摘要
目的:研究七味白术散对高脂饮食与链脲佐菌素(STZ)导致的糖尿病小鼠肝脏组织中磷脂酰肌醇-3激酶(PI3K)/蛋白激酶B(Akt)信号通路的影响。方法:采用网络药理与实验药理学的方法研究七味白术散的降糖作用。通过公共数据库筛选活性成分和疾病靶点,构建成分-靶点和疾病-靶点的PPI网络,进行基因本体(GO),京都基因和基因组百科全书(KEGG)富集分析信号通路。以高糖高脂饲料联合腹腔注射80 mg·kg^-1·d^-1STZ建立糖尿病小鼠模型,分为正常组(生理盐水)、模型组(生理盐水)、七味白术散祖(七味白术散煎剂18.7 g·kg^-1·d^-1),灌胃28 d后分析其降糖作用及对血清总胆固醇(T-CHO),空腹胰岛素(FINS)含量和血清肿瘤坏死因子-α(TNF-α)的影响,采用实时荧光定量聚合酶链式反应(Real-time PCR),蛋白免疫印迹法(Western blot)检测肝脏组织的胰岛素受体(IR),胰岛素受体底物^-1(IRS^-1),PI3K和Akt蛋白和mRNA的表达。结果:网络药理学研究共筛选到36种活性成分,KEGG分析推测七味白术散可能是通过调节PI3K/Akt信号通路发挥降糖作用的。实验药理学实验表明,七味白术散组与模型小鼠相比,血糖含量、血清TNF-α和T-CHO显著降低(P<0.01),FINS显著升高(P<0.01)。肝脏组织的IR,IRS^-1,PI3K和Akt蛋白和mRNA的表达明显升高(P<0.05,P<0.01)。结论:七味白术散可下调高脂饮食和STZ导致FINS升高,其调节作用与PI3K/Akt信号通路与胰岛素的代谢效应有关。
Objective: To study the effect of Qiwei Baizhusan(QWBZS) on liver insulin phosphatidylinositol 3-kinase(PI3 K)/protein kinase B(Akt)signal pathway of diabetic mice induced by high-fat diet and streptozotocin(STZ). Method: The methods of network pharmacology and animal experiments were used to study the hypoglycemic effect of QWBZS. Active chemical components of the drug and disease targets selected through public databases were used to construct the protein-protein interaction network(PPIN),and gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomics(KEGG)enrichment analysis was performed to identify relevant signal pathways in vivo. In the pharmacological experiment,the diabetic mice model was established through intraperitoneal injection with 80 mg·kg^-1·d^-1 STZ high-glucose,high-fat diet. The mice were divided into normal group(normal saline),model group(normal saline)and QWBZS group(18.7 g·kg^-1·d^-1). After 28 days,the hypoglycemic effect of the drug and its effect on serum total cholesterol(TCHO),fasting insulin(FINS)and serum tumor necrosis factor-α(TNF-α)were determined. Western blot and Real-time fluorescence quantitative PCR(Real-time PCR)were used to detect protein and mRNA expressions of insulin receptor(IR),insulin receptor substrate^-1(IRS^-1),phosphatidylinositol 3-kinase(PI3 K)and protein kinase B(Akt)in liver tissues. Result:A total of 36 active components in this drug were identified by network pharmacology. KEGG analysis suggested that QWBZS might play a role in reducing blood glucose by regulating PI3 K Akt signal pathway. Compared with the model group,the levels of blood glucose,serum T-Cho and TNF-αof the intervention group were significantly lower(P<0.01),while the FINS of the intervention group was significantly higher(P<0.01). Protein and mRNA expressions of IR,IRS^-1,PI3 K and Akt in liver tissues of mice in QWBZS treatment group increased markedly(P<0.05,P<0.01). Conclusion: QWBZS could regulate the levels of blood glucose,TNF-α,T-CHO,and FINS in the serum of diabetic mice
作者
刘仕琦
李冀
王艳
LIU Shi-qi;LI Ji;WANG Yan(Heilongjiang University of Chinese Medicine,Harbin 150040,China;Shanxi University of Chinese Medicine,Jinzhong 030619,China)
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2020年第20期153-160,共8页
Chinese Journal of Experimental Traditional Medical Formulae
基金
2014全国名老中医药专家传承工作室建设项目(2014)。
