异丙酚介导的RhoA/ROCK2信号通路对脑缺血再灌注后神经炎症、细胞凋亡和脑梗死的作用

The effects of Propofol-mediated RhoA / ROCK2 signaling pathway on neuroinflammation, cell apoptosis and cerebral infarction after cerebral ischemia-reperfusion

目的探讨异丙酚对脑缺血再灌注大鼠神经炎症、细胞凋亡和脑梗死的作用与保护机制。方法将30只SD大鼠随机分为假手术(Sham)组、脑缺血再灌注(I/R)组和异丙酚(Propofol)组,Sham组与I/R组使用水合氯醛(300 mg/kg)麻醉,异丙酚组应用异丙酚(60mg/kg)麻醉;大脑中动脉闭塞造模2 h后恢复血供,24 h后进行神经功能缺损评分,取脑组织进行TTC染色、炎性细胞因子水平检测、免疫组化、Western blot实验。结果 I/R组大鼠神经功能受损,缺血侧梗死严重;Western Blot检测显示RhoA/ROCK2蛋白表达增加,Caspase-3蛋白剪切增加;免疫组化显示Iba1激活,GFAP活化,即神经炎症反应增加。此外,Nissl小体减少,TUNEL阳性细胞数增加,即神经元凋亡增加;异丙酚组RhoA/ROCK2蛋白表达水平、Caspase-3蛋白剪切显著降低,神经炎症反应减轻与神经元凋亡减少,神经功能缺损评分降低与脑梗死面积减少。结论异丙酚可能通过抑制RhoA/ROCK2信号通路来减轻脑中神经炎症反应和减少神经元凋亡,从而改善神经功能与脑部梗死情况。

Objective To explore the effects of propofol on neuroinflammation, cell apoptosis and cerebral infarction in rats with cerebral ischemia-reperfusion. Methods Thirty SD rats were randomly divided into SHAM group, ischemia/reperfusion(I/R) group and Propofol group. Sham group and I/R group were narcotized with chloral hydrate(300 mg/kg). Propofol group was anesthetized with propofol(60 mg/kg). The cerebral artery ischemia operation was performed and blood supply was restored 2 hours later. After 24 hours, neurological scores were obtained, and brain tissues were taken for TTC staining, kit detection, immunohistochemistry and Western blot experiments. Results In I/R group, the nerve function was damaged, and the ischemic side infarction was severe. Western Blot showed increased expression of RhoA/ROCK2 protein and increased cleavage of Caspase-3 protein. Immunohistochemical staining showed that Iba1 activation, GFAP activation which presented neuroinflammatory response increased. In addition, Nissl bodies decreased, TUNEL-positive cells increased, which presented increased neuronal apoptosis. However, the expression levels of RhoA/ROCK2 protein and Cleaved-Caspase-3 protein were significantly reduced in the Propofol group, the neuroinflammatory response and neuron apoptosis were reduced, the neural function score was reduced, and the area of cerebral infarction was reduced. Conclusion Propofol reduced neuroinflammation and neuronal apoptosis in the brain by inhibiting the RhoA/ROCK2 signaling pathway, improved neurological function and decreased cerebral infarction.