丹参酮ⅡA磺酸钠对尿毒症毒素作用下人脐静脉内皮细胞功能的影响OA北大核心CSTPCD

Objective:To discuss the effect of sodium tanshinone ⅡA sulfonate(STS)on the function of human umbilical vein endothelial cells(hUVECs)after treated with uremic toxin,and to clarify its mechanism.Methods:The hUVECs were passaged and divided into blank control group,uremic toxin-stimulation group,uremic toxin + STS group,and uremic toxin + STS + extracellular signal-regulated kinase(ERK)inhibitor group.The concentration of STS used in the last two groups was 10 mg·L-1.The shear stress stimulation at 12 dyn·cm-2 was applied to the cells in various groups.The proliferation activities of the cells in various groups were detected by CCK-8 assay;the expression levels of ERK,nuclear factor kappa B(NF-κB),and type Ⅰ collagen proteins in the cells in various groups were detected by Western blotting method;the expression levels of ERK,NF-κB,and type Ⅰ collagen mRNA in the cells in various groups were detected by real-time fluorescence quantitative PCR(RT-qPCR)method;the apoptotic rates the cells in various groups were detected by TUNEL method.Results:The CCK-8 assay results showed that after treated with shear stress,the probiferation activitres of the cells in uremic toxin-stimulation group and uremic toxin + STS + ERK inhibitor group were lower than that in uremic toxin + STS group(P<0.01).The Western blotting results showed that compared with uremic toxin group,the expression levels of ERK,NF-κB,and type Ⅰ collagen proteins in the cells in uremic toxin + STS group were increased(P<0.01).After inhibiting the ERK pathway,compared with blank control group,uremic toxin group,and uremic toxin + STS group,the expression levels of ERK,NF-κB,and type Ⅰ collagen proteins in the cells in uremic toxin + STS + ERK inhibitor group were significantly decreased(P<0.01).The RT-qPCR results showed that compared with uremic toxin group,the expression levels of ERK,NF-κB,and type Ⅰ collagen mRNA in the cells in uremic toxin + STS group were increased(P<0.01).After inhibiting the ERK signaling pathway,compared with blank control group,uremic toxin group,and uremic toxin + STS group,the expression levels of ERK,NF-κB,and type Ⅰ collagen mRNA in the cells in uremic toxin + STS + ERK inhibitor group were significantly decreased(P<0.01).The TUNEL method detection results showed that the apoptotic rate in the cells in uremic toxin + STS group was lower than those in uremic toxin-stimulation group and uremic toxin + STS + ERK inhibitor group(P<0.05).Conclusion:A certain concentration of STS can improve the proliferation of the endothelial cells and reduce the apoptosis of the cells after treated with uremic toxins by modulating the expressions of NF-κB and type Ⅰ collagen mRNA and proteins through the ERK signaling pathway.