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Effect of tanshinone ⅡA on function of human umbilical vein endothelial cells after treated with uremic toxin
Lihua WANG,Lan JIA,Haiyan CHEN,Bo YANG,Zhe WANG,Xueqing BI
PDF(2221 KB)
PDF(2221 KB)
Effect of tanshinone ⅡA on function of human umbilical vein endothelial cells after treated with uremic toxin
),Lan JIA1,Haiyan CHEN1,Bo YANG2,Zhe WANG1,Xueqing BI1Objective 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.
Hemodialysis / Arterial-venous fistula / Human umbilical vein endothelial cell / Uremia / Sodium tanshinone ⅡA sulphonase
R459.5
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