Study On The Mechanism Of SirT1 Activator Slowing Down The Progression Of Lupus Nephritis By Regulating Nlrp3

Objective:1.To clarify the therapeutic effect of SirT1 agonist resveratrol on lupus nephritis in MRL /lpr mice.2.To observe the effects of resveratrol on oxidative stress level,NLRP3 expression and related inflammatory factors secretion in lupus nephritis mice,and to explore the specific mechanism of SirT1 agonist protecting kidney,so as to provide new ideas for the treatment of lupus nephritis.Method:Ten weeks old MRL / lpr mice were randomly divided into 3 groups: model group(MRL/lpr mice,Model group),resveratrol group(Res group)and conventional treatment group(dexamethasone group,Dex group),with 8 mice in each group;BALB/C female mice of the same week old were used as normal control group(control group).Resveratrol was given by gavage in Res group once a day for 8 weeks,dexamethasone was given by gavage in Dex group,and saline was given by gavage in Model group and Control group.The body weight of MRL/lpr mice was measured weekly;One day before drug intervention and at the end of 2,4,6 and 8 weeks after drug intervention,24-hour urine of mice in each group was collected by metabolic cage,and 24-hour urine protein was detected by automatic biochemical analyzer.Anti-ds DNA antibody was detected by ELISA;the pathological changes of kindney were observed by HE,PAS and Masson staining;oxidative stress indexes(SOD,ROS,MDA)were detected by test kit;the expressions of SirT1 and NLRP3 were detected by immunohistochemistry;the gene and protein expressions of SirT1,inflammasome NLRP3 and Caspase1 that the downstream factor of NLRP3 and each inflammatory factors(IL-1β,IL-18,IL-6,IL-10)were detected by real-time PCR and Western blot.Result:Compared with the control group,resveratrol had no significant effect on the weight of mice with lupus nephritis.Compared with the model group,TP,BUN and Scr in resveratrol group returned to normal after drug intervention,with significant difference(p < 0.05);the level of Anti-ds DNA decreased significantly(p < 0.01),and the urine protein decreased significantly after 6 weeks of intervention(p < 0.01).Pathological results showed that the proliferation of mesangial cells and matrix was reducedand inflammatory cell infiltration and fibrosis were significantly inhibited after resveratrol treatment.Resveratrol can regulate renal oxidative stress,reduce the level of oxidative stress effectively,and significantly reduce the expression of NLRP3.Real-time PCR and Western blot results showed that resveratrol could activate SirT1,reduce the high expression of NLRP3,caspase1 and inflammatory factors(IL-1 β,IL-18,IL-6)genes and proteins,and significantly increase the expression of IL-10 significantly.Conclusion:1.SirT1 agonist resveratrol has therapeutic effect on lupus nephritis in MRL / lpr mice,and can alleviate the development of the lupus nephritis in mice effectively.2.The high expression of SirT1 in the mice model can protect the kidney by regulating the level of oxidative stress,inhibiting the expression of NLRP3 and further regulating the expression of inflammatory factors.