中国现代中药2025,Vol.27Issue(10):1906-1916,11.DOI:10.13313/j.issn.1673-4890.20250415004
青钱柳-杜仲叶对db/db小鼠糖脂代谢及肝脏PI3K/Akt/GSK3β信号通路的影响
Effects of Cyclocaryae Paliuri Folium-Eucommiae Folium on Glucose and Lipid Metabolism and PI3K/Akt/GSK3β Signaling Pathway in the Liver in db/db Mice
摘要
Abstract
Objective:To investigate the effects of the herb pair Cyclocaryae Paliuri Folium-Eucommiae Folium on glucose and lipid metabolism and the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/glycogen synthase kinase 3β(GSK3β)signaling pathway in the liver of db/db mice.Methods:Fasting blood glucose was measured at the same time for two consecutive days.According to body weight,30 db/db mice were allocated into model,metformin,low-,medium-,and high-dose herb pair groups by the method of random stratified sampling.The normal group consisted of m/m mice of the same age,with 6 mice in each group.Mice in the low-,medium-,and high-dose herb pair groups were administrated with an alcohol extract of Cyclocaryae Paliuri Folium-Eucommiae Folium.In the low-,medium-,and high-dose herb pair groups,the doses of Cyclocaryae Paliuri Folium were 78.0,156.0,and 312.0 mg·kg-1·d-1,and those of Eucommiae Folium were 175.5,351.0,and 702.0 mg·kg-1·d-1,respectively.Mice in the normal group and model group received the same volume of deionized water.The gavage lasted for 6 weeks.Fasting blood glucose and body mass were measured every week.In the last week,an oral glucose tolerance test was carried out.The levels of triacylglycerol(TG),total cholesterol(TC),and fasting insulin(FINS)in the serum of mice from each group were measured using the enzyme-linked immunosorbent assay(ELISA),and the insulin resistance index was calculated.The pathological conditions,lipid deposition,and glycogen distribution in the liver were observed by hematoxylin-eosin staining,oil red O staining,and periodic acid-Schiff(PAS)staining.Real-time PCR was employed to measure the mRNA levels of PI3K,Akt,and GSK3β,and Western blot was employed to determine the expression levels of Pl3K,Akt,and GSK3β and their phosphorylated proteins in the liver tissue.Results:Compared with the normal group,the model group mice exhibited significantly increased body weight,fasting blood glucose levels,oral glucose tolerance test parameters,area under the curve,fasting insulin levels,insulin resistance index,and triglycerides(P<0.05,P<0.01).Histologically,the model group mice demonstrated severe hepatic steatosis and lipid deposition,along with markedly reduced glycogen synthesis.GSK3β mRNA expression levels markedly increased(P<0.01),while PI3K and Akt mRNA expression levels significantly decreased(P<0.01).The relative protein expression ratios of p-PI3K/PI3K,p-Akt/Akt,and p-GSK3β/GSK3β also significantly declined(P<0.01).Compared with the model group,mice in the Qingqianliu-Eucommia leaf group exhibited significantly reduced body weight,fasting blood glucose levels,oral glucose tolerance test parameters,area under the curve,fasting insulin levels,insulin resistance index,and triglycerides(P<0.05,P<0.01);partial reduction in hepatic morphological alterations,decreased lipid droplets,and increased glycogen distribution;GSK3β mRNA expression levels were markedly decreased,while PI3K and Akt mRNA expression levels were significantly increased.The relative expression levels of p-PI3K/PI3K,p-Akt/Akt,and p-GSK3β/GSK3β proteins were significantly elevated(P<0.05,P<0.01).Conclusion:Cyclocaryae Paliuri Folium-Eucommiae Folium can reduce the fasting blood glucose,early body mass,insulin resistance,and blood lipid levels in db/db mice by activating the PI3K/Akt/GSK3β pathway to promote glycogen synthesis and reduce blood glucose.关键词
2型糖尿病/青钱柳-杜仲叶/磷脂酰肌醇3-激酶/蛋白激酶B/糖原合成酶激酶3β信号通路Key words
type 2 diabetes mellitus/Cyclocaryae Paliuri Folium-Eucommiae Folium/phosphatidylinositol 3-kinase/protein kinase B/glycogen synthase kinase 3β signaling pathway分类
中医学引用本文复制引用
孙亚惠,刘玮,朱怡霏,陈源,王茜,吴丽丽,秦灵灵,刘铜华..青钱柳-杜仲叶对db/db小鼠糖脂代谢及肝脏PI3K/Akt/GSK3β信号通路的影响[J].中国现代中药,2025,27(10):1906-1916,11.基金项目
2020年度新建高等学校学科创新引智基地项目(B20055) (B20055)