严重创伤、休克存在血管低反应性，这种血管低反应性严重影响休克等临床危重病症的发生、发展及治疗。我们前期研究发现休克后不同时相点miR141的变化与血管反应性变化间呈显著负相关，miR141对RhoA、Rac1蛋白表达具有明显调节作用，结合本人前一国家自然科学基金证实RhoA、Rac1在休克血管反应性调节中的重要作用，推测miR141可能通过RhoA、Rac1参与对休克血管反应性的调节，有不同机制参与对它们的调控，对RhoA的调节可能主要通过mRNA 3'UTR，对Rac1的调节可能主要通过调节DNA甲基化来实现。为此本课题拟取失血性休克大鼠，293T细胞，血管平滑肌细胞，研究miR141对休克血管反应性的调节作用与RhoA、Rac1的关系；miR141调节RhoA、Rac1机制，包括mRNA和DNA水平。通过该研究拟进一步阐述创伤休克等血管反应性的调节机制，为创伤休克等的治疗提供新的靶点。

Vascular reactivity exists in clinical condition such as severe trauma and shock,this reduced vascular reactivity severely interferes with the treatment of shock and other clinical critical conditions,particularly for the application of vaso-active agents. Our previous studies advocated from NSFC demonstrated that RhoA and Rac1 played important roles in the occurrence of vascular hypo-reactivity after shock. The changes of miR141 were negatively correlated with vascular reactivity after shock, and miR141 diminished the protein expression of RhoA and Rac1. We hypothesize that miR141 participates in the occurrence of vascular hypo-reactivity via regulation of RhoA and Rac1. The mechanisms may be related with its interaction with mRNA 3` UTR for RhoA or regulating DNA methylation for Rac1. To test this hypothesis, with hemorrhagic shock model, 293T cell and vascular smooth muscle cell, we will study the role of miR141 in the regulation of vascular reactivity following shock and the relationship to RhoA and Rac1, and the regulating mechanisms of miR141 on the expression of RhoA and Rac1. The objective is tended to intensify the mechanism of vascular hypo-reactivity, provide the new modulation targets for the treatment fo shock.