Polydatin improves atherosclerotic plaque and endothelial inflammation in atherosclerotic rats by inhibiting TGF-β/Smad signaling pathway
Objective:To investigate the improvement effect of polydatin on atherosclerotic(AS)plaque and endothelial in-flammation in AS rats by inhibiting transforming growth factor β(TGF-β)/Smad signaling pathway.Methods:Sixty rats were randomly divided into blank control group,model control group,low,medium and high dose polydatin groups and positive control group,with 10 rats in each group.The rats in the normal control group were fed with ordinary feed,and the rats in the other groups were used to prepare AS rat models by feeding with high-fat feed and intraperitoneally injected with vitamin D3.The rats in the low-dose,medium-dose and high-dose polydatin groups were given 40,80 and 160 mg/kg of polydatin by gavage every day,the rats in the positive control group were given 5 mg/kg of simvastatin by gavage every day,and the rats in the model control group and the blank control group were given the same amount of normal saline by gavage every day.After the administration,oil red O staining was used to observe the forma-tion of AS plaque in the rat aorta;automatic biochemical analyzer was used to detect the levels of rat triglyceride(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C);enzyme-linked immunosor-bent assay was used to detect the contents of tumor necrosis factor(TNF)-α,IL-6,IL-8,C-reactive protein(CRP),monocyte che-moattractant protein 1(MCP-1),homocysteine(Hcy),intercellular adhesion molecule 1(ICAM-1)and endothelin-1(ET-1)in se-rum;Western blot was used to detect the protein expression levels of TGF-β1,Smad2/3 and p-Smad2/3 in rats.Results:Compared with blank control group,a large number of AS plaques appeared on the inner wall of the aorta in the model control group,the levels of TG,TC,LDL-C,TNF-α,IL-6,IL-8,CRP,MCP-1,Hcy,ICAM and ET-1 in the serum were significantly increased,the level of HDL-C was significantly reduced,and the expression of TGF-β1 protein and the of p-Smad2/3/Smad2/3 in aortic tissue were signifi-cantly increased(P<0.05).The plaque area on the inner wall of the aorta of AS rats was significantly reduced after the intervention of polydatin,the levels of TG,TC,LDL-C,TNF-α,IL-6,IL-8,CRP,MCP-1,Hcy,ICAM,and ET-1 in the serum were significantly reduced,the level of HDL-C was significantly increased,the expression of TGF-β1 protein and the p-Smad2/3/Smad2/3 in aortic tissue were significantly reduced(P<0.05),and the changes of the above indexes were all dose-dependent(P<0.05).The levels of TC,LDL-C and HDL-C in the positive control group were not significantly different from those in the high dose polydatin group(P>0.05),while the other indexes were lower than those in the high dose polydatin group(P<0.05).Conclusion:Polydatin regulates blood lipids and reduces the expression of cellular inflammatory factors to reduce the formation of AS plaques and improve inflamma-tion in AS rats,and the mechanism is related to the inhibition of the TGF-β/Smad signaling pathway.
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