Rhubarb sugar pills attenuate inflammatory response in large blood ves-sels of diabetic rats by regulating PI3K-Akt/NF-κB signaling pathway
AIM:To explore the mechanism of rhubarb sugar pills(RSP)in preventing and treating inflamma-tory response in large blood vessels of Zucker diabetic fatty(ZDF)rats based on phosphatidylinositol 3-kinase(PI3K)-pro-tein kinase B(PKB/Akt)/nuclear factor-κB(NF-κB)signaling pathway.METHODS:Fifteen male ZDF(fa/+)rats were used as the control group,and 75 male ZDF(fa/fa)rats fed with high-fat diet were randomly divided into model group,high-,medium-and low-dose RSP groups,and metformin group,with 15 rats in each group.After 12 weeks of drug inter-vention,the rats were euthanized,and the serum levels of high-density lipoprotein cholesterol(HDL-C),low-density lipo-protein cholesterol(LDL-C),triglyceride(TG)and total cholesterol(TC)were measured.The serum levels of CD4,in-terleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)were detected by ELISA.The pathological changes of abdominal aorta tissue was observed by HE staining.Immunohistochemistry was conducted to assess the expression of monocyte che-moattractant protein-1(MCP-1)in the abdominal aorta.The mRNA expression of PI3K,Akt and NF-κB p65 in the ab-dominal aorta was measured by RT-qPCR.Western blot was utilized to observe the protein levels of PI3K,Akt,p-Akt,p-IκB and NF-κB p65 in the abdominal aorta.RESULTS:Compared with model group,RSP significantly reduced fasting blood glucose,LDL-C,TG and TC levels in diabetic rats(P<0.05),and elevated HDL-C levels(P<0.05 or P<0.01).Treatment with RSP also significantly decreased the expression of inflammatory mediators in the serum of diabetic rats,with significant decreases in IL-6,TNF-α and CD4 levels(P<0.05 or P<0.01).The pathological damage in the abdomi-nal aorta tissue was significantly reduced,and the mRNA and protein levels of PI3K,Akt and NF-κB p65,as well as MCP-1,p-Akt and p-IκB protein levels,were all significantly decreased after RSP intervention(P<0.05 or P<0.01).CONCLUSION:Treatment with RSP can lower blood sugar and regulate lipids,thereby alleviating inflammatory damage in large blood vessels of diabetic rats.The mechanism may be related to the inhibition of PI3K-Akt/NF-κB signaling path-way activation and the attenuation of inflammatory response.
国家科技期刊平台
NSTL
万方数据
维普
