柚皮素通过激活PPARs对糖尿病肝损伤小鼠的保护作用  

Activation of PPARs is involved in the improvement of naringenin on hepatic injury in diabetic mice

作　　者：薛莱 邱红梅[2] 黄波 罗雯 张昌兰[1] 孟杉杉[1] 杨东 杨志堂 蒋青松[2] Xue Lai;Qiu Hongmei;Huang Bo;Luo Wen;Zhang Changlan;Meng Shasha;Yang Dong;Yang Zhitang;Jiang Qingsong(Department of Clinical Pharmacy,Jiangyou People’s Hospital,Sichuan Jiangyou 621700,China;Department of Pharmacology,School of Pharmacy,Chongqing Medical University,Chongqing 400016,China;Department of Pharmacology,School of Pharmacy,Zunyi Medical University,Zunyi Guizhou 563003,China)

机构地区：[1]江油市人民医院临床药学科,四川江油621700 [2]重庆医科大学药理教研室,重庆市生物化学与分子药理学重点实验室,重庆400016 [3]遵义医科大学基础药理教育部重点实验室暨特色民族药教育部国际合作联合实验室,贵州遵义563003

出　　处：《遵义医科大学学报》2023年第6期568-573,共6页Journal of Zunyi Medical University

基　　金：重庆市自然科学基金资助项目(NO:cstc2017jcy-jAX0211)。

摘　　要：目的探讨柚皮素(NAR)对糖尿病肝损伤小鼠的保护作用及过氧化物酶增殖激活受体(PPARs)的可能作用。方法将昆明小鼠分为正常对照组、糖尿病肝损伤模型组、柚皮素低剂量治疗组(25 mg)及高剂量治疗组(75 mg),每组10只。高脂高糖饲料联合多次小剂量链脲菌素(STZ,40 mg)诱导糖尿病形成后,继续高能量饲料喂养4周,建立糖尿病小鼠肝损伤模型。HE染色观察肝脏形态学改变,生化试剂盒检测小鼠肝功能及血脂水平变化,每周监测空腹血糖(FBG)。利用qRT-PCR和Western blot方法检测肝脏PPARs mRNA和蛋白表达。结果给予STZ 7 d后,小鼠FBG水平持续>11.1 mmol/L。实验结束时模型组小鼠天门冬氨酸氨基转移酶和谷氨酸-丙酮酸转氨酶、总胆固醇和甘油三酯水平均显著增加(P<0.01);病理学检查见肝细胞内脂肪变性,伴炎性细胞浸润;肝脏PPARα、PPARβ及PPARγmRNA和蛋白表达均明显下降(P<0.01)。给予柚皮素治疗4周后,FBG水平较模型组有所降低(P<0.05),仍远高于正常组(P<0.01);血脂水平有所下降(P<0.05);肝功能明显好转(P<0.01),肝组织损伤显著改善;同时,PPARα、PPARβ、PPARγmRNA和蛋白的表达上调(P<0.01)。结论柚皮素对糖尿病肝损伤有保护作用,其作用可能与柚皮素激活PPARs受体有关。Objective The present study is aimed to investigate the effect of naringenin on hepatic injury in diabetic mice and its possible influence on peroxisome proliferators-activated receptors(PPARs)signaling pathway.Methods Male Kunming mice were divided into normal group,diabetic hepatopathy model group and naringenin treatment[intragastric administration at 25 and 75 mg/(kg·d)]groups(n=10).Diabetic hepatopathy model in mice was developed by a high-energy diet combined with streptozotocin[40 mg/(kg·d)].The structure of liver was observed by H.E.staining,and the function of liver was evaluated by blood levels of aspartate aminotransferase(AST)and alanine aminotransferase(ALT).Serum levels of total cholesterol(TCH)and triglyceride(TG)were determined by commercial kits.Fasting blood glucose(FBG)was determined weekly.PPARs mRNA and protein expression were measured respectively by qRT-PCR and Western blotting.Results After 7 days of treatment with streptozotocin,FBG level in mice was above 11.1 mmol/L.At the end of the experiment,the structure of the hepatocytes deformed,including hepatocytes abundant fat vacuoles with filtrating by inflammatory cells,with the increases of AST,ALT,TCH and TG levels in serum(P<0.01).Meanwhile,the expression of PPARα,PPARβand PPARγdecreased at the levels of both mRNA and protein.Compared with the model group,naringenin reduced the FBG(P<0.05),but it was still far higher than the normal mice(P<0.01).Naringenin treatment for 4 weeks markedly improved the structural and functional damage of liver in diabetic mice(P<0.01),and reduced the levels of TCH and TG(P<0.05).Naringenin also up-regulated the expression of PPARα,PPARβand PPARγ(P<0.01).Conclusion Naringenin alleviated hepatic injury in diabetic mice probably via the activation of PPARs signaling pathway.

关 键 词：柚皮素 糖尿病肝损伤 过氧化物酶增殖激活受体 

分 类 号：R587.1[医药卫生—内分泌] R575[医药卫生—内科学]