中药药理与临床2025，Vol.41Issue(1)：39-44,6.
参七糖络方调控LncRNA MEG3/miR-214/FoxO1信号通路抑制2型糖尿病大鼠肝脏糖异生
Effect of Shenqi Tangluo Formula(参七糖络方)on Hepatic Gluconeogenesis in Type 2 Diabetic Rats Based on LncRNA MEG3/miR-214/FoxO1 Signaling Pathway
摘要
Abstract
Objective:To investigate the effect of Shenqi Tangluo Formula(参七糖络方)on hepatic gluconeogenesis in type 2 diabetic rats based on the long non-coding RNA MEG3(LncRNA MEG3)/microRNA 214(miR-214)/forkhead box protein O1(FoxO1)pathway.Methods:Twelve rats were randomly selected from 80 SD rats,assigned to the normal control group,and fed on a normal diet.The remaining rats were given a high-sugar and high-fat diet combined with a low-dose streptozotocin(STZ)by intraperitoneal injection to establish a type 2 diabetic rat model.After successful modeling,the rats were randomly divided into the model group,Shenqi Tangluo Formula 13.4,26.8,and 53.6 g/kg groups,and a metformin group(0.18 g/kg),with 12 rats in each group.The treatment groups were given the corresponding drugs,and the normal control group and the model group were given the same volume of normal saline by gavage once a day for 28 days.Fast-ing blood glucose of rats in each group was detected during administration,and a pyruvate tolerance test was performed to evaluate the degree of gluconeogenesis.After administration,hematoxylin-eosin(HE)staining was used to observe the pathological changes in liver tissue in rats.The levels of liver glycogen,AST,and ALT were detected by ELISA.The mRNA expression levels of MEG3,miR-214,ATF4,G6Pase,and PEPCK were detected by real-time fluorescence quantitative PCR(RT-qPCR).Western blotting was used to detect the content of ATF4 pro-tein,total FoxO1 protein,and nuclear protein p-FoxO1.Results:Compared with the results in the normal control group,the fasting blood glu-cose of the model control group was increased(P<0.01),the pathological damage of liver tissue was severe,and the expression levels of MEG3,ATF4,and FoxO1 were significantly up-regulated(P<0.05 or P<0.01).Moreover,the expression of miR-214 was significantly down-regulated(P<0.01).The nuclear translocation of FoxO1 was increased,gluconeogenesis was increased,and liver glycogen storage was de-creased.Compared with the results in the model group,the fasting blood glucose of rats in the 0.18 g/kg metformin hydrochloride group and Shenqi Tangluo Formula groups at doses of 13.4,26.8,and 53.6 g/kg was reduced(P<0.01).The pathological damage of liver tissue was alleviated,the expression levels of lncMEG3,ATF4,and FoxO1 were significantly down-regulated(P<0.05 or P<0.01),and the expression of miR-214 was up-regulated(P<0.01).The nuclear translocation of FoxO1 was inhibited,gluconeogenesis was reduced,and liver glycogen storage was increased.Conclusion:Shenqi Tangluo Formula can effectively inhibit hepatic gluconeogenesis in diabetic rats,and its mechanism may be related to the regulation of FoxO1 by MEG3.关键词
参七糖络方/糖尿病/叉头框蛋白O1/长链非编码RNA MEG3/葡萄糖-6-磷酸酶/活化转录因子4Key words
Shenqi Tangluo Formula(参七糖络方)/Diabetes/Forkhead box protein O1/Long non-coding RNA MEG3,G6Pase,ATF4引用本文复制引用
崔泽方,李钦,梁永林,朱向东,肖露露,张玉香,寇宁..参七糖络方调控LncRNA MEG3/miR-214/FoxO1信号通路抑制2型糖尿病大鼠肝脏糖异生[J].中药药理与临床,2025,41(1):39-44,6.基金项目
高校教师创新基金项目(编号:2023A-298) （编号:2023A-298）
甘肃省中医药科研立项课题(编号:GZKP-2022-41) （编号:GZKP-2022-41）
宁夏回族自治区重点研发重点项目(编号:2022BEG02034). （编号:2022BEG02034）
