| Objective:Taking SD rats as the research object,the obese rat model was established,and total flavonoids of Melastoma dodecandrum Lour.(TFMD)were given by gavage at the same time to study the intervention effect and mechanism of preventing obesity,so as to provide experimental basis for the development of weight loss and lipid-lowering products with TFMD.Methods: 85 SPF grade male rats were randomly divided into blank group and induction group.Rats in blank group were given normal diet,while rats in induction group were given high-fat diet.After feeding for 2 weeks,the rats in the induction group with light weight were eliminated,and the remaining rats were randomly divided into model group(high-fat diet),orlistat group(high-fat diet+60mg/kg orlistat),TFMD high-dose group(high-fat diet+750mg/kg TFMD),medium-dose group(high-fat diet+500mg/kg TFMD)and low-dose group(high-fat diet+330mg/kg TFMD),10 rats in each group.During the administration,recording the general condition,body weight and Lee’s index of rats in each group.After 6 weeks,fasting blood glucose(FBG)and oral glucose tolerance(OGTT)were measured by tail cutting;blood samples from abdominal aorta were dissected to detect serum total cholesterol(TC),triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),alanine aminotransferase(ALT),aspartate aminotransferase(AST)and blood urea nitrogen(BUN)Insulin(INS),adiponectin(ADP)and leptin(LEP)were detected by ELISA;Calculated each organ index and fat coefficient;Detected the contents of TG and TC in livers;Made red O staining of livers and HE stained sections of fat in each group of rat.The expressions of Adipo R2,p38 and PPARγ were examined using Western Blot method.The real-time fluorescence quantitative PCR were used to evaluate the Adipo R2,p38 and PPARγ gene expression.The sequencing technology 16 S rRNA was used to explore the TFDM on the structure of intestinal microflora in the process of obesity.Results: After monitoring the general situation of rats in each group,it was found that there was no significant difference in the initial body weight of rats in each group(P>0.05).At the end of 6 weeks,the body weight,Lee’s index and fat coefficient of the model group were significantly higher than those of the blank group(P<0.01),indicating that the obese rat model was successfully established.Compared with the model group,the body weight and fat coefficient of orlistat group and each dose group of TFMD were significantly decreased(P<0.01),and the Lee’s index of orlistat group and high-dose group of TFMD was extremely significant(P<0.01).Compared with the blank group,the liver coefficient and kidney coefficient of the model group were increased(P<0.01);compared with the model group,there was no significant difference in the mass coefficient of each organ in each group(P>0.05).In the serum biochemical test,compared with the blank group,the content of TC and TG in the model group was significantly increased(P<0.01),and the content of HDL-C was significantly decreased(P<0.01);compared with the model group,the content of TC in the orlistat group was significantly decreased(P<0.05),and the content of HDL-C was significantly increased(P<0.05);the content of TC and TG in the high-dose group of TFMD was significantly decreased(P>0.05),The content of HDL-C was significantly increased(P<0.01).The content of TG in the medium-dose group of TFMD was significantly decreased(P<0.05)and the HDL-C was significantly increased(P<0.05).Compared with the blank group,the content of Cr in the serum of the model group was significantly increased(P<0.01),the content of ALT and AST was significantly increased(P<0.05);compared with the model group,the content of AST in the serum of the orlistat group was significantly decreased(P<0.01),the content of Cr was significantly decreased(P<0.05),the content of ALT and AST in the serum of the high-dose group of TFMD were significantly decreased(P<0.01),and the content of Cr was significantly decreased(P<0.05),The levels of AST and Cr in the mediumdose group of TFMD were significantly decreased(P<0.05),The levels of ALT in the low-dose group of TFMD was significantly decreased(P<0.01).Liver tissue homogenate showed that TC and TG in the model group were significantly higher than blank group(P<0.01);TC and TG in the liver of each drug group were significantly lower than model group(P<0.05 or P<0.01).In oral glucose tolerance experiment,compared with the blank group,the blood glucose values of rats in the model group was increased(P<0.01).Compared with the model group,the blood glucose of each treatment groups were decreased at 0-2 h(P<0.05 or P<0.01),and the AUC of each treatment group was decreased(P<0.01).ELISA experiment showed that the levels of INS,ADP and LEP in the model group were higher than blank group(P<0.05 or P<0.01),and the levels of INS,ADP and LEP in the serum of each treatment group were lower than model group(P<0.05 or P<0.01).The results of pathological observation showed that compared with the model group,the degree of lipid deposition in the liver of each treatment group was slowed down,which could effectively prevent fatty liver induced by high-fat diet,and inhibition of adipocyte enlargement.The results of western blot showed that compared with the model group,the expression of Adipo R2,p38 and PPARγ protein in liver tissue of rats in each treatment group was increased(P<0.01).The results of the real-time fluorescence quantitative PCR showed that compared with the model group,the mRNA levels of Adipo R2,p38 and PPARγ were significantly increased in each treatment group(P<0.01).After 6 weeks,the feces of rats in blank group,model group and high-dose group of TFMD were detected by 16 S rRNA high-throughput sequencing technology.The results showed that compared with the blank group,the diversity of intestinal microflora in the model group decreased,and the diversity of intestinal microflora in each treatment group increased compared with the model group,which indicated that TDMF could effectively reverse the intestinal microflora disorder caused by long-term high-fat diet.Conclusion: TFMD had a good effect on preventing obesity and reducing blood lipid,the mechanism of weight loss and lipid reduction mould be related to improve glucose and lipid metabolism,increasing the protein and gene expression of Adipo R2,p38 and PPARγ in liver,increasing the diversity of intestinal flora and regulating structure of intestinal flora. |