文献类型：期刊文献

中文题名：化浊颗粒调控2型糖尿病大鼠糖原合成及糖异生

英文题名：Huazhuo granules regulate glycogen synthesis and gluconeogenesis in type 2 diabetic rats

作者：刘聪聪[1];张朝宁[1];陈瑞[1];脱伟旺[1];余臣祖[1]

第一作者：刘聪聪

机构：[1]甘肃中医药大学,甘肃兰州730000

第一机构：甘肃中医药大学

年份：2025

卷号：41

期号：5

起止页码：937

中文期刊名：中国病理生理杂志

外文期刊名：Chinese Journal of Pathophysiology

收录：;北大核心:【北大核心2023】；

基金：甘肃中医药大学创新基金重点项目(No.2022KCZD-2);甘肃省2024年高校教师创新基金项目(No.2024A-092)。

语种：中文

中文关键词：化浊颗粒;2型糖尿病;糖原合成;糖异生;PI3K/Akt/FOXO1信号通路

外文关键词：Huazhuo granules;type 2 diabetes mellitus;glycogen synthesis;gluconeogenesis;PI3K/Akt/FOXO1 signaling pathway

摘要：目的:观察化浊颗粒对2型糖尿病(type 2 diabetes mellitus,T2DM)大鼠肝组织磷酯酰肌醇3-激酶(phosphatidylinositol 3-kinase,PI3K)/蛋白激酶B(protein kinase B,PKB/Akt)/糖原合成酶激酶3β(glycogen synthase kinase-3β,GSK-3β)和PI3K/Akt/叉头框蛋白O1(forkhead box protein O1,FOXO1)信号通路的影响,探讨其调控糖原合成及糖异生的作用机制。方法:8周龄SPF级雄性SD大鼠30只,随机取5只为空白对照组,其余25只经过高糖高脂饮食4周后,一次性腹腔注射链脲佐菌素建立T2DM大鼠模型,成模后随机分为模型组、阳性对照药物二甲双胍组及低、中、高剂量化浊颗粒组,每组5只。各给药组大鼠灌胃相应剂量的药物,空白对照组和模型组大鼠灌胃等体积生理盐水,每日1次,连续灌胃4周。禁食不禁水24 h后处死,测血糖及血清胰岛素、甘油三酯(triglyceride,TG)、总胆固醇(total cholesterol,T-CHO)、高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDL-C)、天冬氨酸氨基转移酶(aspartate aminotransferase,AST)和丙氨酸氨基转移酶(alanine aminotransferase,ALT)水平;采用苏木素-伊红染色检测肝脏病理形态;过碘酸-希夫染色检测肝糖原存储;免疫组化及Western blot法检测各组大鼠肝脏p-PI3K、p-Akt、p-FOXO1和p-GSK-3β蛋白水平;采用RT-qPCR检测肝组织磷酸烯醇式丙酮酸羧激酶(phosphoenolpyruvate carboxykinase,PERCK)、葡萄糖-6-磷酸酶(glucose-6-phosphatase,G6Pase)、GSK-3β、FOXO1、PI3K和Akt mRNA水平。结果:与模型组相比,高剂量化浊颗粒组和二甲双胍组大鼠血糖和胰岛素水平下降(P<0.01),AST、ALT、TG和T-CHO水平降低(P<0.01),HDL-C含量升高(P<0.01)。PI3K、Akt、FOXO1和GSK-3β蛋白磷酸化水平上调(P<0.01),G6Pase、PERCK、FOXO1和GSK-3β的mRNA表达水平均降低(P<0.01),PI3K和Akt的mRNA表达水平升高(P<0.01)。肝组织病理形态改善;肝细胞糖原沉积增加。结论:化浊颗粒可降低T2DM大鼠血糖、血脂及血清胰岛素水平,改善大鼠肝功能,增加肝糖原储备。该作用与其通过激活PI3K/Akt/GSK-3β通路增加糖原合成和激活PI3K/Akt/FOXO1通路减少糖异生有关。
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 randomly 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 modeling,these rats were randomly divided into 5 additional groups:the model group,a positive control group treated with metformin,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-3βin 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-3βproteins were up-regulated(P<0.01).In contrast,the gene expressions of G6Pase,PERCK,FOXO1,and GSK-3βwere 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 effects are revealed to increase glycogen synthesis by activating the PI3K/Akt/GSK-3βsignaling pathway and reduce gluconeogenesis by activating the PI3K/Akt/FOXO1 signaling pathway.