Effect of Andrographolide on Insulin Resistance Rats and Analysis of Its Possible Mechanisms of Action
Objective To investigate the effect and possible mechanism of andrographolide on insulin resistance in rats.Method A total of 48 healthy adult Wistar rats with SPF grade were obtained,and 36 rats were randomly fed with high-fat and high-sugar diets to establish an experimental Wistar rat insulin resistance(IR)model.The rats were divided into blank control model group(HFD group),androlianolide high-dose group(High group)and androlianolide low-dose group(Low group)according to random number allocation method.Twelve rats were selected to receive normal diet as the normal control group(NC group),High group was given intraperitoneal injection of andrographolide 200 mg/(kg·d).Low group was given intraperitoneal injection of andrographolide 100 mg/(kg·d).HFD group and NC group were only given intraperitoneal injection of the same amount of nor-mal saline for 14 consecutive days.Fasting blood glucose(FBG)was monitored by glucose oxidase method,and fasting insulin(FINS)was detected by ELISA method.The homeostasis model assessment-insulin resistance(HOM A-IR)was calculated.The pathological changes of liver were detected by red O staining.The activity of superoxide dismutase(SOD)was measured by biphloroglucinol autoxidation method,and malondialdehyde(MDA)level was measured by thiobarbituric acid method.Immuno-histochemical detection of ribosomal protein S6 kinase in rat liver tissue(ribosomal protein S6 kinase,S6K1)and p-insulin re-ceptor substrate-1(p-IRS-1)(Tyr632)protein expression levels.Western blotting was used to detect expression levels of S6K1 and p-IRS-1(Tyr632)in liver tissues.The SPSS 23.0 software package was used for analysis.Result Compared with those of the NC group,the levels of FBG,FINS and HOMA-IR in the HFD group,High group and Low group were significantly increased(P＜0.05).Compared with the HFD group,the other three groups had lower levels of FBG,FINS and HOMA-IR(P＜0.05).Compared with the Low group,the High group had lower levels of FBG,FINS and HOMA-IR(P＜0.05).Com-pared with that of the NC group,the average optical density of the HFD group increased(P＜0.05).Compared with the HFD group,the High and Low groups showed a decrease in lipid droplet area/total muscle fiber area,and average optical density(P＜0.05).Compared with the Low group,the High group had lower average lipid droplet area/total muscle fiber area and optical density(P＜0.05).Compared with those of the NC group,the SOD activity and MDA content in the HFD group increased(P＜0.05).Compared with those of the HFD group,the SOD activity and MDA content in the High and Low groups decreased(P＜0.05).Compared with the Low group,the High group had lower SOD activity and MDA content(P＜0.05).Compared with those of the NC group,the relative expression of FAT/CD36 protein in the HFD group increased,while the relative expression of CPT-1 protein decreased(P＜0.05).Compared with those of the HFD group,the relative expression of FAT/CD36 protein in the High and Low groups decreased,while the relative expression of CPT-1 protein increased(P＜0.05).Compared with the Low group,the High group had lower relative expression levels of FAT/CD36 protein and higher relative expression levels of CPT-1 protein(P＜0.05).Compared with those of the NC group,the relative expression of FAT/CD36mRNA in the HFD group increased,while the relative expression of CPT-1 mRNA decreased(P＜0.05).Compared with those of the HFD group,the rela-tive expression of FAT/CD36mRNA in the High and Low groups decreased,while the relative expression of CPT-1mRNA in-creased(P＜0.05).Compared with the Low group,the High group had lower relative expression levels of FAT/CD36 mRNA and higher relative expression levels of CPT-1 mRNA(P＜0.05).Conclusion Andrographolide can improve the insulin resistance status and significantly improve the IR status of IR rats.Its therapeutic mechanism is closely related to improving oxidative stress status,down-regulating the expression of S6K1 and increasing the tyrosine phosphorylation level of IRS-1.
万方数据
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