参芪复方调控糖尿病GK大鼠肝脏circRNA表达谱改善糖脂代谢的作用机制  

Mechanism of Shenqi Compound in improving glucolipid metabolism by regulating circRNA expression profile in liver of diabetic GK rats

作　　者：彭思涵 刘桠[2] 谢春光[1,2] 张翕宇 陈秋[2] PENG Si-han;LIU Ya;XIE Chun-guang;ZHANG Xi-yu;CHEN Qiu(TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province,Hospital of Chengdu University of TCM,Chengdu 610075,China;Department of Endocrindogy,Hospital of Chengdu University of TCM,Chengdu 610075,China)

机构地区：[1]成都中医药大学附属医院代谢性疾病中医药调控四川省重点实验室,成都610075 [2]成都中医药大学附属医院内分泌科,成都610075

出　　处：《中华中医药杂志》2023年第5期2418-2423,共6页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：四川省博士后创新人才支持项目(No.BX202205);四川省科技创新苗子工程(No.2022036);成都中医药大学附属医院院基金项目(No.22HL02)。

摘　　要：目的:探讨参芪复方调控糖尿病GK大鼠肝脏circRNA表达谱改善糖脂代谢的作用机制。方法:采用高脂高糖饲料诱导2型糖尿病模型,将糖尿病GK大鼠随机分为模型组、参芪复方组和西格列汀组,另设10只Wistar大鼠为空白组。干预12周,检测空腹血糖(FPG)、空腹胰岛素(FINS)、血脂及肝功能,计算胰岛素抵抗指数(HOMA-IR),通过HE染色观察肝脏病理变化,收集肝脏样本进行circRNA测序并分析差异基因生物学功能。结果:与空白组比较,糖尿病GK大鼠FPG显著升高(P<0.01,P<0.05),模型组大鼠FINS、HOMA-IR显著升高(P<0.01),血脂及肝功能有不同程度升高(P<0.01,P<0.05),肝脏可见病理改变。与模型组比较,治疗12周后参芪复方组大鼠FPG、FINS及HOMA-IR均显著下降(P<0.05,P<0.01),血脂(P<0.01,P<0.05)、肝功能及肝脏病理有所缓解。参芪复方对176个circRNA具有逆向调节功能,其主要差异circRNA host基因聚集在以内分泌系统、脂质代谢等糖脂代谢信号通路为核心的功能聚类。结论:参芪复方可能通过广泛调控circRNA的差异表达及下游相关信号通路以调节糖脂代谢紊乱、改善肝脏病理损伤。Objective:To explore the mechanism of Shenqi Compound regulating circRNA expression profile in liver of diabetic GK rats in order to improve glucolipid metabolism.Methods:Type 2 diabetes model were prepared by high fat and high sugar diet,and these rats were randomly divided into model group,Shenqi Compound group and Sitagliptin group.While 10 Wistar rats were set as blank group.After 12 weeks of intervention,fasting plasma glucose(FPG),fasting insulin(FINS),blood lipid and liver function levels of each group were detected,insulin resistance index(HOMA-IR)was calculated,and pathological changes of liver were observed by HE staining.Liver samples were collected for circRNA sequencing and differential gene biological function analysis.Results:Compared with blank group,FPG of diabetic GK rats was significantly increased(P<0.01,P<0.05),FINS and HOMA-IR of model group were significantly increased(P<0.01),lipid and liver function indexes were increased in different degrees(P<0.01,P<0.05),and pathological changes were observed in liver.Compared with model group,after 12 weeks treatment,FPG,FINS and HOMA-IR were significantly decreased in Shenqi Compound group(P<0.05,P<0.01),blood lipid(P<0.01,P<0.05),liver function and liver pathological damage were repaired to different degrees.Shenqi Compound had reverse regulation function on 176 circRNAs,and the main difference was that the circRNA host gene clustered in the functional cluster with the endocrine system,lipid metabolism,and other glucose-lipid metabolism signaling pathways as the core.Conclusion:Shenqi Compound may regulate glycolipid metabolism disorder and improve liver pathological damage by widely regulating the differential expression of circRNA and downstream related signaling pathways.

关 键 词：参芪复方 2型糖尿病 GK大鼠 环状RNA 糖脂代谢 

分 类 号：R285.5[医药卫生—中药学]