| ObjectivesInsulin resistance(IR)is closely linked with many dieases,such as obesity,diabetes mellitus type 2(T2MD),polycystic ovary syndrome,metabolic disorders,hypertension,etc.And IR is the key pathogenes to the obese patients who developed T2 MD.It is necessary to intervene obesity in early stage,which can not only improve IR,but also prevent it from suffering T2 DM and related cardiovascular disease.In this study,the model of obese rats with IR was used.Mechanisms of the effect of electroacpuncture(EA)on Obese rats with IR were studied,via its regulation on hypothalamic SIRT1/FoxO1 and oxidative stress.It was expected to provide experimental evidence for application of EA in treatment of Obese patients with IR.MethodsThat 70 SPF male Wistar rats of eight weekswere randomly divided into normal group(n = 10)and high-fat feeding group(n = 60)after feeding adaptively for a week.In 8 weeks,That 3 rats in normal group and 18 in model group wererandomly selected to participate inhigh insulin-regularglucose clamps,and this was used to assess the model of IR,at the same time,weight of each rat and longth of anal-nose were mesureed,Lee 's index were calculated,both of which were used to evaluate the model of obesity.After Obese rats with IR were gotten successfully,rats in high-fat feeding group would be divided into model group,sham operation group,EA group,EA+ inhibitors group,inhibitors group,agonist group randomly,each group of seven.Normal group givennothing other than ordinary feed,model group given nothing other than high-fat feed,sham operation group were feed with high-fat fodder and were bulit in pipe at third ventricle and injected with artificial cerebrospinal fluid;EA group feed with high-fat fodder and given EA treatment at acupoint ST36,ST40,CV4 and CV12 for once every two days,frequency is 2Hz,electric current were set at 1mA,EA+inhibitors group were feed with high-fat fodder,and treated with EA,the specific treatment method is the same as EA group,what is more,bulit in pipe at third ventricle and injected with specificity inhibitors EX-527 of SIRT1,inhibitors group were feed with high-fatfodder and bulit in pipe at third ventricle and injected with specificity inhibitors EX-527 of SIRT1,agonistgroup were feed with high-fat fodder and bulit in pipe at third ventricle and injected with specificity agonist SRT1720 of SIRT1.After treatmented with six weeks,IPGTT and IPITT of each rat were measuredvia the tail vein.After treatmented with eight weeks,three rats in each group were randomly selected to participate in high insulin-regularglucose clamps,so GIR is measured,TC?TG?FFA were measured via biochemical kit,Leptin?Resistin of each rat were measured via Elisa kit,in addition,the expression of protein and mRNA of SIRT1?FoxO1 and CAT were measured via western blot and RT-PCR;than ROS?MDA and SOD were also measurd relevant kit.lastly all data would be analyzed statistically.Results1.The effect of high-fat fodder of eight weeks on the boby mass,Lee,s index and GIR,in Obese rats with IRThough feeding of eight weeks,the weight and Lee,s index in high-fat feeding group were significantly higher than that of nomal group(P<0.01),and GIR in high-fat feeding group weresignificantly lower than that of nomal group(P<0.01).2.Effects of EA on boby mass,the level of TC,TG,FFA,Leptin,Resistin,and insulin sensitivity in Obese rats with IRCompared with model group,the body mass of EA and agonist group were significantly declined(P<0.01),while that of inhibitors group were significantly rised(P<0.01);compared with EA+inhibitors group,the body mass of inhibitors group were rised(P<0.05),while that of EA group have no statistical significance(P>0.05).what is more,EA AND agonist group have on statistical significance(P>0.05).The level of TC,TG and FFA in EA and agonist group were significantly lower than that of model group(P<0.01),while that of inhibitors group were significantly higher(P<0.01);Compared with EA group,EA+ inhibitors group were significantly higher(P<0.01).The level of Leptin and Resistin in EA and agonist group were significantly lower than that of model grou(P<0.01),while that of inhibitors group were significantly higher(P<0.01).Compared with model group,the IPITT?IPGTT?GIR of in EA and agonist group were significantly strengthened than that of model group(P<0.01),whlie that of inhibitors group were significantly weakened(P<0.05);compared with EA+inhibitors group,that of inhibitors group were also significantly weakened(P<0.01).3.Effects of EA on protein and mRNA expression levels of hypothalamic SIRT1?FoxO1?CAT in Obese rats with IRCompared with normal group,levels of protein and mRNA expression of hypothalamic SIRT1?FoxO1?CAT in the other group were all lowerd(P<0.05);compared with model group,that of EA and agonist group were higher(P<0.05),while that of inhibitors group were lower(P<0.05);compared with EA group;that of EA+inhibitors group were lower(P<0.05).4.Effects of EA on levels of hypothalamic ROS,MDA and activity of SOD in Obese rats with IRCompared with normal group,the levels of hypothalamic ROS and MDA were significantly higher and the activity of SOD were significantly lower in the other group(P<0.01);compared with model group,the levels of hypothalamic ROS and MDA were significantly lower and the activity of SOD were significantly higher in EA and agonist group(P<0.01),while that of inhibitors group were oppositive(P<0.01);compared with EA group;the levels of hypothalamic ROS and MDA were significantly higher and the activity of SOD were significantly lower in EA+ inhi bitors group(P<0.01).Conclusions1.The level of boby mass,TC,TG,FFA,leptin and resistin in Obese rats with IR were reduced by EA,insulin sensitivity in Obese rats with IR also can be inhanced by EA at the same time.2.EA can upregulate protein expression and mRNA levels of hypothalamic SIRT1,FoxO1,CAT in Obese rats with IR,and the level of hypothalamic ROS and MDA can be reduced,and the activity of SOD can be strengthened by EA in Obese rats with IR... |
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