利多卡因调节RhoA/ROCK信号通路对缺血性脑卒中大鼠的神经保护作用

Neuroprotective effect of lidocaine on ischemic stroke rats by regulating the RhoA/ROCK signaling pathway

目的探讨利多卡因调节RhoA/ROCK信号通路对缺血性脑卒中(IS)大鼠神经保护作用。方法通过线栓法建立模型IS大鼠,随机分为模型组、利多卡因低(利多卡因-L,5 mg/kg)、中(利多卡因-M,10 mg/kg)、高剂量(利多卡因-H,20 mg/kg)组以及利多卡因-H+溶血磷脂酸(LPA)(20 mg/kg利多卡因+50μmoL/L LPA)组,以仅分离但不插尼龙线的大鼠为假手术组;干预结束后,对大鼠进行神经功能评分、脑梗死体积、脑含水量测定;分离脑组织,观察神经元变化、神经细胞凋亡以及RhoA、ROCK蛋白表达。结果与假手术组相比,模型组大鼠Zea-Longa评分(3.28±0.33、0.14±0.02)、脑梗死体积(38.09±3.81、0.00±0.00)、含水量(84.11±2.39、62.95±0.65)、神经细胞凋亡率(39.51±3.96、5.14±0.52)、RhoA(1.16±0.12、0.24±0.03)、ROCK蛋白(2.15±0.22、0.77±0.08)表达增加(P<0.05);与模型组相比,利多卡因组大鼠Zea-Longa评分(2.37±0.24、1.52±0.16、0.87±0.09)、脑梗死体积(27.42±2.76、16.64±1.68、8.22±0.83)、含水量(75.24±1.46、68.34±1.02、63.15±0.86)、神经细胞凋亡率(27.08±2.71、18.84±1.89、9.47±0.95)、RhoA(0.78±0.08、0.52±0.06、0.26±0.03)、ROCK蛋白(1.66±0.17、1.24±0.13、0.86±0.09)表达显著降低,组间差异有统计学意义(P<0.05);LPA逆转了利多卡因-H对IS大鼠的保护作用。结论利多卡因通过抑制RhoA/ROCK信号通路对IS大鼠发挥神经保护作用。

Objective To investigate the neuroprotective effect of lidocaine on ischemic stroke(IS)rats by regulating the RhoA/ROCK signaling pathway.Methods A model of IS rats was established by thread occlusion method and randomly separated into model group,lidocaine low(lidocaine-L,5 mg/kg),medium(lidocaine-M,10 mg/kg),high-dose(lidocaine-H,20 mg/kg)groups,and lidocaine-H+Lysophosphatidic acid(LPA)(20 mg/kg lidocaine+50μmoL/L LPA)group,rats that were separated but not inserted with nylon thread were in the sham operation group,after the intervention,the neurological function score,cerebral infarction volume,and brain water content of the rats were measured;brain tissue was isolated,and changes in neurons,neuronal apoptosis,and expression of RhoA and ROCK proteins were observed.Results Compared to the sham group,Zea-Longa score(3.28±0.33,0.14±0.02),cerebral infarction volume(38.09±3.81,0.00±0.00),water content(84.11±2.39,62.95±0.65),apoptosis rate(39.51±3.96,5.14±0.5)in model group 2,RhoA(1.16±0.12,0.24±0.03),ROCK protein(2.15±0.22,0.77±0.08)were increased(P<0.05);Compared to the model group,Zea-Longa score(2.37±0.24,1.52±0.16,0.87±0.09),cerebral infarction volume(27.42±2.76,16.64±1.68,8.22±0.83),water content(75.24±1.46,68.34±1.02,63.15)in lidocaine group±0.86,neuronal apoptosis rate(27.08±2.71,18.84±1.89,9.47±0.95),RhoA(0.78±0.08,0.52±0.06,0.26±0.03),R0CK protein(1.66±0.17,1.24±0.13,0.86±0.09)The expression was significantly decreased and there were differences between groups(P<0.05);LPA reversed the protective effect of lidocaine-H on IS rats.Conclusion Lidocaine exerts neuroprotective effects on IS rats by inhibiting the RhoA/ROCK signaling pathway.