| Objective:Leptin resistance plays an important role in the occurrence and development of type 2 diabetes mellitus.in this study,the obese rat model of leptin resistance was established by high fat diet.The effects of acupoint electrical stimulation,swimming exercise and drug intervention on the related indexes of blood glucose and blood lipids and the levels of PTP-1B and SOCS-3 in hypothalamus of obese rats were compared,and the possible mechanism of leptin resistance and insulin sensitivity was discussed.In order to provide experimental basis for clinical intervention of obesity and related diseases caused by leptin resistance.Methods:Fifty 8-week-old SPF male wistar rats were randomly divided into normal control group(n=10)and high-fat group(n=40).The rats were fed with normal diet and high-fat diet for 8 weeks.The body weight,food intake and anal and nasal length of rats in each group were recorded once a week during the modeling period.The Lee’s index was calculated and the obesity model was evaluated.After successful establishment of the model,the rats in the hyperlipidemia group were randomly divided into model control group(n=8),electric stimulation group(n=8),swimming exercise group(n=8),western medicine Lipitor group(western medicine lipid-lowering group)(n=8),Hawthorn seed oil lipid-lowering group(Chinese medicine lipid-lowering group)(n=8),and each group was still given a high-fat diet.At the end of the 8th week of intervention,the rats in each group were killed and taken.The body weight and anal and nasal length of the rats in each group were measured and the Lee s index was calculated.The blood was taken from the tip of rat heart and the content of Total cholesterol(TC),Triglyceride(TG),Free fatty acid(FFA),Glycosylated hemoglobin(GHb)was measured by biochemical kit.The content of Insulin(INS),Leptin(LP),Resistin(Res)in rat serum was detected by ELISA kit.The histomorphological changes of hepatic lobule in rats were observed by HE staining.The morphological changes of mitochondria and apoptosis of related structures in rat liver cells were observed by transmission electron microscope.The mRNA levels of thalamic Protein tyrosine phosphatase-1B(PTP-1B),Suppressor of cytokine signaling-3(SOCS-3)and the expression of Leptin,Resistin protein in white adipose tissue were detected by RT-PCR assay.The relative expression of PTP-1B and SOCS-3 protein in rat hypothalamus was detected by;Western Blotting method.Results:1.1.After 8 weeks of high fat feeding,the body weight,Lee’s index and diet volume of rats in hyperlipidemia group were higher than those in normal control group(P<0.01),indicating that the obesity model was successful.Compared with the normal control group,the serum insulin,leptin,resistin content,glycosylated hemoglobin,fasting blood glucose and 2 h postmeal blood glucose in the hyperlipidemia group were higher than those in the normal control group(P<0.01),indicating that the obese rat model had leptin resistance at the same time.2.Changes in lipid metabolism in each group after 8 weeks of intervention.Compared with the normal control group,TC,TG,FFA:was increased in the other five groups(P<0.01).Compared with the model control group,the TC,TG,FFA of the other four groups was lower than that of the model control group(P<0.01).Compared with swimming group,TC,TG,FFA in electric stimulation group and western medicine lipid-lowering group was higher than that in swimming exercise group,but TC in traditional Chinese medicine lipid-lowering group was slightly higher than that in normal control group(P<0.05).There was no significant difference in TG.FFA between traditional Chinese medicine group and normal control group(P>0.05).3.HE staining and transmission electron microscope(TEM)results:Compared with the model control group,the morphology of liver tissue and cells in obese rats after swimming intervention was significantly improved,the central vein was obvious,the morphology of liver lobules was basically clear,the arrangement of liver cord was relatively regular,and the apoptotic cells were decreased.The number of lipid cells was small,the inflammatory infiltration was not obvious,and the arrangement of cells was relatively close.The cell structure was relatively complete and the phenomenon of apoptosis was not obvious.In the electrical stimulation group,the structure of liver tissue was relatively clear,the structure of hepatic lobule was basically recovered,the intracellular structure was relatively complete,and the number of mitochondria was decreased.In Hawthorn seed oil group,the structure of liver tissue was relatively complete and the morphology of liver lobule was basically nonnal.The prominent manifestation of Hawthorn seed oil group was that there was more fat accumulation in cells and the morphology of cells became larger.In Liputol group,the basic structure of liver was seen,endoplasmic reticulum dissolved significantly,mitochondria increased and partial fusion,and the morphology of cells was thin.4.Expression of Leptin,Resistin in white adipose tissue:Compared with the normal control group,the expression of Leptin,Resistin in white adipose tissue of the other five groups was higher than that of the normal control group(P<0.01).Compared with the model control group,the expression of Leptin and Resistin in white adipose tissue was significantly decreased in different intervention groups(P<0.01).There was no significant difference between the western medicine lipid lowering group and the swimming exercise group(P>0.05),but the electrical stimulation group and the traditional Chinese medicine lipid lowering group were significantly higher than those in the swimming exercise group(P<0.01).5.Relative mRNA level of PTP-1B and SOCS-3 in Hypothalamic neurons:Compared with the normal control group,the level of PTP-1B and SOCS-3 in the other five groups was higher than that in the control group(P<0.01).Compared with the model control group,the mRNA levels of PTP-1B and SOCS-3 in the other four groups were significantly decreased(P<0.01).Compared with swimming group,there was no significant difference in mRNA level of PTP-1B and SOCS-3 between western medicine group and swimming group(P>0.05).Inhibition of PTP-1 in Hypothalamic neurons in Electrical stimulation Group and traditional Chinese Medicine Fat-lowering Group The relative effect of mRNA level of B and SOCS-3 was not enough,which was significantly different from that of swimming group(P<0.05).Conclusions:1.Different intervention methods had obvious effects on improving leptin resistance and insulin sensitivity,among which swimming and western medicine lipid lowering group were better than transcutaneous acupoint electrical stimulation and traditional Chinese medicine lipid reduction group.2.The improvement of leptin resistance and insulin sensitivity is related to the down-regulation of PTP-1B and SOCS-3 protein expression and transcriptional activity in hypothalamus. 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