Regulatory Effect of Rac1 on Vascular Reactivity After Hemorrhagic Shock in Rats
Regulatory Effect of Rac1 on Vascular Reactivity After Hemorrhagic Shock in Rats
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Rac1对失血性休克大鼠血管反应性的调节作用
DOI：
10.1097/fjc.0b013e318215e21d
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发表时间：
2011-06
影响因子：
3
通讯作者：
Liu, Liangming
中科院分区：
文献类型：
--
作者：
Li, Tao;Yang, Guangming;Xu, Jing;Liu, Liangming
我们使用了分离自失血性休克大鼠的上级肠系膜动脉（SMA）和缺氧处理的血管平滑肌细胞（VSMCs;模拟休克状态），观察血小板衍生生长因子（PDGF; Rac 1刺激剂）和NSC 23766（Rac 1拮抗剂）对血管反应性的影响以及与Rho激酶-肌球蛋白轻链磷酸酶（MLCP）和p21激活激酶（PAK）-肌球蛋白轻链磷酸酶的关系链激酶（MLCK）信号通路。结果表明，休克早期或短暂缺氧后，平滑肌细胞和血管平滑肌细胞的收缩反应明显增强。NSC 23766（Rac 1拮抗剂）进一步增加SMA和VSMCs的收缩反应，而PDGF（Rac 1刺激剂）降低SMA和VSMCs的收缩反应。在休克后期或长时间缺氧时，SMA和VSMCs的收缩反应明显降低，NSC 23766增强SMA和VSMCs的收缩反应，而PDGF则进一步降低SMA和VSMCs的收缩反应。PDGF激活Rac 1可显著增加VSMCs中PAK和MLCP的活性，降低Rho激酶和MLCK活性以及20-kDa肌球蛋白轻链磷酸化。PAK抑制剂PAK-18显著拮抗PDGF诱导的MLCK活性降低，而Rho激酶拮抗剂Y-27632进一步加强PDGF诱导的MLCP活性增加。简单的液体复苏没有改善，但与NSC 23766组合显著改善了24小时的血管反应性和动物存活率。提示Rac 1对休克后血管反应性有抑制作用。Rac 1主要通过激活PAK、抑制MLCK和抑制Rho激酶来调节血管反应性，并将Rho激酶的抑制作用解包为MLCP。Rac 1可能是一个潜在的目标，以治疗血管低反应性在许多关键条件。
We used isolated superior mesenteric arteries (SMAs) from hemorrhagic-shock rats and hypoxia-treated vascular smooth muscle cells (VSMCs; mimicking the shock state) to observe the effects of platelet-derived growth factor (PDGF; Rac1 stimulator) and NSC23766 (Rac1 antagonist) on vascular reactivity and the relationship with the Rho kinase-myosin light-chain phosphatase (MLCP) and p21-activated kinase (PAK)-myosin light-chain kinase (MLCK) signal pathway. The results indicated that the contractile responses of the SMAs and VSMCs were significantly increased at early shock or after transient hypoxia. NSC23766 (Rac1 antagonist) further increased, whereas PDGF (Rac1 stimulator) decreased the contractile responses of SMAs and VSMCs. In the late period of shock or prolonged hypoxia, the contractile responses of SMAs and VSMCs were significantly decreased; NSC23766 increased (whereas PDGF further decreased) the contractile response of the SMAs and VSMCs. Activation of Rac1 with PDGF significantly increased the activity of PAK and MLCP, and decreased Rho kinase and MLCK activity and 20-kDa myosin light-chain phosphorylation in VSMCs. The PAK inhibitor PAK-18 significantly antagonized the PDGF-induced decrease in MLCK activity, whereas the Rho kinase antagonist Y-27632 further enforced the PDGF-induced increase in MLCP activity. Simple fluid resuscitation did not improve but in combination with NSC23766 significantly improved vascular reactivity and animal survival at 24 hours. This suggested that Rac1 has an inhibitory effect on vasoreactivity after shock. Rac1-mediated regulation of vascular reactivity is mainly through activation of PAK, inhibition of MLCK and inhibition of Rho kinase, unpack the inhibition of Rho kinase to MLCP. Rac1 may be a potential target to treat vascular hyporeactivity in many critical conditions.
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影响因子：
3.1
作者：
Tao Li;Liangming Liu;Jian-cang Liu;Jia Ming;Jing Xu;Guangming Yang;Yuan Zhang
通讯作者：
Tao Li;Liangming Liu;Jian-cang Liu;Jia Ming;Jing Xu;Guangming Yang;Yuan Zhang
影响因子：
3.1
作者：
K. Zhao;Xuliang Huang;Jie Liu;Qiaobing Huang;Chunhua Jin;Yong Jiang;Jian-qiu Jin;Gui-ling Zhao-
通讯作者：
K. Zhao;Xuliang Huang;Jie Liu;Qiaobing Huang;Chunhua Jin;Yong Jiang;Jian-qiu Jin;Gui-ling Zhao-
影响因子：
7.8
作者：
Tsuji, Takahiro;Ishizaki, Toshimasa;Okamoto, Muneo;Higashida, Chiharu;Kimura, Kazuhiro;Furuyashiki, Tomoyuki;Arakawa, Yoshiki;Birge, Raymond B;Nakamoto, Tetsuya;Hirai, Hisamaru;Narumiya, Shuh
通讯作者：
Narumiya, Shuh
影响因子：
3.1
作者：
Jia Ming;Tao Li;Yuan Zhang;Jing Xu;Guangming Yang;Liangming Liu
通讯作者：
Jia Ming;Tao Li;Yuan Zhang;Jing Xu;Guangming Yang;Liangming Liu
影响因子：
64.5
作者：
RIDLEY, AJ;PATERSON, HF;HALL, A
通讯作者：
HALL, A