胱硫醚-γ-裂解酶产生的H_(2)S在小鼠脑缺血/再灌注损伤中的作用及与RhoA-ROCK_(2)信号通路的关系  

Role of H_(2)S produced by CSE in cerebral ischemia-reperfusion injury in mice and its relationship with RhoA-ROCK_(2)signaling pathway

作　　者：郭芳芳 陈志武[1] GUO Fang-fang;CHEN Zhi-wu(Dept of Pharmacology,College of Basic Medicine,Anhui Medical University,Hefei 230032,China)

机构地区：[1]安徽医科大学基础医学院药理教研室,安徽合肥230032

出　　处：《中国药理学通报》2022年第9期1369-1374,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81973510,81374002)。

摘　　要：目的探讨胱硫醚-γ-裂解酶产生的H_(2)S在脑缺血/再灌注(cerebral ischemia/reperfusion,I/R)损伤中的作用及与RhoA-ROCK_(2)信号通路的关系。方法采用双侧颈总动脉结扎制备小鼠脑缺血/再灌注损伤模型,激光散斑法检测脑血流量,HE染色法观察脑海马组织病理学变化,检测LDH、NSE、RhoA和ROCK_(2)活性及H_(2)S含量和ROCK_(2)蛋白表达。结果H_(2)S合酶CSE底物L-Cys(300 mg·kg^(-1))可明显促进脑I/R小鼠脑血流量的恢复,改善海马组织的病理损伤,抑制血清中LDH活性和脑组织中NSE、RhoA及ROCK_(2)活性的升高,并抑制血清H_(2)S含量的降低和脑组织中ROCK_(2)蛋白表达的增多。但L-Cys上述作用可被CSE合酶抑制剂PPG(50 mg·kg^(-1))明显地减弱;H_(2)S供体NaHS(4.8 mg·kg^(-1))也有与L-Cys相同的上述作用。结论CSE产生的H_(2)S对小鼠脑I/R损伤有保护作用,其作用可能与抑制RhoA-ROCK信号通路及增加脑血流量有关。Aim To investigate the role of H_(2)S produced by CSE in cerebral ischemia-reperfusion(I/R)injury and its relationship with RhoA-ROCK_(2) signaling pathway.Methods Bilateral common carotid artery ligation was used to prepare a mouse cerebral ischemia-reperfusion injury model.Laser speckle method was used to detect cerebral blood flow,HE staining method was used to observe the pathological changes of brain hippocampus,and the activity of LDH,NSE,RhoA and ROCK_(2),H_(2)S content and ROCK_(2)protein expression were detected.Results The H_(2)S synthase CSE substrate L-Cys(300 mg·kg^(-1))could significantly promote the recovery of cerebral blood flow in brain I/R mice,improve the pathological damage of hippocampus,inhibit the increase of LDH activity in serum and NSE,RhoA and ROCK_(2) activity in brain tissues,and inhibit the decrease of serum H_(2)S content and the increase of ROCK_(2) protein expression in brain tissues.But the above effects of L-Cys could be significantly attenuated by the CSE inhibitor PPG(50 mg·kg^(-1));the H_(2)S donor NaHS(4.8 mg·kg^(-1))also had the same effect as L-Cys did.Conclusions H_(2)S produced by CSE has a protective effect on mouse brain I/R injury,and its effect may be related to inhibiting RhoA-ROCK signaling pathway and increasing cerebral blood flow.

关 键 词：硫化氢 胱硫氨酸-γ-裂解酶 脑缺血/再灌注 RhoA-ROCK_(2)信号通路 脑血流量 半胱氨酸 

分 类 号：R-332[医药卫生] R322.81R329.25R743.31R916.3