中国病理生理杂志2025，Vol.41Issue(5)：937-944,8.DOI:10.3969/j.issn.1000-4718.2025.05.012
化浊颗粒调控2型糖尿病大鼠糖原合成及糖异生
Huazhuo granules regulate glycogen synthesis and gluconeogenesis in type 2 diabetic rats
摘要
Abstract
AIM:To observe the effects of Huazhuo granules on phosphatidylinositol 3-kinase(PI3K)/protein kinase B(PKB/Akt)/glycogen synthase kinase-3β(GSK-3β)and PI3K/Akt/forkhead box protein O1(FOXO1)signaling pathways in the liver tissue of type 2 diabetes mellitus(T2DM)rats,and to explore its mechanism of action in regulating glycogen synthesis and gluconeogenesis.METHODS:Thirty 8-week-old SPF-grade male SD rats were chosen,with 5 ran-domly selected ones as the blank control group.The remaining 25 rats were fed to a high-sugar and high-fat diet for 4 weeks,followed by a single intraperitoneal injection of streptozotocin to establish a T2DM rat model.After successful mod-eling,these rats were randomly divided into 5 additional groups:the model group,a positive control group treated with met-formin,and low,medium,and high-dose Huazhuo granule groups,resulting in a total of 6 groups with 5 rats in each.Rats in the treatment groups were gavaged with the corresponding doses of medication,while those in the blank control and model groups were gavaged with an equal volume of saline once daily for 4 consecutive weeks.After 24-hour fasting with free access to water,the rats were euthanized to measure blood glucose,serum insulin levels,and serum triglyceride(TG),total cholesterol(T-CHO),high-density lipoprotein cholesterol(HDL-C),aspartate aminotransferase(AST)and alanine aminotransferase(ALT)levels.Liver pathological morphology was assessed by hematoxylin-eosin staining,and liver glycogen storage was detected by periodic acid-Schiff staining.Immunohistochemistry and Western blot analysis were employed to detect the protein levels of p-PI3K,p-Akt,p-FOXO1 and p-GSK-3β in the liver of rats in each group.The mRNA levels of phosphoenolpyruvate carboxykinase(PEPCK),glucose-6-phosphatase(G6Pase),GSK-3β,FOXO1,PI3K and Akt in liver tissues were detected by RT-qPCR.RESULTS:Compared with the model group,the rats in the high-dose Huazhuo Granule group and the metformin group exhibited decreased blood glucose and insulin levels(P<0.01),reduced AST,ALT,TG,and T-CHO concentrations(P<0.01),and increased HDL-C concentrations(P<0.01).The phosphorylation levels of PI3K,Akt,FOXO1,and GSK-3β proteins were up-regulated(P<0.01).In con-trast,the gene expressions of G6Pase,PERCK,FOXO1,and GSK-3β were all down-regulated(P<0.01).Conversely,the gene expressions of PI3K and Akt were upregulated(P<0.01).Pathological morphology of the liver tissue improved,accompanied by increased glycogen deposition in hepatocytes.CONCLUSION:Huazhuo granule manifests effects in lowering blood glucose and serum insulin levels,ameliorating blood lipids,and enhancing liver function in rats.These ef-fects are revealed to increase glycogen synthesis by activating the PI3K/Akt/GSK-3β signaling pathway and reduce gluco-neogenesis by activating the PI3K/Akt/FOXO1 signaling pathway.关键词
化浊颗粒/2型糖尿病/糖原合成/糖异生/PI3K/Akt/FOXO1信号通路Key words
Huazhuo granules/type 2 diabetes mellitus/glycogen synthesis/gluconeogenesis/PI3K/Akt/FOXO1 signaling pathway分类
医药卫生引用本文复制引用
刘聪聪,张朝宁,陈瑞,脱伟旺,余臣祖..化浊颗粒调控2型糖尿病大鼠糖原合成及糖异生[J].中国病理生理杂志,2025,41(5):937-944,8.基金项目
甘肃中医药大学创新基金重点项目(No.2022KCZD-2) （No.2022KCZD-2）
甘肃省2024年高校教师创新基金项目(No.2024A-092) （No.2024A-092）
