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.

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 toxinstimulation 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. [ABSTRACT FROM AUTHOR]