运动和饮食调整对内质网应激介导非酒精性脂肪肝大鼠模型肝细胞凋亡的影响

发布时间：2019-04-02 03:55

【摘要】：目的:探讨运动和饮食调整对内质网应激介导非酒精性脂肪肝大鼠模型肝细胞凋亡的影响及其机制。方法:70只雄性SD大鼠中随机抽取20只为对照组,其余50只为模型组,对照组予普通饲料喂养,模型组予高脂饲料喂养。实验第8周,对照组和模型组各取10只做肝脏病理切片。确定NAFLD模型成功后,模型组随机分为4组:模型组(M组)、运动组(EM组)、饮食调整组(FM组)和运动结合饮食调整组(EFM组),每组各10只,对照组剩余10只大鼠编为C组。C组继续普通饲料喂养,M组和EM组继续高脂饲料喂养,FM组和EFM组由高脂饲料改为普通饲料喂养;EM组、EFM组给予有氧游泳运动干预,每周运动6 d,每天1次,每次60 min,连续8周,直至第16周实验结束。油红O染色观察肝脏病理形态变化,TUNEL法测肝细胞凋亡,western blot检测C/EBP同源蛋白(CHOP)、C-Jun氨基末端激酶(JNK)和Caspase12蛋白表达,免疫组化检测CHOP、JNK和Caspase12蛋白阳性表达。结果:(1)M组肝细胞脂滴数量显著高于C组,各干预组脂滴数量介于C组和M组之间;(2)M组肝细胞凋亡指数高于C组,CHOP、Caspase12、JNK蛋白表达及阳性表达较C组高;各干预组肝细胞凋亡指数低于M组,CHOP、Caspase12、JNK蛋白表达及阳性表达较M组低;(3)M组、EM组、FM组、EFM组4组双因素方差结果示:运动和饮食对CHOP、Caspase12、JNK蛋白表达具有主效应,且二者具有叠加交互效应。结论:内质网应激介导细胞凋亡参与NAFLD的发展,运动和饮食调整可延缓NAFLD的发展,且二者联合作用效果更佳,其机制与运动和饮食调整降低内质网应激介导细胞凋亡蛋白CHOP、JNK和Caspase12在肝细胞的表达,抑制肝细胞凋亡有关。
[Abstract]:Aim: to investigate the effects of exercise and diet adjustment on hepatocyte apoptosis in rats with nonalcoholic fatty liver induced by endoplasmic reticulum stress. Methods: 20 of 70 male SD rats were randomly selected as the control group, the other 50 rats were the model group, the control group was fed with ordinary diet and the model group was fed with high fat diet. At the 8th week of the experiment, 10 rats in the control group and the model group were taken for pathological sections of the liver. After confirming the success of NAFLD model, the model group was randomly divided into 4 groups: model group (M group), exercise group (EM group), diet adjustment group (FM group) and exercise combined diet adjustment group (EFM group), 10 rats in each group. The remaining 10 rats in the control group were divided into group C, group M and EM, and group FM and EFM from high fat diet to normal diet, and the other 10 rats were divided into two groups: group C (n = 10), group C (n = 10). The EM group and EFM group were given aerobic swimming intervention for 6 days a week once a day for 60 min, for 8 weeks until the end of the experiment in the 16th week. The pathological changes of liver were observed by oil red O staining. The expression of C/EBP homologue protein (CHOP), C-Jun N terminal kinase (JNK) and Caspase12 protein was detected by TUNEL method, and the expression of CHOP,JNK and Caspase12 protein was detected by immunohistochemistry. Results: (1) the number of lipid droplets in M group was significantly higher than that in C group, and the number of lipid droplets in each intervention group was between C group and M group, (2) the apoptosis index of hepatocytes in M group was higher than that in C group, and the expression and positive expression of CHOP,Caspase12,JNK protein was higher than that in C group. The apoptosis index of hepatocytes in each intervention group was lower than that in M group, and the expression and positive expression of CHOP,Caspase12,JNK protein were lower than those in M group. (3) the results of two-way ANOVA of M group, EM group, FM group and EFM group showed that exercise and diet had the main effect on the expression of CHOP,Caspase12,JNK protein, and there was superimposed interaction effect between the two groups. Conclusion: apoptosis induced by endoplasmic reticulum stress is involved in the development of NAFLD. Exercise and diet adjustment can delay the development of NAFLD, and the effect of combination of exercise and diet is better. The mechanism and diet regulation can reduce the apoptosis protein CHOP, induced by endoplasmic reticulum stress. The expression of JNK and Caspase12 in hepatocytes is related to the inhibition of hepatocyte apoptosis.
【作者单位】：成都体育学院运动医学系;北京体育大学研究生院;
【基金】：“十二五”国家科技支撑计划重点项目子课题(2012BAK21B01-4) 四川省科技厅应用基础计划项目(2015JY0155) 国家体育总局运动医学重点实验室暨运动医学四川省重点实验室资助基金(CTYY2015018)
【分类号】：R575.5

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