scholarly journals Electroacupuncture Pretreatment Attenuates Intestinal Injury after Autogenous Orthotopic Liver Transplantation in Rats via the JAK/STAT Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Lili Jia ◽  
Wenli Yu ◽  
Hongli Yu ◽  
Yiqi Weng
Keyword(s):  
Liver Transplantation ◽  
Orthotopic Liver Transplantation ◽  
Specific Inhibitor ◽  
Underlying Mechanism ◽  
Multiple Organ ◽  
Intestinal Injury ◽  
Stress Index ◽  
Protective Effects ◽  
Organ Protection

Background. Liver transplantation induces self-injury and affects remote organs, such as the lung, kidney, and intestine. Postoperative intestinal dysfunction has been associated with prolonged hospitalization and affects a patient’s health and quality of life. Electroacupuncture (EA) has been proven effective in multiple organ protection. However, the potential mechanism underlying the protective effects of EA on intestinal injury after liver transplantation remains unclear. Methods. After establishing an autogenous orthotopic liver transplantation (AOLT) model, we studied the effects of EA pretreatment on intestinal injury after AOLT. We used the JAK2-specific inhibitor AG490 to explore the underlying mechanism. Histological analysis and apoptosis assays were used to evaluate intestinal injury. Oxidative stress index and inflammatory response were also measured after AOLT. Furthermore, we detected the phosphorylation levels of JAK2, STAT1, and STAT3 by Western blot. Results. We found that pretreatment with EA alleviated intestinal injury after AOLT, as shown by HE staining and TUNEL methods. EA pretreatment inhibited the expressions of p-JAK2, p-STAT1, and p-STAT3 in the intestines after AOLT. Upon treatment with JAK2-specific inhibitor AG490, intestinal injury was balanced. Conclusion. The data indicated EA pretreatment alleviated intestinal injury after AOLT by inhibiting the JAK/STAT signaling pathway. These results provide basic evidence to support the potential therapeutic efficacy of EA.

scholarly journals Dexmedetomidine Attenuates Orthotopic Liver Transplantation-Induced Acute Gut Injury via α2-Adrenergic Receptor-Dependent Suppression of Oxidative Stress

2019 ◽  
Vol 2019 ◽  
pp. 1-11
Author(s):  
Peibiao Lv ◽  
Tufeng Chen ◽  
Peibin Liu ◽  
Lei Zheng ◽  
Jingling Tian ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Transplantation ◽  
Orthotopic Liver Transplantation ◽  
Adrenergic Receptor ◽  
Protective Role ◽  
Intestinal Injury ◽  
Protective Effects ◽  
Barrier Dysfunction

Patients with orthotopic liver transplantation (OLT) frequently develop acute gut injury (AGI), and dexmedetomidine (Dex) has been reported to exert a protective effect against AGI. We investigated whether Dex protects against AGI through antioxidative stress effects by the Nrf2/HO-1 antioxidative signaling pathway. Rats were randomly allocated into a sham group and six orthotopic autologous liver transplantation (OALT) groups receiving different doses of Dex together with/without α2-adrenergic receptor (AR) blockers. Intestinal tissues were collected to visualize the barrier damage and to measure the indexes of oxidative stress. For in vitro studies, rat intestinal recess epithelial cells (IEC-6) underwent hypoxia/reoxygenation (H/R), and the protective role of Dex was evaluated after α2A-AR siRNA silencing. OALT resulted in increased oxidative stress, significant intestinal injury, and barrier dysfunction. Dex attenuated OALT-induced oxidative stress and intestinal injury, which was abolished by the pretreatment with the nonspecific α2A-AR siRNA blocker atipamezole and the specific α2A-AR siRNA blocker BRL-44408, but not by the specific 2B/C-AR siRNA blocker ARC239. Silencing of α2A-AR siRNA also attenuated the protective role of Dex on alleviating oxidative stress in IEC-6 cells subjected to H/R. Dex exerted its protective effects by activating Nrf2/HO-1 antioxidative signaling. Collectively, Dex attenuates OALT-induced AGI via α2A-AR-dependent suppression of oxidative stress, which might be a novel potential therapeutic target for OALT-induced AGI.

Survival, growth and quality of life in children after orthotopic liver transplantation: A 5 year experience

1991 ◽  
Vol 27 (6) ◽  
pp. 380-385 ◽  
Author(s):  
S. E. CHIN ◽  
R. W. SHEPHERD ◽  
G. J. CLEGHORN ◽  
M. K. PATRICK ◽  
G. JAVORSKY ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Liver Transplantation ◽  
Orthotopic Liver Transplantation

scholarly journals Acupuncture Improved Neurological Recovery after Traumatic Brain Injury by Activating BDNF/TrkB Pathway

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Xiaohong Li ◽  
Chong Chen ◽  
Xiping Yang ◽  
Jingjing Wang ◽  
Ming-liang Zhao ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Specific Inhibitor ◽  
Underlying Mechanism ◽  
Neurological Impairment ◽  
Neurological Recovery ◽  
Protective Effects ◽  
Neural Repair ◽  
Intractable Problem ◽  
Induced Amelioration

How to promote neural repair following traumatic brain injury (TBI) has long been an intractable problem. Although acupuncture has been demonstrated to facilitate the neurological recovery, the underlying mechanism is elusive. Brain-derived neurotrophic factor (BDNF) exerts substantial protective effects for neurological disorders. In this study, we found that the level of BDNF and tropomyosin receptor kinase B (TrkB) was elevated spontaneously after TBI and reached up to the peak at 12 h. Nevertheless, this enhancement is quickly declined to the normal at 48 h. After combined stimulation at the acupoints of Baihui, Renzhong, Hegu, and Zusanli, we found that BDNF and TrkB were still significantly elevated at 168 h. We also observed that the downstream molecular p-Akt and p-Erk1/2 were significantly increased, suggesting that acupuncture could persistently activate the BDNF/TrkB pathway. To further verify that acupuncture improved recovery through activating BDNF/TrkB pathway, K252a (specific inhibitor of TrkB) was treated by injection stereotaxically into lateral ventricle. We observed that K252a could significantly prevent the acupuncture-induced amelioration of motor, sensation, cognition, and synaptic plasticity. These data indicated that acupuncture promoted the recovery of neurological impairment after TBI by activating BDNF/TrkB signaling pathway, providing new molecular mechanism for understanding traditional therapy of acupuncture.

scholarly journals Inhibition of gap junction composed of Cx43 prevents against acute kidney injury following liver transplantation

2019 ◽  
Vol 10 (10) ◽  
Author(s):  
Dongdong Yuan ◽  
Xiaoyun Li ◽  
Chenfang Luo ◽  
Xianlong Li ◽  
Nan Cheng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Transplantation ◽  
Acute Kidney Injury ◽  
Kidney Injury ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Organ Protection ◽  
Cx43 Expression

Abstract Postoperative acute kidney injury (AKI) is a severe complication after liver transplantation (LT). Its deterioration and magnification lead to the increase in mortality. Connexin43 (Cx43) mediates direct transmission of intracellular signals between neighboring cells, always considered to be the potent biological basis of organ damage deterioration and magnification. Thus, we explored the effects of Cx43 on AKI following LT and its related possible mechanism. In this study, alternations of Cx43 expression were observed in 82 patients, receiving the first-time orthotopic LT. We built autologous orthotopic liver transplantation (AOLT) models with Sprague–Dawley (SD) rats in vivo, and hypoxia-reoxygenation (H/R) or lipopolysaccharide (LPS) pretreatment models with kidney tubular epithelial cells (NRK-52E) in vitro, both of which were the most important independent risk factors of AKI following LT. Then, different methods were used to alter the function of Cx43 channels to determine its protective effects on AKI. The results indicated that patients with AKI suffering from longer time of tracheal intubation or intensive care unit stay, importantly, had significantly lower survival rate at postoperative 30 days and 3 years. In rat AOLT models, as Cx43 was inhibited with heptanol, postoperative AKI was attenuated significantly. In vitro experiments, downregulation of Cx43 with selective inhibitors, or siRNA protected against post-hypoxic NRK-52E cell injuries caused by H/R and/or LPS, while upregulation of Cx43 exacerbated the above-mentioned cell injuries. Of note, alternation of Cx43 function regulated the content of reactive oxygen species (ROS), which not only mediated oxidative stress and inflammation reactions effectively, but also regulated necroptosis. Therefore, we concluded that Cx43 inhibition protected against AKI following LT through attenuating ROS transmission between the neighboring cells. ROS alternation depressed oxidative stress and inflammation reaction, which ultimately reduced necroptosis. This might offer new insights for targeted intervention for organ protection in LT, or even in other major surgeries.

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