文献类型：期刊文献

中文题名：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

英文题名：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

作者：崔泽方[1];李钦[2];梁永林[1];朱向东[3];肖露露[1];张玉香[4];寇宁[4]

第一作者：崔泽方

机构：[1]甘肃中医药大学,兰州730000;[2]湖南医药学院,怀化418000;[3]宁夏医科大学中医学院,银川750000;[4]甘肃卫生职业学院,兰州730000

第一机构：甘肃中医药大学

年份：2025

卷号：41

期号：1

起止页码：39

中文期刊名：中药药理与临床

外文期刊名：Pharmacology and Clinics of Chinese Materia Medica

收录：;北大核心:【北大核心2023】；

基金：高校教师创新基金项目(编号:2023A-298);甘肃省中医药科研立项课题(编号:GZKP-2022-41);宁夏回族自治区重点研发重点项目(编号:2022BEG02034)。

语种：中文

中文关键词：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4

外文关键词：Shenqi Tangluo Formula(参七糖络方);Diabetes;Forkhead box protein O1;Long non-coding RNA MEG3,G6Pase,ATF4

摘要：目的:基于长链非编码RNA MEG3(LncRNA MEG3)/微小RNA 214(miR-214)/叉头框蛋白O1(FoxO1)通路探讨参七糖络方对2型糖尿病大鼠肝脏糖异生的影响。方法:80只SD大鼠随机选取12只大鼠作为正常对照组,给予普通饲料喂养,剩余大鼠通过高糖高脂饲料喂养联合腹腔注射小剂量链脲佐菌素(STZ)方法建立2型糖尿病大鼠模型。造模成功后,随机分为模型对照组、参七糖络方13.4、26.8、53.6 g/kg组以及盐酸二甲双胍0.18 g/kg组,12只/组。给药组灌胃给予相应药物治疗,正常对照组及模型对照组灌胃给予等体积生理盐水,1次/d,给药28 d。给药期间检测大鼠空腹血糖,进行丙酮酸耐量试验评估糖异生程度,给药结束后采用苏木素-伊红(HE)染色观察大鼠肝组织的病理形态变化;采用ELISA法检测大鼠肝糖原、谷草转氨酶(AST)、谷丙转氨酶(ALT)含量;采用RT-qPCR法检测肝组织MEG3、miR-214、活化转录因子4(Atf4)、葡萄糖-6-磷酸酶(G6Pase)、磷酸烯醇式丙酮酸羧激酶(Pepck)mRNA表达;采用Western blot法检测肝组织ATF4、FoxO1、胞核蛋白、p-FoxO1蛋白表达。结果:与正常对照组相比,模型对照组大鼠空腹血糖升高,肝组织病理损伤较重,肝组织Pepck、G6Pase、Meg3 mRNA,ATF4蛋白及mRNA、FoxO1的蛋白表达明显上调(P<0.05或P<0.01),miR-214的表达显著下调(P<0.01),FoxO1核转位增加,糖异生增加,肝糖原储存减少;与模型对照组比较,盐酸二甲双胍0.18 g/kg、参七糖络方13.4、26.8、53.6 g/kg组大鼠空腹血糖显著降低(P<0.01),肝组织病理损伤减轻,肝组织Meg3 mRNA、ATF4蛋白及mRNA、FoxO1的蛋白表达明显下调(P<0.05或P<0.01),miR-214的表达显著上调(P<0.01),FoxO1核转位被抑制,糖异生减少,肝糖原储存增加。结论:参七糖络方可以有效抑制糖尿病大鼠肝糖异生,其机制可能与MEG3调控FoxO1有关。
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.Fasting 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 protein,total FoxO1 protein,and nuclear protein p-FoxO1.Results:Compared with the results in the normal control group,the fasting blood glucose 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 decreased.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.