Research On The Mechanism Of Renal Denervationin Insulin Resistant Treatment

Objective This experiment aims to observe the effects of RDN on insulin resistance and skeletal muscle mitochondrial function in spontaneous diabetes ZDF rats.Methods 6 SPF healthy male ZDF(fa/+)rats were selected as control group,12 healthy males ZDF(fa/fa)rats were randomly divided into sham group and RDN group.After 3 days of adaptive feed,all the rats in the control group rats started common feed,sham and RDN group rats were accepted high fat feed(purina# 5008 high fat feed: protein 23.7.75%,total fat 55%,crude fiber,4.00%,digestive 14.6KJ/kg).After 6 weeks,the diabetes model were established successfully.In the sham group and RDN group,the rats were treated with sham operation or bilateral renal sympathetic denervation respectively.Post-operation weight and blood glucose were observed.Insulin sensitivity was observed in all rats with Hyperinsulinemic-euglycemic clamp test 2 weeks after RDN.The plasma NE and renal NE levels were detected by ELISA,and skeletal muscle ATPsyn,COXIV,UCP3 and SOD2 were tested by Western-blot method.Serum insulin and lipid levels were detected by bioassay test.Results After 6 weeks,the rats fed with high fat diet(HFD group)had significant increase in the weight and blood glucose when compared with control group fed with normal chow diet(NCD).Furthermore,2 weeks after RDN,the blood glucose level of the RDN group decreased significantly(P=0.000)when compared with the sham group.Hyperinsulinemic-euglycemic clamp test was performed 2 weeks after RDN.The glucose infusion rate(GIR)in HFD group decreased significantly when compared with the NCD group(P=0.000).Similarly,after RDN procedure,the GIR in RDN group increased significantly when compared with sham group(P=0.000).The level of norepinephrine(NE)was significantly decreased in RDN group when compared with the sham group(P=0.000).ATPsyn,COXIV which were the key enzyme of oxidative metabolism in skeletal muscle mitochondria decreased significantly in the HFD group when compared with NCD group(P = 0.001).However,parameters improved dramatically after RDN(P=0.001).As the main components in mitochondrial antioxidant system,the levels of UCP3 and SOD2 inHFD group were lower than NCD group(P=0.001).After RDN the parameters get improved significantly(P=0.001).Conclusion Our results showed that RDN improved the insulin sensitivity in diabetes rats.The mechanism may be related to the decrease of oxidative stress and function improvement in skeletal muscle mitochondrial by RDN.