Research On The Effect Of Astragalus-Pueraria Compatibility On Insulin Resistance (STAT3) In High-Fat Rats

Objective:In this study,the effects of the compatibility of Astragalus-Pueraria on the regulation of glucose and lipid metabolism and related proteins of insulin resistance（IR）in high-fat diet（HFD）rats were observed through experimental research,in order to explore the mechanism of action of the compatibility and explore new possible targets and treatment ideas for IR.Materials and methods:The 80 SD rats（male）were fed adaptively for 7days and randomly divided into two groups:blank group（n=10）and high fat group（n=70）.The blank group was fed with conventional diet,and the high-fat group was fed with high-fat diet for 30 days.The high-fat group was given a one-time tail vein injection of streptozotocin（STZ）at a dose of30mg·kg^-1at a concentration of 1%to induce a high-fat IR model,and the fasting blood glucose（FBG）was detected after 72 hours of observation.Dead and unmodeled rats were excluded,the remaining model rats were randomly divided into 5 groups,（1）model group;（2）positive drug group（metformin）;（3）Astragalus-Pueraria high-dose group;（4）Astragalus-Pueraria medium dose group;（5）Astragalus-Pueraria low-dose group,each group of 13.The 10 rats in the blank group were given normal saline by gavage.The positive drug group was given metformin hydrochloride tablet suspension by gavage at a dose of 76.5mg·kg^-1.Each dose group of Astragalus-Pueraria were given respectively by gavage at a dose of 2.03g·kg^-1,4.05g·kg^-1and 8.10g·kg^-1.FBG was recorded every week during the administration period.After 30 days of drug intervention,oral glucose tolerance（OGTT）test was performed,and blood lipid（TC,TG,HDL-C,LDL-C,NEFA）and liver function（ALT,AST）were measured by biochemical analyzer.The contents of adiponectin（ADPN）,interleukin-22（IL-22）and fasting insulin（FINS）in liver tissue were detected by enzyme-linked immunosorbent assay（ELISA）.The expression of signal transduction transcription activator 3（STAT3）and p38 mitogen-activated protein kinase（p38MAPK）in liver tissues were detected by Western blot.The experimental data were analyzed by SPSS 23.0 statistical software.Results:1.Znduced by HFD-STZ,the rats in the model group had obvious manifestations such as polydipsia,polyuria,weight loss,mental fatigue,bradykinesia,and withered hair;Compared with the blank group,FBG,OGTT,IR index and water intake in the model group were significantly increased（P<0.01）;After 30 days of drug intervention,the positive drug group and the high-dose group were significantly lower than the model group（P<0.01）.2.Compared with the blank group,the contents of TC,LDL-C,TG and NEFA in the model group were significantly increased（P<0.01）,and the content of HDL-C in the model group was significantly decreased（P<0.01）;compared with the model group,the contents of TC and LDL-C in the positive drug group and each dose group of Astragalus-Pueraria were significantly decreased（P<0.01）,and the contents of TG and NEFA in the positive drug group and the high and medium dose groups were significantly decreased（P<0.01）,the content of HDL-C in the positive drug group and the high-dose group was significantly increased（P<0.01）.3.Compared with the blank group,the contents of ALT,AST and glycogen in the model group were significantly increased（P<0.01）,and the glycogen content in the model group was significantly decreased（P<0.01）.Compared with the model group,the contents of AST and ALT in the positive drug group and each dose group of Astragalus-Pueraria were significantly decreased（P<0.01）,and the content of liver glycogen in the positive drug group,high and medium dose groups were significantly increased（P<0.01）.4.In terms of liver tissue related protein expression,compared with blank group,the expression of p38MAPK and STAT3 in model group were significantly increased（P<0.01）,the contents of ADPN and IL-22 were significantly decreased（P<0.01）.Compared with the model group,The expressions of p38MAPK and STAT3 in the positive drug group and each dose group of Astragalus-Pueraria were significantly down-regulated（P<0.01）,while the contents of ADPN and IL-22 in the liver tissue of the positive drug group and the high-dose group were significantly increased（P<0.01）.Conclusion:1.The compatibility of Astragalus and Pueraria can regulate the glucose and lipid of IR in high-fat rats,repair the chronic lipotoxic injury of the liver,improve the synthesis function of liver glycogen and the problem of liver IR.2.The compatibility of Astragalus and Pueraria regulates the related proteins of IR in high-fat rats,which may be related to the up-regulation of ADPN and IL-22 contents,and the inhibition of p38MAPK and STAT3signaling pathway.