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目的探讨大鼠非酒精性脂肪肝病(NAFLD)模型中利拉鲁肽对炎症反应和抗氧化能力的影响及对脂类代谢相关酶的表达调控。方法 SD大鼠70只,25只给予正常饮食,45只采用高糖饮食加高脂灌胃12周,正常组和模型组随机挑取5只大鼠处死。确定NAFLD模型成功建立后,随机分为空白对照组(n=20)、模型对照组(n=20)和利拉鲁肽治疗组(n=20)。利拉鲁肽治疗组给予利拉鲁肽60μg/(kg·d)皮下注射,模型对照组给予生理盐水1ml/(kg·d)皮下注射。利拉鲁肽治疗开始4周和8周后,各组处死大鼠各半,测定各组血浆中炎性因子、氧化因子、抗氧化因子、肝功能和脂类的变化,检测肝脏的形态学改变,采用反转录聚合酶链反应(RT-PCR)检测胆固醇调节元件结合转录因子-1c(SREBF-1c)和乙酰辅酶A羧化酶α(ACCα)的mRNA表达,应用免疫组织化学和Western blotting检测SREBF-1c和ACCα的蛋白质表达。结果与模型对照组比较,利拉鲁肽治疗4周和8周后,血浆中C反应蛋白(CRP)、白细胞介素(IL)-1α、IL-1β、IL-6、肿瘤坏死因子-α(TNF-α)、丙二醛(MDA)、天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、甘油三酯(TG)、总胆固醇(TC)和低密度脂蛋白胆固醇(LDL-C)含量降低(P<0.05);超氧化物歧化酶(SOD)、谷胱甘肽(GSH)和总抗氧化能力(T-AOC)增加(P<0.05),肝脏组织脂肪颗粒沉积减少;肝脏组织中SREBF-1c和ACCα的mRNA和蛋白表达下调(P<0.05)。利拉鲁肽治疗8周与治疗4周比较,上述指标进一步改善。结论利拉鲁肽可以减轻NAFLD中炎症反应,提高抗氧化能力,改善肝功能;利拉鲁肽可能通过下调肝脏组织中SREBF-1c和ACCα的表达,减少脂质的生成,缓解肝脏组织中的脂肪变性,而且随治疗时间的增加,对NAFLD的防治作用更明显。
Objective To investigate the effects of liraglutide on inflammatory reaction and antioxidant capacity in rat model of non-alcoholic fatty liver disease (NAFLD) and to study the regulation of lipid metabolism-related enzymes. Methods Seventy-two SD rats were fed with normal diet. Forty-five rats were given high-carbohydrate diet and high-fat gavage for 12 weeks. Five rats were killed randomly in normal group and model group. After establishing the NAFLD model successfully, the rats were randomly divided into blank control group (n = 20), model control group (n = 20) and liraglutide treatment group (n = 20). The liraglutide treatment group was given liraglutide 60 μg / (kg · d) subcutaneously, and the model control group was injected subcutaneously with normal saline 1 ml / (kg · d). At 4 and 8 weeks after the initiation of liraglutide treatment, rats in each group were sacrificed in half to determine the change of plasma inflammatory and oxidative factors, antioxidants, liver function and lipid in each group, and the morphology of liver (SREBF-1c) and acetyl-CoA carboxylase α (ACCα) mRNA were detected by reverse transcriptase polymerase chain reaction (RT-PCR). Immunohistochemistry and Western blotting was used to detect the protein expression of SREBF-1c and ACCα. Results Compared with the model control group, plasma C-reactive protein (CRP), interleukin (IL) -1α, IL-1β, IL-6 and tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglyceride (TG), total cholesterol (TC) (P <0.05); the activities of superoxide dismutase (SOD), glutathione (GSH) and total antioxidative capacity (T-AOC) increased The deposition of fat particles decreased. The mRNA and protein expressions of SREBF-1c and ACCα in liver tissues were decreased (P <0.05). The above indicators were further improved when liraglutide treatment for 8 weeks compared with 4 weeks for treatment. Conclusion Liraglutide can reduce the inflammatory response in NAFLD, improve the anti-oxidative capacity and improve the liver function. Liraglutide may reduce the production of lipids and reduce the expression of SREBF-1c and ACCα in the liver tissue Steatosis, and with the increase of treatment time, the prevention and treatment of NAFLD is more obvious.