中药药理与临床2025，Vol.41Issue(9)：9-14,6.
六味地黄提取物调控胰高血糖素样肽-1的"肠促胰素效应"对2型糖尿病大鼠的影响
Effect of Liuwei Dihuang(六味地黄)Extract on Rats with Type 2 Diabetes Mellitus Based on Incretin Effect of GLP-1
摘要
Abstract
Objective:Based on the incretin effect of glucagon-like peptide-1(GLP-1),this paper explored the effect of Liuwei Dihuang(六味地黄)extract(LWDHE)on rats with type 2 diabetes mellitus(T2DM),thereby providing foundation and experimental basis for further devel-opment of LWDHE in the treatment of diabetes,as well as basic theory and methods for studying the molecular mechanism underlying the drug's anti-diabetic effect via GLP-1.Methods:The rat model of T2DM was induced by a high-fat diet and streptozotocin injections.Thirty-six male SD rats were randomly divided into a normal control group,a model control group,a group receiving metformin at 0.23 g/kg,and groups receiving LWDHE at 3.375,6.75,and 13.5 g/kg,with six rats in each group.Each group was given corresponding drugs or distilled water for eight consecutive weeks.Relevant liver and kidney function indicators(ALT,AST,Crea,and BUN),as well as the glycated hemo-globin(HbA1c),GLP-1(7-36),and GLP-1(7-37)levels in rat serum were determined.HE staining was used to detect the pathological changes in rat ileal tissue.RT-PCR was used to detect the mRNA expressions of β-catenin,Tcf7l2,Gsk-3β,and GLP-1-related genes Gcg and Pc3 in rat ileal tissue.Western blot method was used to detect the protein expressions of β-catenin,TCF7L2,p-GSK-3β,GSK-3β,and GLP-1 in rat ileal tissue.Results:ITT experiment results showed that after the intraperitoneal injection of insulin,the blood glucose levels in rats showed a decreasing trend between 30 and 60 min,followed by an increase at 90 min.Compared with those in the normal control group,blood glucose levels in the model control group were increased at all time points(P<0.05).The serum ALT,AST,Crea,BUN,and HbA1c levels were also significantly increased(P<0.05),while the levels of GLP-1(7-36)and GLP-1(7-37)were decreased(P<0.05).The HE stai-ning results showed that the integrity of the ileal structure was damaged,with the intestinal villus loosened,broken,disordered,and uneven in length.A significant thickening of the lamina propria was also observed.The protein expressions of β-catenin,TCF7L2,GLP-1,and p-GSK-3β in rat ileal tissue were downregulated,and the GSK-3β protein expression was upregulated(P<0.05).The mRNA expressions of β-cate-nin,Tcf7l2,Gcg,and Pc3 in rat ileal tissue were downregulated,while the Gsk-3β mRNA expression was upregulated(P<0.05).Compared with those in the model control group,the blood glucose levels in all treatment groups were significantly decreased at all time points(P<0.05).The serum ALT,AST,Crea,BUN,and HbA1c levels were also significantly decreased(P<0.05),while the levels of GLP-1(7-36)and GLP-1(7-37)were increased(P<0.05).The HE staining results show a reduction in pathological damage to the ileal tissue.The pro-tein expressions of β-catenin,TCF7L2,GLP-1,and p-GSK-3β were upregulated in rat ileal tissue(P<0.05),while the protein expression of GSK-3β was downregulated(P<0.05).The mRNA expressions of β-catenin,Tcf7l2,Gcg,and Pc3 were upregulated(P<0.05)in rat ileal tissue(P<0.05),while Gsk-3β mRNA expression was downregulated(P<0.05).Conclusion:LWDHE can effectively improve the liver and kidney functions of T2DM rats,reduce HbA1c,and improve insulin resistance of T2DM rats.Its mechanism may be related to the promotion of the expression and secretion of GLP-1 in ileal tissue,thereby improving the incretin effects,as well as the activation of the Wnt/β-catenin sig-naling pathway.关键词
六味地黄提取物/2型糖尿病大鼠/胰高血糖素样肽-1/β-连环蛋白/糖原合酶激酶-3β/磷酸化糖原合酶激酶-3βKey words
Liuwei Dihuang(六味地黄)extract/Rat with type 2 diabetes mellitus/Glucagon-like peptide(GLP)-1/β-catenin/Glycogen synthase kinase(GSK)-3β/Phospho-GSK-3β引用本文复制引用
周牡娜,肖军,欧阳方丹,郭劲霞,徐群芳,舒盼,王玮,陶虎城..六味地黄提取物调控胰高血糖素样肽-1的"肠促胰素效应"对2型糖尿病大鼠的影响[J].中药药理与临床,2025,41(9):9-14,6.基金项目
湖南省自然科学基金(科药联合)(编号:2022JJ80033) （科药联合）
湖南省自然科学基金(区域联合基金)(编号:2023JJ50363) （区域联合基金）
益阳医学高等专科学校开放性课题(编号:202302). （编号:202302）
