大黄通过改善线粒体自噬缓解急性胰腺炎大鼠内质网应激和脂质代谢障碍的机制  

Rhubarb alleviates endoplasmic reticulum stress and lipid metabolism disorder in rats with acute pancreatitis by improving mitochondrial autophagy

作　　者：张宁 王玲玲 邓雍 郭文成[1] 王芳[1] ZHANG Ning;WANG Ling-ling;DENG Yong(Department of Gastroenterology,Yulin Second Hospital,Yulin Shaanxi 719000,China;Department of Gastroenterology,215 Hospital of Nuclear Industry of Shaanxi Province,Xianyang Shaanxi 712000,China;Department of Critical Care Medicine,Yulin First Hospital,Yulin Shaanxi 719000,China)

机构地区：[1]榆林市第二医院消化内科,陕西榆林719000 [2]陕西省核工业二一五医院消化内科,陕西咸阳712000 [3]榆林市第一医院重症医学科,陕西榆林719000

出　　处：《临床和实验医学杂志》2021年第7期687-691,共5页Journal of Clinical and Experimental Medicine

基　　金：陕西省科技计划项目(编号:2017K17-2-09-65)。

摘　　要：目的探讨大黄通过改善线粒体自噬缓解急性胰腺炎大鼠内质网应激和脂质代谢障碍的机制。方法选取100只SD大鼠,按随机数字表法分为空白对照组、模型组、大黄低(0.5 mL/kg)、中(1.0 mL/kg)、高(2.0 mL/kg)剂量组,每组20只,除空白对照组其余各组均构建急性胰腺炎模型。蛋白质印迹法检测线粒体自噬相关蛋白[微管相关蛋白1轻链3-Ⅰ(LC3-Ⅰ)、微管相关蛋白1轻链3-Ⅱ(LC3-Ⅱ)和自噬相关蛋白5(ATG5)]、内质网应激相关蛋白[磷酸化α亚基的真核起始因子2(p-eIF2α)、葡萄糖调节蛋白78(GRP78)以及转录因子C/EBP同源蛋白(CHOP)]的表达。全自动生化分析仪测定各组大鼠总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)水平;酶联免疫吸附试验(ELISA)法检测超氧化物歧化酶(SOD)、丙二醛(MDA)和谷胱甘肽(GSH)水平以及炎性因子白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α)水平。结果与空白对照组比较,模型组大鼠线粒体自噬相关蛋白(LC3-Ⅰ、LC3-Ⅱ和ATG5)和内质网应激相关蛋白(p-eIF2α、GRP78、CHOP)相对表达量显著升高,差异均有统计学意义(P<0.05);与模型组比较,大黄低、中、高剂量组大鼠线粒体自噬相关蛋白和内质网应激相关蛋白相对表达量均显著降低,差异均有统计学意义(P<0.05)。与空白对照组比较,模型组大鼠TC、TG、LDL-C、MDA、IL-6、IL-1β、TNF-α水平均显著升高,HDL-C、SOD和GSH水平显著降低,差异均有统计学意义(P<0.05);与模型组比较,大黄低、中、高剂量组大鼠TC、TG、LDL-C、MDA、IL-6、IL-1β、TNF-α水平显著降低,HDL-C、SOD和GSH水平显著增加,差异均有统计学意义(P<0.05),且大黄的作用呈剂量依赖性。结论大黄能够通过改善线粒体自噬来缓解急性胰腺炎大鼠内质网应激和脂质代谢障碍水平,且2.0 mL/kg的大黄效果最佳。Objective To investigate the mechanism of Rhubarb in relieving endoplasmic reticulum stress and lipid metabolism disorder in rats with acute pancreatitis by improving mitochondrial autophagy.Methods One hundred SD rats were selected and divided into blank control group,model group,rhubarb low(0.5 mL/kg),medium(1.0 mL/kg),and high(2.0 mL/kg)dose groups according to the random number table method,20 cases in each group.Acute pancreatitis model was constructed in all groups except blank control group.The automatic biochemical analyzer was used to determine the levels of total cholesterol(TC),triglycerides(TG),high density lipoprotein cholesterol(HDL-C),and low density lipoprotein cholesterol(LDLC)in each group of rats.The levels of superoxide dismutase(SOD),malondialdehyde(MDA)and glutathione(GSH)and the inflammatory cytokine interleukin-6(IL-6),interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)were detected by enzyme-linked immunosorbent assay(ELISA).The expression of mitophagy-related protein[light chain 3-Ⅰ(LC3-Ⅰ),light chain 3-Ⅱ(LC3-Ⅱ),autophagy-related protein 5(ATG5)],endoplasmic reticulum stress-related protein[phosphorylationαsubunit eukaryotic initiation factor 2(p-eIF2α),glucose regulatory protein 78(GRP78),C/EBP-homologous protein(CHOP)]were detected by Western blotting.Results Compared with the blank control group,the relative expression of mitochondrial autophagy-related proteins(LC3-Ⅰ,LC3-Ⅱ,and ATG5)and endoplasmic reticulum stress-related proteins(p-eIF2α,GRP78,CHOP)in the model group increased significantly,the differences were statistically significant(P<0.05);Compared with the model group,the relative expression of mitochondrial autophagy-related protein and endoplasmic reticulum stress-related protein in the low,medium and high dose groups of rhubarb reduced significantly,the differences were statistically significant(P<0.05).Compared with the blank control group,the levels of TC,TG,LDL-C,MDA,IL-6,IL-1β,and TNF-αin the model group increased significantly,and the levels of

关 键 词：大鼠 大黄 线粒体自噬 急性胰腺炎 内质网应激 脂质代谢障碍 

分 类 号：R285.5[医药卫生—中药学]