肝脏生物钟紊乱对CG-IUGR大鼠糖尿病高易感的可能作用  

Study on the possible role of hepatic circadian clock disturbance played in the high susceptibility to DM of CG-IUGR rats

作　　者：袁冰舒 杜运松 李丽娟 Yuan Bingshu;Du Yunsong;Li Lijuan(Department of Pathophysiology,Zunyi Medical University,Zunyi Guizhou,563099,China;Department of Pathology,Jieshou City People’s Hospital,Jieshou Anhui 236500,China)

机构地区：[1]遵义医科大学病理生理学教研室,贵州遵义563099 [2]界首市人民医院病理科,安徽界首236500

出　　处：《遵义医科大学学报》2023年第2期114-120,共7页Journal of Zunyi Medical University

基　　金：国家自然科学基金资助项目(NO:82260314);贵州省科学技术基金资助项目(NO:黔科合基础[2019]1336)。

摘　　要：目的 通过检测肝脏生物钟基因BMAL1、CLOCK的表达及糖代谢功能的状态,分析生物钟改变与CG-IUGR大鼠糖尿病高易感之间的可能关系。方法 实验分为Control组及CG-IUGR组。通过低热量饮食法建立CG-IUGR大鼠模型,正常饲养大鼠则为Control组。观测两组大鼠出生至8周龄的身长、体重,并由此计算其体重指数,测量8周龄大鼠肾周脂肪组织的重量。比较两组大鼠糖代谢的功能:包括检测空腹血糖(FBG)和血清胰岛素(FINS)水平,进行葡萄糖耐量实验(GTT)及胰岛素耐量实验(ITT),检测葡萄糖负荷15 min的血清胰岛素(INS)水平;采用生化方法检测肝脏GS酶活性;采用Western blot方法检测肝脏BMAL1、CLOCK的蛋白表达;采用Pearson’s法分析肝脏BMAL1、CLOCK的蛋白相对表达水平与CG-IUGR大鼠葡萄糖负荷后15 min的血糖和血清INS水平及肝脏GS酶活性的相关性。结果 在生长发育过程中CG-IUGR大鼠的身长、体重和BMI均增高;其8周龄肾周的脂肪重量亦增加(P<0.05)。CG-IUGR大鼠8周龄时,FBG无明显异常,FINS水平轻度下调(P<0.05);血糖水平在糖负荷和INS负荷后均明显上调(P<0.05),且血清INS水平在糖负荷15 min后显著上调(P<0.05);肝脏GS酶活性降低(P<0.05);同时BMAL1和CLOCK的蛋白表达均下调(P<0.05)。CG-IUGR大鼠肝脏BMAL1、CLOCK的蛋白相对表达水平与葡萄糖负荷后15 min的血糖和血清INS水平均呈负相关性,与肝脏GS酶活性呈正相关性(P<0.05)。结论 CG-IUGR大鼠糖代谢功能降低,对DM的易感性增加;CG-IUGR大鼠对DM的易感性增加可能与IUGR下调肝脏生物钟基因BMAL1、CLOCK的表达有关。Objective This study is to analyze the possible relationship between the changes of circadian clock and abnormal glucose metabolism in CG-IUGR rats. Methods Rats were divided into control(normal rats) and CG-IUGR groups. CG-IUGR rat model was established by low-calorie diet. The growth and development of rats in the two groups(body length, body weight and body mass index(BMI) at 0 to 8 weeks) were detected, and their perirenal fat was weighed. The function of glucose metabolism was assessed by detecting the levels of fasting blood glucose(FBG) and fasting insulin(FINS) and serum insulin(INS) at the 15 minutes after glucose load, with the glucose tolerance test(GTT) and insulin tolerance test(ITT) being carried out. The activity of hepatic glycogen synthase(GS) was detected by biochemical methods. The protein expression of BMAL1 and CLOCK in hepatic tissue were determined by Western blot. Pearson’s correlation coefficient was used to analyze the correlation between the relative expression levels of hepatic BMAL1 and CLOCK proteins and the blood glucose and serum INS levels at the 15 minutes after glucose loading in CG-IUGR rats, and the same method was used to analyze the correlation between these protein expression levels and hepatic GS enzyme activity. Results The body length, body weight and BMI of CG-IUGR rats were increased in the process of growth and development(P<0.05). Compared with control group, the perirenal fat weight of CG-IUGR group was markedly increased(P<0.05). Compared with control group, the FBG levels of CG-IUGR group were no significant change, while the FINS levels were decreased mildly(P<0.05). Compared with control group, the blood glucose levels of CG-IUGR group after glucose and INS load were increased at all time point(P<0.05), and the serum INS levels after glucose load 15 minutes were also increased significantly(P<0.05). Compared with control group, the hepatic GS enzyme activity of CG-IUGR group was decreased(P<0.05), the protein expression of hepatic BMAL1 and CLOCK in CG-IUGR gr

关 键 词：糖尿病 IUGR BMAL1 CLOCK 糖原合成酶 

分 类 号：R363[医药卫生—病理学]