基于Rho/Rho-kinase信号通路探讨丙泊酚减轻大鼠脑缺血再灌注损伤的效果

Effect of propofol on cerebral ischemia-reperfusion injury in rats through the Rho/Rho kinase signaling pathway

目的基于Rho/Rho-kinase信号通路探讨丙泊酚减轻大鼠脑缺血再灌注损伤的效果。方法 SD大鼠100只分成:对照组、模型组、丙泊酚低、中、高剂量组(20.0、40.0、80.0 mg/kg),模型组、丙泊酚低、中、高剂量组建立脑缺血再灌注损伤模型,建模成功后,丙泊酚低、中、高剂量组给予相应剂量丙泊酚灌胃,对照组和模型组给予等体积生理盐水,持续给予4周,实验结束后,对每只大鼠进行神经功能缺损评分,行贴纸去除及平衡木行走实验,对大鼠海马区进行病理评分,同时测定大鼠脑组织中Rho、Rho-kinase mRNA和蛋白水平。结果模型组神经功能缺损评分、双侧贴纸去除时间、平衡木过杆时间、海马组织病理评分、脑组织海马区Rho、Rho-kinase mRNA和蛋白表达水平明显高于对照组(P<0.05);丙泊酚各剂量组神经功能缺损评分、双侧贴纸去除时间、平衡木过杆时间、海马组织病理评分、脑组织海马区Rho、Rho-kinase mRNA和蛋白表达水平明显低于模型组(P<0.05);且随着丙泊酚给药剂量的增加,神经功能缺损评分、双侧贴纸去除时间、平衡木过杆时间、海马组织病理评分、脑组织海马区Rho、Rho-kinase mRNA和蛋白表达水平逐渐降低,剂量-效应关系明显(P<0.05)。对照组海马区神经元细胞完整,排列紧密;模型组海马区神经元排列松散,细胞深染固缩,有片状坏死,神经细胞间质隔离;丙泊酚高剂组神经元细胞趋于正常;丙泊酚中、低剂量组较模型组而言,神经细胞疏松、固缩程度轻,神经元细胞核仁清楚可见。结论丙泊酚能减轻大鼠脑缺血再灌注神经功能损伤;其机制与丙泊酚能抑制Rho、Rho-kinase mRNA和蛋白的表达进而抑制Rho/Rho-kinase信号通路的激活有关。

Objective To investigate the effect of propofol on cerebral ischemia-reperfusion injury in rats through the Rho/Rho kinase signaling pathway.Methods One hundred SD rats were divided into control,model,and propofol low,medium,and high dose(20,40,and 80 mg/kg)groups.Rats in the model and propofol low,medium,and high dose groups were used to establish a cerebral ischemia-reperfusion injury model.After successful modeling,rats in propofol low,medium,and high dose groups were administered the corresponding dose of propofol and rats in control and model groups were administered the same volume of normal saline for 4 weeks.Then,each rat was scored for neurological deficits,stickers were removed,and balance beam walking experiments were performed.Pathological scores in the hippocampus of rats were calculated.Rho and Rho kinase mRNA and protein levels were determined in rat brain tissue.Results The neurological deficit score,bilateral sticker removal time,balance beam time,pathological score of the hippocampus,and Rho and Rho kinase mRNA and protein expression levels in the model group were significantly higher than those in the control group(P<0.05).The neurological deficit score,bilateral sticker removal time,balance beam time,pathological score of the hippocampus,and Rho and Rho kinase mRNA and protein expression levels in all propofol groups were significantly lower than those in the model group(P<0.05).With the increase of the propofol dose,the neurological deficit score,the time of side sticker removal,balance beam time,pathological score of the hippocampus,and Rho and Rho kinase m RNA and protein expression levels were decreased gradually and dose-response relationships were obvious(P<0.05).In the control group,neuronal cells were intact with a normal structure,clear staining,and oval nucleus in the center.In the model group,a large number of necrotic neurons were seen with obvious cell loss and nuclear pyknosis.In the high dose propofol group,a small number of necrotic neuronal cells were seen,the neuronal cell structure was relatively complete,and the nuclei of neurons were oval in the center.Compared with the model group,the numbers of necrotic neurons were decreased in middle and low dose propofol groups,but the meridians were loose and disordered,the nucleus exhibited pyknosis,and loss was obvious.Conclusions Propofol reduces neurological damage in rats with cerebral ischemia-reperfusion injury.The mechanism is related to inhibition of Rho and Rho kinase m RNA and protein expression by propofol and thus inhibition of activation of the Rho/Rho kinase signaling pathway.