimental mice were fed a high-fat diet and received either saline (HFD group) or TTF at concentrations of 0.60 (TTF-L group) or 2.25 g/ml (TTF-H group) by daily oral gavage for 16 weeks. In the TTF-L and TTF-H groups, the levels of serum cholesterol, triglyceride, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α were decreased, lipid content was significantly decreased, and percentage area of collagen/lipid increased in atherosclerotic plaque compared to in the HFD group. Moreover, we found TTF promoted the expression of alternative macrophage markers (Fizz1, Arg1, and Mrc) and suppressed the expression of M1 macrophage markers (TNF-α, IL-1β, and IL-6) by regulating peroxisome proliferator-activated receptor γ (PPARγ) expression and AKT/extracellular signal-regulated kinase (ERK) activation. We further investigated whether alternative macrophage was reduced when PPARγ was inhibited or the AKT/ERK signaling pathway was activated. TTF delayed atherosclerotic plaque progression by promoting alternative macrophage activation through increasing PPARγ expression and inhibiting AKT/ERK phosphorylation, providing a theoretical basis for its clinical application.


2022 ◽  
Vol 32 (1) ◽  
Author(s):  
Chengren Gou ◽  
Tong Liu ◽  
Zongping Chen ◽  
Zidong Zhou ◽  
Tao Song ◽  
...  

Abstract Background The ischiocavernosus muscle (ICM) encompasses a pair of short pinnate muscles attached to the pelvic ring. The ICM begins at the ischial tuberosity and ends at the crus of the penis while covering the surface of the crus. According to the traditional view, the contraction of the ICM plays an auxiliary role in penile erection. However, we have previously shown that the ICM plays an important role in penile erection through an indirect method of diagnosing erectile dysfunction (ED) caused by ICM injury by observing the infertility of paired female rats. Since intracavernosal pressure (ICP) is the current gold standard for diagnosing ED, this study aimed to amputate unilaterally/bilaterally the ICM to establish an ED model by detecting the ICP, recording the infertility of matching female rats, and comparing the two methods. Results Forty sexually mature adult male rats were selected and randomly divided into the following groups: the control group (n = 10), sham operation group (n = 10), unilateral ischiocavernosus muscle (Uni-ICM) amputation group (n = 10), and bilateral ischiocavernosus muscle (Bi-ICM) amputation group (n = 10). Eighty female reproductive rats were randomly assigned to the above groups at a ratio of 2:1. We evaluated the time to conception for the paired female rats and the effects of unilateral/bilateral severing of the ICM on erectile function. The results showed that the baseline and maximum intracavernosal pressure (ICP) in the control group, sham operation group, Uni-ICM amputation group, and Bi-ICM amputation group were 17.44±2.50 mmHg and 93.51±10.78 mmHg, 17.81±2.81 mmHg and 95.07±10.40 mmHg, 16.73±2.11 mmHg and 83.49±12.38 mmHg, and 14.78±2.78 mmHg and 33.57±6.72 mmHg, respectively, immediately postsurgery. The max ICP in the Bi-ICM amputation group was lower than that in the remaining three groups (all P<0.05). The pregnancy rates were 100, 100, 90, and 0% in the control group, sham operation group, Uni-ICM amputation group, and the Bi-ICM amputation group, respectively. The pregnancy rate in the Bi-ICM amputation group was significantly lower than that in the remaining groups (all P<0.05). The time to conception was approximately 7–10 days later in the Uni-ICM amputation group than in the control and sham groups (all P<0.05). Conclusions Male rats undergoing Bi-ICM amputation may develop permanent ED, which affects their fertility. In contrast, rats undergoing Uni-ICM amputation may experience transient ED.


2020 ◽  
Vol 8 (10) ◽  
pp. 643-643
Author(s):  
Wenqi Yang ◽  
Shuming Li ◽  
Yang Zhao ◽  
Ying Sun ◽  
Yuling Huang ◽  
...  

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiangxue Lu ◽  
Shixiang Wang ◽  
Sujuan Feng ◽  
Han Li

Abstract Background Hydrogen sulfide (H2S) has been shown to inhibit the atherosclerosis development and progression. It is produced by cystathionine γ-lyase (CSE) in the cardiovascular system. In our previous study, it has been shown that CSE/H2S system plays a significant role in the changes of uremic accelerated atherosclerosis (UAAS), but the mechanism is not known clearly. Methods In this study, we explored the antagonism of CSE/H2S system in UAAS and identified its possible signaling molecules in ApoE−/− mice with 5/6 nephrectomy and fed with atherogenic diet. Mice were divided into sham operation group (sham group), UAAS group, sodium hydrosulfide group (UAAS+NaHS group) and propargylglycine group (UAAS+PPG group). Serum creatinine, urea nitrogen, lipid levels and lesion size of atherosclerotic plaque in the aortic roots were analyzed. Meanwhile, the expression of CSE, TGF-β and phosphorylation of Smad3 were detected. Results Compared with sham group, the aortic root of ApoE−/− mice in the UAAS group developed early atherosclerosis, the levels of total cholesterol, triglyceride, low-density lipoprotein-cholesterol, serum creatinine and urea nitrogen were also higher than that in the sham group. NaHS administration can inhibit the development of atherosclerosis, but PPG administration can accelerate the atherosclerosis development. Meanwhile, the protein expression levels of CSE and TGF-β and phosphorylation of Smad3 significantly decreased in the UAAS mice. Treatment of UAAS mice with NaHS inhibited TGF-β protein expression and Smad3 phosphorylation decrease, but PPG treatment had the opposite effect. Conclusions The CSE/H2S system is of great importance for treating atherosclerosis in patients with chronic kidney disease, and it may protect the vascular from atherosclerosis through the TGF-β/Smad pathway.


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