| Objective: In order to explore the effect of modified Xiehuang on glucolipid metabolism in obese insulin resistance rats,this study used high-fat diet to replicate obese insulin resistance rat model.It is expected to provide experimental and theoretical basis for clinical use of traditional Chinese medicine to prevent obesity and related diseases.Methods: In this experiment,60 male SD rats of SPF grade at the age of 5 weeks were purchased.After 1 week of accommodative raising,10 rats were randomly singled out as the common group with normal diet,and the remaining 50 rats were fed with high-fat diet(HFD)as the model group.After 8 weeks of feeding with HFD,we will evaluate whether the model of obese insulin resistance(OIR)rats is successful.After the successful replication of the model,the rats were casually divided into blank group(Control),model group(Model),low-dose group of modified Xiehuangsan(XHS-L),medium-dose group of modified Xiehuangsan(XHS-M),high-dose group of modified Xiehuangsan(XHS-H)and Metformin group(Metformin).Rats in each group were given the homologous liquor by gavage once-daily for 8 weeks.The general condition and death of rats were kept track regularly throughout the experiment.The biochemical indexes of rats in each group were determined,Including fasting blood glucose(FBG),fasting insulin(FINS),triglyceride(TG),total cholesterol(TC),low density lipoprotein-cholesterol(LDL-C),high density lipoprotein-cholesterol(HDL-C),free fatty acid(FFA),alanine trans-ferase(ALT),aspartate transferase(AST)and creatinine(CREA).The spleen index and liver index of rats were calculated.The morphological changes of adipose tissue around epididymis were observed in each group by means of HE coloration and oil red O coloration.Results: 1.Moulding group rats were compared with common group.After 8weeks of HFD,the general situation of rats were as follows: the rats in the common group had pretty fine mental state,acute reaction and normal stool and urine.The rats in the model group were not feeling well physically,slow reaction,excessive urination and loose stool.the food intake of rats in the model group was remarkably lower than that in the common group(P<0.01),and the body weight was significantly higher than that in the common group(P<0.01).The results of OIR rat model were as follows: the levels of FBG and FINS were remarkably incremental(P<0.01)in the model group,and HOMA-IR was also remarkably larger(P<0.01).This indicated that 40 OIR rat models were successfully replicated in this experiment.The changes of rat organ index were as follows: the liver index and spleen index of OIR rats in model group were higher than those in common group(P < 0.05).The morphological changes of periepididymal adipose tissue of rats were as follows: compared with common group,the adipose cells in the model group were blurred in outline,unequal in size,scattered in arrangement,larger in diameter,less in number,and a large number of lipid droplets gathered in the cells.2.Model group rats were compared with Control group.After 8 weeks of gavage,the general situation of OIR rats were as follows: compared with Control group,the rats in Model group had poor mental state,slow reaction,less activity,more urine and loose stool.Food intake and body weight of OIR rats were shown: compared with Control group,food intake and body weight of Model group were remarkably incremental(P<0.01).The liver function and kidney function of OIR rats were as follows: compared with Control group,the concentrations of ALT and AST of rats in Model group were remarkably incremental(P<0.01).Glucose-related indicators of OIR rats were shown:compared with Control group,the concentrations of FBG and FINS of rats in Model group were remarkably incremental(P<0.01),and HOMA-IR were concomitantly increased(P<0.01).Lipid-related indicators of OIR rats were shown: compared with Control group,the concentrations of TG,TC,LDL-C and FFA in serum of Model group were remarkably incremental(P < 0.01),while the serum level of HDL-C was remarkably reduced(P<0.01).The morphological changes of periepididymal adipose tissue were shown: compared with Control group,the adipose cells of periepididymal adipose tissue in Model group were blurred in outline,unequal in size,disorderly in order,enlarged in diameter and decreased in number.3.Rats in drug intervention groups were compared with Model group rats.After 8weeks of gavage,the general situation of OIR rats were as follows: the mental status of rats in each administration group was improved.The response was more sensitive,the urine was normal,the stool was formed.Food intake and body weight of OIR rats were shown: the food intake and body weight of rats in XHS-M group,XHS-H group and Metformin group were reduced(P<0.05).The liver function and kidney function of OIR rats were as follows: the concentration of ALT of rats in XHS-L group was remarkably reduced(P<0.01).The concentrations of ALT and AST of rats in XHS-M group,XHS-H group and Metformin group were remarkably reduced(P<0.01).In addition,there was no statistical deviation in serum concentration of CREA among all groups(P>0.05).Glucose-related indicators of OIR rats were shown: the level of HOMA-IR of rats in XHS-L group was remarkably reduced(P < 0.01).The concentrations of FBG and FINS of rats in XHS-M group,XHS-H group and Metformin group were reduced(P<0.05),and HOMA-IR was all concomitantly decreased(P < 0.01).Lipid-related indicators of OIR rats were shown: serum concentration of TG in XHS-L group was reduced(P<0.05).Serum concentrations of TG,TC,LDL-C and FFA in XHS-M group,XHS-H group and Metformin group were reduced(P<0.05),while serum HDL-C level in XHS-H group was remarkably incremental(P<0.01).The morphological changes of periepididymal adipose tissue were shown: the pathologyical changes of adipose tissue of rats in each administration group improved,with relatively clear outline of adipocytes,relatively uniform cell size,tendency of compact ordering,smaller cell diameter,and increased cell number.4.Rats in Xiehuangsan intervention groups were compared with Metformin group rats.After 8 weeks of gavage,food intake and body weight of OIR rats were shown:the food intake and body weight of rats in XHS-L group were incremental(P<0.05).Glucose-related indicators of OIR rats were shown: the level of FBG of rats in XHS-L group,XHS-M group and XHS-H group was incremental(P<0.01,P<0.01,P<0.05).Lipid-related indicators of OIR rats were shown: serum concentrations of TG and TC in XHS-L group were incremental(P<0.05).The serum concentration of HDL-C in XHS-M group was incremental(P<0.05).Conclusion: 1.Long term intake of a high-fat diet can successfully establish OIR rat models.2.Modified Xiehuangsan can effectively reduce appetite in OIR rats and inhibit body weight gain resulting from a high-fat diet.The glycolipid metabolism of OIR rats was optimized in a dose-dependent manner and the pathological changes of adipose tissue morphology were reversed by modified Xiehuangsan.3.These results suggest that modified Xiehuangsan may play a considerable role in anti-obesity and improving insulin resistance by correcting the disorder of glucose and lipid metabolism in the body. |
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