Electroacupuncture stimulation at Yanglingquan acupoint ameliorates hepatic ischemia-reperfusion injury by down-regulating ET-1 to inhibit TAK1-JNK/p38 pathway

2021 ◽  
Author(s):  
Lai Wei ◽  
Yinyin Su ◽  
Siyou Tan ◽  
Yi Zou ◽  
Yixun Tang ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Signaling Pathway ◽  
Caspase 3 ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Expression Patterns ◽  
Hepatic Ischemia ◽  
Tnf Α ◽  
Hepatic Ischemia Reperfusion ◽  
Liver Tissues

The current study set out to investigate the molecular mechanism of electroacupuncture (EA) stimulation at Yanglingquan acupoint (GB34) in hepatic ischemia-reperfusion injury (HIRI) in rats via regulation of the endothelin-1 (ET-1) mediated transforming growth factor-β-activated kinase-1 (TAK1)-c-Jun NH2-terminal kinase (JNK)/p38 signaling pathway. First, EA stimulation was applied to the constructed rat model of HIRI at GB34. Subsequently, the activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and myeloperoxidase (MPO) in liver tissues were measured. Apoptotic changes in liver tissues in rats with HIRI were observed using TUNEL staining. Western blot assay was employed to determine the expression patterns of Bcl-2, Bax, c-caspase-3 and the activation of TAK1-JNK/p38 signaling pathway, and immunohistochemistry was conducted to determine the protein expression patterns of c-caspase-3 and ET-1. In addition, ELISA was performed to determine the levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 in serum. The results demonstrated a significant decline in the activities of AST and ALT and hepatocyte apoptosis in rats with HIRI following EA stimulation. Meanwhile, EA stimulation brought about decreases in the expression levels of Bcl-2, Bax and c-caspase-3, MPO activity, TNF-α, IL-1β and IL-6 in serum, and diminished those of ET-1 in liver tissues, in addition to inhibiting the TAK1-JNK/p38 signaling pathway. Over-expression of ET-1 could counter the inhibitory effects of EA stimulation of HIRI in rats. Together, our findings indicate that EA stimulation at GB34 down-regulates the expression of ET-1, which inhibits the TAK1-JNK/p38 signaling pathway, consequently alleviating HIRI in rats.

scholarly journals Sevoflurane relieves hepatic ischemia–reperfusion injury by inhibiting the expression of Grp78

2018 ◽  
Vol 38 (5) ◽  
Author(s):  
Di Liu ◽  
Xin Jin ◽  
Chunqi Zhang ◽  
You Shang
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Regulatory Protein ◽  
Liver Homogenate ◽  
Hepatic Ischemia ◽  
Damage Degree ◽  
Tnf Α ◽  
Hepatic Ischemia Reperfusion

Purpose: This article aimed to study the role of sevoflurane pre-conditioning in hepatic ischemia–reperfusion and its potential mechanism. Methods: Rat liver ischemia–reperfusion model was constructed. Serum TNF-α, IL-1β, IL-10, and IL-6 concentrations were detected by ELISA. Malondialdehyde (MDA), superoxide dismutase (SOD), and nitric oxide (NO) in liver homogenate were determined. Hematoxylin–Eosin (HE) staining, Tunel, and immunohistochemistry were performed. Ischemia–reperfusion hepatocyte model was established. Cells transfection was conducted. Apoptosis was observed by flow cytometry. Quantitative real-time PCR (qRT-PCR) and Western blotting analysis were used. Results: Compared with I/R group, liver damage degree, liver cell apoptosis, and glucose regulatory protein 78 (Grp78) expression was obviously reduced in rats of SEV group. TNF-α, IL-1β, and IL-6 concentrations were also significantly increased (P<0.01). MDA and NO concentrations were dramatically lower (P<0.01) and SOD concentration was significantly higher (P<0.01). Apoptosis rate, Grp78, PERK, eIF2α, and p-c-JNK/JNK expression was also significantly decreased (P<0.01). Sevoflurane significantly reduced apoptosis and expression of PERK, eIF2α, p-c-JNK/JNK by inhibiting the expression of Grp78 (P<0.01). Conclusion: Sevoflurane relieves hepatic ischemia–reperfusion injury by inhibiting the expression of Grp78.

scholarly journals D-Pinitol Protected Against Endoplasmic Reticulum Stress and Apoptosis in Hepatic Ischemia-Reperfusion Injury Via Modulation of AFT4-CHOP/GRP78 and Caspase-3 Signaling Pathways

2021 ◽  
Author(s):  
Lei Yan ◽  
Heng Luo ◽  
Xingsheng Li ◽  
Yongyong Li
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Reperfusion Injury ◽  
Caspase 3 ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Clinical Problem ◽  
Hepatic Ischemia ◽  
Pre Treatment ◽  
Hepatic Ischemia Reperfusion

Abstract Background: Hepatic ischemia-reperfusion injury (IRI) is a major unavoidable clinical problem often occurs during various liver surgery and transplantation. D-Pinitol, a cyclic polyol, showed its hepatoprotective efficacy in clinical and experimental settings. Aim: To determine the potential and possible mechanism of pinitol against ER stress regulation-mediated hepatic IRI in experimental rats.Materials and methods: Male SD rats were pre-treated with pinitol for 21 days and then subjected to 60 min. of partial hepatic ischemia followed by 24 h. of reperfusion. Various parameters were evaluated, including liver function tests, inflammatory release, endoplasmic reticulum (ER) stress, apoptosis, and structural modifications.Results: Pre-treatment with pinitol (10 and 20 mg/kg) effectively protected IRI-induced hepatic damage reflected by attenuation of elevated AST, ALT, oxidative stress (SOD, GSH, MDA and NO) and pro-inflammatory cytokines (TNF-α and IL’s) release. Interestingly, western blot and ELISA analysis suggested that pinitol significantly down-regulated the expression of ER stress apoptotic markers, namely GRP78, CHOP, AFT-4, AFT-6α, XBP-1, and caspase-3, 9 and 12. Additionally, pinitol pre-treatment improved mitochondrial function and phosphorylation of ERK1/2 and P38. Pinitol markedly protected IRI-induced hepatic apoptosis determined by flow cytometry. The hepatic histological and ultrastructural aberration induced by IRI was effectively protected by pinitol. Conclusion: Findings of the present investigation suggested that pinitol offered protection against ER stress-mediated phosphorylation of ERK1/2 and p38, thereby inhibited AFT4-CHOP/GRP78 signaling response and induction of caspase-3 induced hepatocellular apoptosis during hepatic ischemia-reperfusion insults.

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