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有氧运动对非酒精性脂肪性肝病小鼠肝脏中CNPY2-PERK通路的影响

[Effects of aerobic exercise on CNPY2-PERK pathway in the liver of mice with non-alcoholic fatty liver disease].

作者信息

Li Jun-Han, Xiong Wei, Wang Jia-Qian, Li Ya-Long, Jiang Chang-Jun

机构信息

College of Sports Medicine and Health, Chengdu Sports University, Chengdu 610041.

Department of Hepatobiliary Surgery, Sichuan Provincial Hospital, Chengdu 610041, China.

出版信息

Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2022 Sep;38(3):193-198. doi: 10.12047/j.cjap.6282.2022.046.

Abstract

To investigate the effects of aerobic exercise on non-alcoholic fatty liver (NAFLD) induced by high fat and the mechanism of CNPY2-PERK pathway. Eight-week-old male C57BL/6J mice were randomly divided into four groups: the control group (C), the C+ aerobic exercise group (CE), the model group (M) and the M+ aerobic exercise group (ME). Mice in group C and CE were given normal diet, while mice in group M and ME were given high-fat diet (60 cal % fat). The mice were fed continuously for 18 weeks until the end of the experiment, and the serum and liver samples were collected. Both CE and ME group performed an aerobic treadmill training from the 10th week (12 m/min, 60 min/ day, 5 days/week, for 8 weeks). The serum levels of total cholesterol (TC), triacylglycerol (TG), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), alanine aminotransferase (ALT), aspartate aminotransferase (AST) were detected. The pathological morphology of the liver was observed. The relative expressions of CNPY2, PERK, p-eIF2a, CHOP, CNPY2 mRNA and PERK mRNA, and the positive expressions of CNPY2 and PERK were measured. Compared with group C, the serum levels of LDL-c, TC, TG, ALT and AST in group M were increased significantly (<0.05), while the HDL-c level was decreased significantly (<0.05). The liver tissues of mice showed obvious hepatic steatosis, the number of lipid droplets in liver cells was increased, and the expressions of CNPY2, CNPY2mRNA, PERK, PERKmRNA, p-eIF2a, CHOP, and the positive expressions of both CNPY2 and PERK in liver were increased (<0.05). However, the above indexes showed no significant difference in CE group (>0.05). Compared with group M, the serum levels of LDL-c, TC, TG, ALT and AST in group ME were decreased (<0.05). The fatty degeneration of liver tissue and the number of lipid droplets in liver cells in mice was reduced, and the expressions of CNPY2, CNPY2 mRNA, PERK, PERK mRNA, p-eIF2a, CHOP, and the positive expressions of CNPY2 and PERK in liver tissue were decreased (<0.05). The CNPY2-PERK pathway is involved in the formation of NAFLD. Aerobic exercise can effectively ameliorate NAFLD, and the mechanisms may be related to the reduction of CNPY2-PERK pathway-related molecule expressions by aerobic exercise.

摘要

探讨有氧运动对高脂诱导的非酒精性脂肪肝(NAFLD)的影响及CNPY2-PERK通路的作用机制。将8周龄雄性C57BL/6J小鼠随机分为四组:对照组(C)、C+有氧运动组(CE)、模型组(M)和M+有氧运动组(ME)。C组和CE组小鼠给予正常饮食,M组和ME组小鼠给予高脂饮食(脂肪含量60千卡%)。持续喂养小鼠18周直至实验结束,收集血清和肝脏样本。CE组和ME组从第10周开始进行有氧跑步机训练(12米/分钟,每天60分钟,每周5天,共8周)。检测血清总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-c)、低密度脂蛋白胆固醇(LDL-c)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)水平。观察肝脏病理形态。检测CNPY2、PERK、p-eIF2a、CHOP、CNPY2 mRNA和PERK mRNA的相对表达以及CNPY2和PERK的阳性表达。与C组相比,M组血清LDL-c、TC、TG、ALT和AST水平显著升高(<0.05),而HDL-c水平显著降低(<0.05)。小鼠肝脏组织呈现明显的肝脂肪变性,肝细胞内脂滴数量增加,肝脏中CNPY2、CNPY2mRNA、PERK、PERKmRNA、p-eIF2a、CHOP的表达以及CNPY2和PERK的阳性表达均增加(<0.05)。然而,CE组上述指标无显著差异(>0.05)。与M组相比,ME组血清LDL-c、TC、TG、ALT和AST水平降低(<0.05)。小鼠肝脏组织脂肪变性及肝细胞内脂滴数量减少,肝脏组织中CNPY2、CNPY2 mRNA、PERK、PERK mRNA、p-eIF2a、CHOP的表达以及CNPY2和PERK的阳性表达均降低(<0.05)。CNPY2-PERK通路参与NAFLD的形成。有氧运动可有效改善NAFLD,其机制可能与有氧运动降低CNPY2-PERK通路相关分子表达有关。

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