| Objective:(1)The purpose of this study was to establish a rat model of insulin resistance(IR)to determine the protein expression of adiponectin-1(Lipin-1)and adiponectin-2(Lipin-2)in the liver under the condition of insulin resistance,and to explore the role of liver Lipin-1 and Lipin-2 in insulin resistance.(2)To observe the intervention effect of Huazhuo Jiedu Decoction on insulin resistance.(3)To explore the effect of Huazhuo Jiedu Decoction on Lipin-1 and Lipin-2 in the liver of insulin resistant rats and its possible mechanism,so as to provide new ideas and methods for the treatment of T2DM(Type 2 diabetes mellitus)in traditional Chinese medicine.Methods:(1)In this study,70 healthy male rats were selected and the breed was SD.Ten of them were named as blank control group,and the remaining 60 were named as IR model group.The construction method of insulin resistance model: after being treated with high-fat diet for 8 weeks,the insulin resistance model was constructed with streptozotocin.The rats who completed the construction of the model were named as model group,low-dose Huazhuo Jiedu Decoction group,middle-dose Huazhuo Jiedu Decoction group and high-dose Huazhuo Jiedu Decoction group.The rats in the three dose groups intervened by Huazhuo Jiedu Decoction were given intragastric administration of 1.5g,3.0g and 6.0g / kg·d,respectively.The rats in the blank control group and model group were treated with the same amount of normal saline for 4 weeks,and the rats in each group were killed after intragastric administration.(2)During the experiment,the changes of body weight and fasting blood glucose(FBG)were regularly monitored,and glucose tolerance test was performed.Triglyceride(TC)and total cholesterol(TG),were measured after intragastric administration of(OGTT);Serum FINS(fasting insulin)was detected by radioimmunoassay,and insulin sensitivity index(HOMA-ISI)and insulin resistance index(HOMA-IR)were calculated by formula.The expression levels of Lipin-1 and Lipin-2 in liver tissue of rats in each group were detected by Western blotting(Western blot),and the morphology of liver tissue was observed by hematoxylin-eosin staining(Hematoxylin-eosin staining,HE).Statistical analysis was carried out with SPSS 26.0.the experimental data were expressed by mean ±standard deviation(x ±s).The comparison between groups was made by single factor analysis of variance(One-Way ANOVA),pairwise comparison,t-test,P < 0.05.the difference was statistically significant.Results:(1)FBG,TC,TG,FINS and HOMA-IR increased and OGTT,HOMA-ISI decreased in insulin resistant rats,compared with the blank control group,the difference was statistically significant(P < 0.01).(2)In insulin resistant rats,the structure of liver tissue was disordered,hepatocytes were obviously swollen,and scattered lipid droplet vacuoles and inflammatory cell infiltration were observed in the cytoplasm.(3)The expression of Lipin-1 in the liver of insulin resistant rats decreased and the expression of Lipin-2 increased,which was significantly higher than that in the blank control group(P < 0.01).(4)The levels of FBG,TC,TG,FINS and HOMA-IR decreased,OGTT was decreased,HOMA-ISI increased in the low,middle and high dose groups of Huazhuo Jiedu Decoction,which were different from those in insulin resistance model group.(5)The liver lipid droplet vacuoles and inflammatory cell infiltration in the low,middle and high dose groups of Huazhuo Jiedu Decoction were reduced and relieved in varying degrees.(6)The expression of Lipin-1 in low,middle and high dose groups of Huazhuo Jiedu Decoction increased and the expression of Lipin-2 decreased,which was different from that in insulin resistance model group.Conclusion:(1)Under the condition of insulin resistance,FBG,TC,TG,FINS and HOMA-IR increased,OGTT,HOMA-ISI decreased,Lipin-1 protein expression decreased,Lipin-2 protein expression increased,which caused liver tissue structure disorder,lipid deposition and inflammation.It is suggested that the disorder of glucose and lipid metabolism in insulin resistance may be related to the expression of Lipin-1 and Lipin-2.(2)Huazhuo jiedu decoction decreased FBG,TC,TG,FINS and HOMA-IR under IR condition,increased HOMA-ISI,improved OGTT,up-regulated the expression level of LIPIN-1 protein,decreased the expression level of LIPIN-2 protein,alleviated the structural disorder,lipid deposition and inflammatory response of liver tissue,improved liver injury and protected liver.Huazhuo Jiedu Prescription is effective in regulating glucose and lipid metabolism disorders in the liver under the condition of insulin resistance,and its mechanism of action may be related to regulating the expression of Lipin-1 and Lipin-2 in the liver,which provides a scientific experimental basis and a new idea for the diagnosis and treatment of insulin resistant type 2 diabetes. |
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