下调miR-122对非酒精性脂肪性肝炎小鼠的炎症发生及肝细胞凋亡的影响  

Effect of down-regulating miR-122 on inflammation and hepatocyte apoptosis in non-alcoholic steatohepatitis mice

作　　者：谢景军[1] 魏从光[2] 张建峰[3] 孙常青 王怀志[1] XIE Jingjun;WEI Congguang;ZHANG Jianfeng;SUN Changqing;WANG Huaizhi(Department of General Surgery,Armed Police Henan Corps Hospital,Zhengzhou 450002,China;Department of Gastroenterology,Armed Police Henan Corps Hospital,Zhengzhou 450002,China;Department of Health Service,Armed Police Henan Corps Hospital,Zhengzhou 450002,China)

机构地区：[1]武警河南总队医院普通外科,河南郑州450002 [2]武警河南总队医院内二科消化内科病区,河南郑州450002 [3]武警河南总队医院卫勤处,河南郑州450002

出　　处：《胃肠病学和肝病学杂志》2020年第8期873-878,共6页Chinese Journal of Gastroenterology and Hepatology

摘　　要：目的探讨下调miR-122对非酒精性脂肪性肝炎(non-alcoholic steatohepatitis, NASH)小鼠的炎症发生及肝细胞凋亡的影响。方法 qRT-PCR检测各组小鼠肝组织中miR-122的表达情况;HE染色观察各组小鼠肝组织病理损伤情况;油红O染色观察各组小鼠肝组织脂肪堆积情况;ELISA检测各组小鼠血清中甘油三脂(TG)、丙氨酸转氨酶(ALT)、天门冬氨酸转氨酶(AST)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)和白细胞介素-6(IL-6)的表达情况;TUNEL荧光染色观察各组小鼠肝细胞凋亡情况;Western blotting检测各组小鼠肝组织中Bax、Bcl-2蛋白表达水平。结果 miR-122 mRNA的表达水平在MCD组和MCD+miR-NC组小鼠肝组织中表达水平上调(P均<0.01),在MCD+miR-122 inhibitor组小鼠肝组织中表达水平下调(P<0.001);MCD组和MCD+miR-NC组小鼠的肝脏出现中度至重度肝细胞空泡化和大量脂质滴(P均<0.001),MCD+miR-122 inhibitor组小鼠的肝脏组织表现出轻度至中度的肝细胞空泡和脂质滴也减少(P<0.05);MCD组和MCD+miR-NC组小鼠血清中TG、ALT、AST、TNF-α、IL-1β和IL-6表达水平上调(P均<0.01),MCD+miR-122 inhibitor组小鼠血清中TG、ALT、AST、TNF-α、IL-1β和IL-6表达水平下调(P均<0.05);MCD组和MCD+miR-NC组肝细胞凋亡指数升高(P均<0.001),MCD+miR-122 inhibitor组肝细胞凋亡指数下降(P<0.05);MCD组和MCD+miR-NC组小鼠肝组织中Bax蛋白表达水平上调(P<0.01),Bcl-2蛋白表达下调(P均<0.001),MCD+miR-122 inhibitor组小鼠肝组织中Bax蛋白表达水平下调(P<0.05),Bcl-2蛋白表达上调(P<0.05)。结论下调miR-122可抑制炎症的发生、抑制肝细胞凋亡,对NASH有一定的治疗作用。Objective To investigate the effect of down-regulating miR-122 on inflammation and hepatocyte apoptosis in non-alcoholic steatohepatitis(NASH) mice. Methods qRT-PCR was used to detect the expression of miR-122 in liver tissue of mice in each group;HE staining was used to observe the pathological damage of liver tissue of mice in each group. Oil red O staining was used to observe the fat accumulation of liver tissue of mice in each group;ELISA was used to detecte serum triglyceride(TG), alanine transaminase(ALT), aspartate aminotransferase(AST), tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β) and interleukin-6(IL-6) expression;TUNEL fluorescence staining was used to observe the apoptosis of liver cells of mice in each group;Western blotting was used to detect the changes of Bax and Bcl-2 protein expression in liver tissue of mice in each group. Results The expression level of miR-122 in liver tissue of MCD group and MCD+miR-NC group was up-regulated(both P<0.01), and the expression level of liver tissue in MCD+miR-122 inhibitor group was down-regulated(P<0.001);MCD group and MCD+miR-NC group mice showed moderate to severe hepatocyte vacuolation and a large number of lipid droplets(both P<0.001), the liver tissue of MCD+miR-122 inhibitor group mice showed mild to moderate hepatocyte vacuoles and lipid droplets(P<0.05). The levels of TG, ALT, AST, TNF-α, IL-1β, and IL-6 in the serum of mice in MCD group and MCD+miR-NC group were up-regulated(all P<0.01), the levels of TG, ALT, AST, TNF-α, IL-1β and IL-6 in the serum of mice in MCD+miR-122 inhibitor group were down-regulated(all P<0.05);MCD group and MCD+miR-NC group increased hepatocyte apoptosis index(both P<0.001), while MCD+miR-122 inhibitor group decreased hepatocyte apoptosis index(P<0.05);MCD group and MCD+miR-NC group mice liver tissue Bax protein expression level was up-regulated(P<0.01), Bcl-2 protein expression was down-regulated(both P<0.001). The expression level of Bax protein was down-regulated(P<0.05), and the expression of Bcl-2 protein

关 键 词：MIR-122 非酒精性脂肪性肝炎 炎症 凋亡 

分 类 号：R575.5[医药卫生—消化系统]