替米沙坦对同型半胱氨酸诱导内皮细胞炎症损伤及对p38MAPK通路的影响

Effects of Telmisartan on Homocysteine-Induced Endothelial Cell Inflammation and p38MAPK Pathway

目的:探讨替米沙坦对同型半胱氨酸诱导内皮细胞炎症损伤及对p38MAPK通路的影响。方法:设MS-1内皮细胞组(MS-1内皮细胞)、同型半胱氨酸组(5 mg·L^(-1)同型半胱氨酸+MS-1内皮细胞)、替米沙坦组(5 mg·L^(-1)同型半胱氨酸+50 mg·L^(-1)替米沙坦+MS-1内皮细胞),培养结束后,检测各组细胞活力和凋亡率、G1期水平、白细胞介素-2(IL-2)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)蛋白表达水平、p-p38MAPK mRNA及蛋白水平、半胱氨酸蛋白酶-3(caspase-3)、半胱氨酸蛋白酶-6(caspase-6)、半胱氨酸蛋白酶-9(caspase-9)蛋白表达水平。结果:与MS-1内皮细胞组比较,同型半胱氨酸组和替米沙坦组活力、G1期水平显著降低(P <0. 05);凋亡率、IL-2、IL-6、TNF-α蛋白水平、p-p38MAPK mRNA及蛋白水平、caspase-3、caspase-6、caspase-9蛋白水平显著升高(P <0. 05)。与同型半胱氨酸组比较,替米沙坦组活力、G1期水平显著升高(P <0. 05);凋亡率、IL-2、IL-6、TNF-α蛋白水平、p-p38MAPK mRNA及蛋白水平、caspase-3、caspase-6、caspase-9蛋白水平显著降低(P <0. 05)。结论:替米沙坦对同型半胱氨酸诱导的内皮细胞炎症损伤具有保护作用,其机制与替米沙坦抑制p38MAPK炎症信号通路的激活及抑制内皮细胞凋亡有关。

Objective:To investigate the effects of telmisartan on homocysteine-induced endothelial cell inflammation and p38 MAPK pathway.Methods:The cells were divided into MS^-1 endothelial cell group(MS^-1 endothelial cells),homocysteine group(5 mg·L^-1 homocysteine+MS^-1 endothelial cells)and telmisartan group(5 mg·L^-1 homocysteine+50 mg·L^-1 telmisartan+MS^-1 endothelial cells).After the culture,the viability,apoptosis rate,cells arrested at G1 phase,IL-2,IL-6,TNF-αprotein expression,mRNA and protein expression levels of p-p38 MAPK,as well as the protein expression levels of caspase-3,caspase-6 and caspase-9 were detected.Results:Compared with those in MS^-1 endothelial cell group,the cell viability and G1 level in homocysteine group and telmisartan group were significantly decreased(P<0.05),and the apoptosis rate,protein expression levels of IL-2,IL-6 and TNF-α,mRNA and protein expression levels of p-p38 MAPK,as well as the protein expression levels of caspase-3,caspase-6 and caspase-9 were significantly increased(P<0.05).Compared with those in homocysteine group,the cell viability and G1 level in telmisartan group were significantly increased(P<0.05),and the apoptosis rate,protein expression levels of IL-2,IL-6 and TNF-α,mRNA and protein expression levels of p-p38 MAPK,as well as the protein expression levels of caspase-3,caspase-6 and caspase-9 were significantly decreased(P<0.05).Conclusion:The protective effect of telmisartan on homocysteine-induced endothelial cell inflammatory injury is related to the inhibition of p38 MAPK inflammatory signaling pathway activation and endothelial cell apoptosis.