肿瘤坏死因子相关蛋白6缺失减缓CCl4诱发的小鼠肝脏纤维化进程

基础医学与临床 ›› 2021, Vol. 41 ›› Issue (12): 1736-1741.

肿瘤坏死因子相关蛋白6缺失减缓CCl₄诱发的小鼠肝脏纤维化进程

蔡欢嫦, 周丹茹, 史天静, 尹亚军, 张大伟^*, 张瑾^*

嘉兴学院生物与化学工程学院,浙江嘉兴 314001

收稿日期:2020-09-11 修回日期:2021-05-10 发布日期:2021-12-03
通讯作者: *weixiaozdw@126.com;zhangjin7688@163.com
基金资助:
浙江省自然科学基金(LY20C170003);嘉兴学院校级SRT计划(8517193163);嘉兴学院科研启动经费(70518061)

CTRP6 deficiency alleviates CCl₄-induced liver fibrosis progression in mice

CAI Huan-chang, ZHOU Dan-ru, SHI Tian-jing, YIN Ya-jun, ZHANG Da-wei^*, ZHANG Jin^*

College of Biological, Chemical Science and Engineering, Jiaxing University, Jiaxing 314001,China

Received:2020-09-11 Revised:2021-05-10 Published:2021-12-03
Contact: *weixiaozdw@126.com;zhangjin7688@163.com

摘要/Abstract

摘要： 目的探讨补体Clq/肿瘤坏死因子相关蛋白6(CTRP6)在肝病发生发展中的作用及其可能机制。方法四氯化碳灌胃法构建小鼠肝纤维化模型,比较野生型(CTRP6^+/+)和敲除型(CTRP6^-/-)小鼠肝损伤后的病理和生化指标差异;RT-qPCR检测纤维化标志基因(Acta2、Col1a1、Mmp2、TGF-β和TNF-α)和细胞增殖标志基因(Cyclin D、Cyclin E和CDK6)的表达水平。结果与CTRP6^+/+小鼠相比,CTRP6^-/-小鼠肝细胞表现为轻度的坏死、疏松和肿胀等病变,且肝内超氧化物歧化酶(SOD)活力升高(P＜0.01)、丙二醛(MDA)含量降低(P＜0.01);CTRP6^-/-小鼠肝脏纤维化和细胞增殖标志基因表达显著低于CTRP6^+/+小鼠。结论 CTRP6基因缺失减缓了CCl₄诱导的小鼠肝纤维化进程,作用机制可能是敲除CTRP6影响了肝细胞的增殖。

关键词: 补体Clq/肿瘤坏死因子相关蛋白6(CTRP6), 肝纤维化, 四氯化碳, 基因表达

Abstract: Objective To explore the role and underlying mechanism of C1q/TNF-related protein 6 (CTRP6) in the development process of liver disease. Methods The histopathological examination and biochemical indexes of injured livers from wild-type (CTRP6^+/+) and knockout (CTRP6^-/-) mice induced by intragastric administration of CCl₄ were analyzed. RT-qPCR was used to detect the expression of the fibrosis marker genes (Acta2, Col1al, Mmp2 and TGF-β) and cell proliferation marker genes (Cyclin D, Cyclin E and CDK6). Results Compared with CTRP6^+/+ mice, the hepatocytes in CTRP6^-/- mice showed mild necrosis, looseness and swelling. The high SOD activity and low MDA level were also observed in CTRP6^-/- mice liver. Meanwhile, the expression of fibrosis and cell proliferation markers in CTRP6^-/- mice were significantly lower than those in CTRP6^+/+ mice. Conclusions CTRP6 gene is closely related to liver disease development, and the liver fibrosis progression induced by CCl₄ is alleviated by its deletion. The mechanism may be explained as that CTRP6 knockout affects the proliferative capacity of hepatocytes.

Key words: C1q/TNF-related protein 6 (CTRP6), liver fibrosis, carbon tetrachloride (CCl₄), gene expression

中图分类号:

R394-3

蔡欢嫦, 周丹茹, 史天静, 尹亚军, 张大伟, 张瑾. 肿瘤坏死因子相关蛋白6缺失减缓CCl₄诱发的小鼠肝脏纤维化进程[J]. 基础医学与临床, 2021, 41(12): 1736-1741.

CAI Huan-chang, ZHOU Dan-ru, SHI Tian-jing, YIN Ya-jun, ZHANG Da-wei, ZHANG Jin. CTRP6 deficiency alleviates CCl₄-induced liver fibrosis progression in mice[J]. Basic & Clinical Medicine, 2021, 41(12): 1736-1741.

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肿瘤坏死因子相关蛋白6缺失减缓CCl₄诱发的小鼠肝脏纤维化进程

CTRP6 deficiency alleviates CCl₄-induced liver fibrosis progression in mice

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