H2S舒张大鼠脑血管作用与RhoA及ROCK关系的研究

Study on relationship between H 2S-induced vasodilatationof rat cerebral basilar artery and RhoA as well as ROCK

目的研究H2S舒张大鼠脑血管作用与RhoA和ROCK的关系。方法利用离体微血管压力直径测定法检测大鼠脑基底动脉(CBA)的舒张作用,用RhoA抑制剂C3预处理后抑制RhoA活性,用siRNA转染技术在体敲低大鼠ROCK1和ROCK2表达。结果在1×10^-6~1×10^-3 mol·L^-1范围内,NaHS呈浓度依赖性地诱导大鼠CBA舒张,但这种舒张作用可被1×10^-5mol·L^-1C3预处理明显减弱;ROCK1-siRNA或ROCK2-siRNA在体转染均可明显地敲低大鼠CBA中的ROCK1或ROCK2表达;在ROCK1或ROCK2表达敲低的大鼠CBA上,NaH S诱导的血管舒张作用有明显的降低。结论 H2S通过作用于RhoA、ROCK1和ROCK2导致RhoA-ROCK信号通路的抑制来发挥舒张大鼠脑血管作用。

Aim To study the relationship between H 2S-induced vasodilatation of rat cerebral basilar artery and RhoA as well as ROCK.Methods The relaxation effect of rat cerebral basilar artery(CBA)was detected by microvascular pressure diameter assay in vitro.The activity of RhoA was inhibited by pretreatment with RhoA inhibitor C3,and ROCK 1 and ROCK 2 protein expressions were knocked down in vivo with siRNA technique.Results In the range of 1×10^-6~1×10^-3 mol·L^-1,NaHS induced a relaxation of rat CBA in a concentration-dependent manner,which,however,was significantly weakened by pretreatment of C31×10^-5 mol·L^-1;transfection of ROCK 1-siRNA or ROCK 2-siRNA in vivo could significantly knock down ROCK 1 or ROCK 2 protein expression in rat CBA;in rat CBA of ROCK 1 or ROCK 2 knockdown,relaxation of NaHS was significantly attenuated.Conclusions By acting on RhoA,ROCK 1 as well as ROCK 2,H 2S leads to the inhibition of RhoA-ROCK signaling pathway to produce dilation of cerebral artery in rats.