替米沙坦对体外培养THP-1源性巨噬细胞MMP-9与CD40/CD40L表达的影响

目的:通过观察替米沙坦对体外培养的THP-1源性巨噬细胞基质金属蛋白酶9(MMP-9)及白细胞分化抗原CD40/CD40L表达的影响,揭示替米沙坦抗炎作用的可能机制,同时明确替米沙坦的心血管保护作用。方法:用一定浓度的血管紧张素Ⅱ(AngⅡ)(10 000 nmol/L)诱导体外培养的巨噬细胞,与不同浓度的替米沙坦共同孵育,以MMP-9和CD40/CD40L为指标,应用RT-PCR方法分别检测MMP-9和CD40/CD40L mRNA表达。结果:替米沙坦可同时下调AngⅡ刺激后的MMP-9、CD40和CD40L mRNA的表达,有剂量依赖性。替米沙坦100 nmol/L、1 000 nmol/L、10 000 nmol/L时,MMP-9mRNA的表达与AngⅡ组相比分别下降24%、42%及62%;CD40、CD40LmRNA的表达与AngⅡ组相比分别下降24%、39%、55%、16%、32%及40%。结论:替米沙坦体可下调外培养巨噬细胞MMP-9的表达,从而具有抗炎及稳定斑块作用,其作用机制与抑制CD40/CD40L通路有关。

The affection of telmisartan on expression of CD40/CD40L and matrix metalloproteinase-9 in THP-1 cells which is cultured in vitro

Objective:To investigate the effect of telmisartan on expression of matrix metalloproteinase(MMP-9) and CD40/CD40L in THP-1 cells which is cultured in vitro,and reveal thepossible mechanism of anti-inflammatory effects of telmisartan,futhermore,clarify the cardiovascular protective effects of telmisartan.Methods:THP-1 cells were induced by fixed concentration of AngⅡ,and indcubated with different concentrations of telmisartan,MMP-9 and CD40/CD40L as an indicator,the MMP-9 and CD40/CD40L mRNA expression were detected by RT-PCR.Results: Telmisartan reduced both the expression of MMP-9 and CD40/CD40L mRNA which induced by AngⅡ and its role in a dose-dependent.Telmisartan 100/L,1000/L,10 000/L when the expression of MMP-9mRNA compared with AngⅡ group decreased 24%,42% and 62%,the expression of CD40,CD40L mRNA decreased 24%,39% and 55% and 16%,32% and 40%.Conclusion: Telmisartan reduced both the expression of MMP-9 in THP-1 cells which is cultured in vitro,which has anti-inflammatory and plaque stabilizing effect.The antagonism of telmisartan on the expression of MMP-9 is related to inhibit the CD40/CD40L pathway.