Protective effect of ropivacaine on gestational diabetes mellitus rats by regulating SIRT1/AMPK signaling pathway
Objective To investigate the protective effect of ropivacaine on gestational diabetes mellitus(GDM)rats by regulating the silent information regulator factor 2 related enzyme 1(SIRT1)/AMP-activated protein kinase(AMPK).Methods Female rats were fed with high fat and high sugar for 8 weeks before being caged with male rats to obtain pregnant rats.The sixth day of pregnancy,STZ was injected intraperitoneally to prepare a GDM rat model.The successfully modeled rats were randomly grouped into a model group,a low-dose ropivacaine group(1 mg/kg),a high-dose ropivacaine group(2.0 mg/kg),and a high-dose ropivacaine(2.0 mg/kg)+EX-527(1 mg/kg)group.A control group was also established,with 15 rats in each group.The activities of glutamic pyruvic transami-nase(GPT),glutamic oxaloacetic transaminase(GOT)and alkaline phosphatase(ALP),and the contents of TC,TG,LDL-C and HDL-C in rat serum were detected by automatic biochemical analyzer;HE staining was applied to observe the histopathology of the liver;ELISA method was applied to detect serum levels of TNF-α,IL-6,and IL-1β;the commercial reagent kits were applied to detect the levels of MDA,SOD,and GSH in liver tissue;West-ern blot was applied to detect the levels of Bcl-2,Bax,SIRT1,and AMPK proteins in liver tissue.Results The morphology and structure of liver histiocyte in the control group were normal;compared with the control group,the liver tissue of rats in the model group showed obvious fat vacuoles and infiltration of inflammatory cells,the levels of serum TG,TC,LDL-C,GPT,GOT,ALP,TNF-α,IL-6,and IL-1β,liver tissue MDA,and Bax in rats were ob-viously increased,the levels of serum HDL-C,liver tissue SOD,GSH,Bcl-2,SIRT1,p-AMPK/AMPK were obvi-ously reduced(P＜0.05);compared with the model group,the fat vacuoles in the low-dose and high-dose ropiva-caine groups were obviously reduced,with a small amount of inflammatory cell infiltration,the levels of serum TG,TC,LDL-C,GPT,GOT,ALP,TNF-α,IL-6,and IL-1β,liver tissue MDA,and Bax in rats were obviously re-duced,the levels of serum HDL-C,liver tissue SOD,GSH,Bcl-2,SIRT1,p-AMPK/AMPK were obviously in-creased(P＜0.05);compared with the high-dose ropivacaine group,EX-527 intervention can reduce the protective effect of ropivacaine on GDM rats.Conclusion Ropivacaine can reduce inflammation and oxidative stress in GDM rats by activating the SIRT1/AMPK signaling pathway,thereby improving GDM symptoms.
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