有氧运动对非酒精性脂肪肝小鼠肝脏CNPY2-PERK通路的影响*

目的: 探讨有氧运动对高脂诱导小鼠非酒精性脂肪肝(NAFLD)的影响及其肝脏冠层成纤维细胞生长因子信号调节器 2 (CNPY2) - PKR样内质网激酶(PERK)机制。方法: 8周龄雄性C57BL/6J小鼠随机分为对照组(C)、对照+运动组(CE),NAFLD模型组(M)和NAFLD模型+运动组(ME),每组10只。C组和CE组小鼠给予普通饲料,M组和ME组小鼠给予高脂饲料(脂肪供能占比为60 %),连续喂养18周至实验结束,取小鼠血清和肝脏。CE组和ME组从第10周起进行有氧跑台训练(12 m/min,每次60 min,每周5 d)。检测小鼠血清总胆固醇(TC)、总甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-c)、低密度脂蛋白胆固醇(LDL-c)、丙氨酸氨基转移酶(ALT)和天冬氨酸转氨酶(AST)水平;观察小鼠肝组织病理学形态;检测肝组织CNPY2、PERK、p-eIF2a、CHOP、CNPY2 mRNA、PERK mRNA表达和CNPY2、PERK的阳性表达。结果: 与C组比较,M 组小鼠的血清LDL-c、TC、TG、ALT和AST水平显著升高(P＜0.05),HDL-c水平显著降低(P＜0.05);小鼠肝组织可见明显的肝脂肪性变,肝细胞脂滴数量增加,肝组织的CNPY2、CNPY2 mRNA、PERK、PERK mRNA、p-eIF2a、CHOP表达、CNPY2和PERK阳性表达均显著升高(P＜0.05);而CE组的上述指标均没有显著性差异(P＞0.05 )。与M 组比较,ME组小鼠的血清LDL-c、TC、TG、ALT和AST水平显著降低(P＜0.05),小鼠肝组织脂肪性变明显减轻,肝细胞脂滴数量显著减少,肝组织的CNPY2、CNPY2 mRNA、PERK、PERK mRNA、p-eIF2a、CHOP表达、CNPY2和PERK阳性表达均显著降低(P＜ 0.05)。结论: 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。

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

Objective: To investigate the effects of aerobic exercise on non-alcoholic fatty liver (NAFLD) induced by high fat and the mechanism of CNPY2-PERK pathway. Methods: 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. Results: Compared with group C, the serum levels of LDL-c, TC, TG, ALT and AST in group M were increased significantly (P＜0.05), while the HDL-c level was decreased significantly (P＜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 (P＜0.05). However, the above indexes showed no significant difference in CE group (P＞0.05). Compared with group M, the serum levels of LDL-c, TC, TG, ALT and AST in group ME were decreased (P＜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 (P＜0.05). Conclusion: 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.