硫化氢抑制自噬减轻肝硬化大鼠肝脏缺血再灌注损伤

发布时间：2018-05-08 20:10

本文选题：肝 + 再灌注损伤　；参考：《中国普通外科杂志》2016年01期

【摘要】：目的:探讨硫化氢(H_2S)预处理对肝硬化大鼠肝脏缺血再灌注损伤(HIRI)的影响及机制。方法:将32只采用胆总管结扎法制作的肝硬化模型大鼠随机均分为4组,分别行假手术(假手术组)、30 min肝门阻断及4 h再灌注诱导HIRI模型(HIRI组)、硫氢化钠(Na HS,外源性H_2S供体)预处理+HIRI模型诱导(Na HS组)、Na HS+雷帕霉素(RPM,m TOR抑制剂)预处理+HIRI模型诱导(RPM组),随后检测血清谷草转氨酶(AST)、谷丙转氨酶(ALT)浓度,分别用光镜与电镜观察肝组织病理学变化与自噬水平,Western blot检测肝组织LC3-II(自噬特异性标记)以及m TOR、磷酸化m TOR(p-m TOR)蛋白表达。结果:除假手术组外,其余各组肝组织在肝硬化表现的基础上均出现明显的炎症反应、细胞肿胀与局灶性坏死等损伤改变,但Na HS组的损伤程度明显轻于HIRI组与RPM组。与假手术组比较,其他各组血清AST、ALT水平均明显升高、肝细胞内自噬体数量明显增多、肝组织LC3-II蛋白表达明显升高,而p-m TOR蛋白表达(p-m TOR/m TOR比值)明显降低(均P0.05),但Na HS组转氨酶升高幅度、细胞内噬体数量、肝组织LC3-II蛋白升高及p-m TOR蛋白降低程度均明显低于HIRI组(均P0.05),而RPM组与HIRI组间各项指标差异均无统计学意义(均P0.05)。结论:H_2S预处理能减轻肝硬化大鼠HIRI,其机制可能与通过活化m TOR途径抑制自噬有关。
[Abstract]:Aim: to investigate the effect and mechanism of H _ 2S preconditioning on hepatic ischemia-reperfusion injury in cirrhotic rats. Methods: Thirty-two cirrhotic rats were randomly divided into 4 groups. Sham operation (30 min hepatic portal occlusion in sham-operation group and 4 h reperfusion induced HIRI model HIRI group, sodium hydrogen sulfide (H2S donor) preconditioning HIRI model induced Na HS rapamycin RPMN TOR inhibitor) preconditioning The serum levels of aspartate and alanine aminotransferase (alt) were measured after induced by HIRI model. The histopathological changes and autophagy level of liver tissue were observed by light microscope and electron microscope respectively. The expression of LC3-IIand mTOR-phosphorylated m TOR(p-m order protein were detected by Western blot. Results: with the exception of sham operation group, the liver tissues in all groups showed obvious inflammatory reaction, cell swelling and focal necrosis on the basis of liver cirrhosis, but the degree of injury in NaHS group was significantly less than that in HIRI and RPM groups. Compared with the sham-operated group, the alt level in serum of other groups was significantly increased, the number of autophagy in liver cells and the expression of LC3-II protein in liver tissue were significantly increased. The expression of p-m TOR protein and the ratio of p-m TOR/m TOR were significantly decreased (all P 0.05), but the level of transaminase and the number of intracellular macrophages were increased in Na HS group. The increase of LC3-II protein and the decrease of p-m TOR protein in liver tissue were significantly lower than those in HIRI group (P 0.05), but there was no significant difference between RPM group and HIRI group (all P 0.05). Conclusion the preconditioning of W / H _ 2S can alleviate HIRI in cirrhotic rats, and its mechanism may be related to the inhibition of autophagy through activated m TOR pathway.
【作者单位】：湖南省人民医院麻醉科;
【基金】：湖南省科技厅科研条件创新专项立项资助项目(2014TT2019)
【分类号】：R614

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