VEGF通过TWIK钾通道对缺血性脑卒中患者的脑保护作用

Study of the cerebral protective effect of VEGF on ischemic stroke through TWIK potassium channel

目的探讨VEGF对缺血性脑卒中的影响,并探讨钾离子通道的相关作用机制。方法选取2020年4月至2022年1月于海口市人民医院神经内科就诊的100例缺血性脑卒中患者作为研究对象,将其根据脑卒中临床神经功能缺损程度评分量表(China Stroke Scale,CSS)评分分为预后较好组和预后不良组,检测各组血清VEGF表达,分析影响脑梗死预后不良的因素。获取大鼠脑皮质神经元细胞,将其分为空白对照组、缺氧组、低剂量VEGF组、中剂量VEGF组、高剂量VEGF组、抑制剂组。检测各组细胞凋亡率以及各组细胞凋亡蛋白表达。结果患者血清VEGF水平随着时间呈递增趋势,在第2、7天出现峰值,第14天下降;与预后较好组比较,预后不良组患者年龄较高,高血压、糖尿病、房颤史者较多,入院NIHSS评分较高,VEGF水平较低(P<0.05);年龄、高血压、糖尿病、房颤史、入院NIHSS评分、VEGF水平均为影响患者预后的危险因素(P<0.05)与空白对照组相比较,缺氧组凋亡率较高;与缺氧组比较,低、中、高剂量VEGF组、抑制剂组凋亡率较低(P<0.05);且低剂量VEGF组和抑制机组抑制作用最显著,两组比较差异无统计学意义(P>0.05);与空白对照组比较,缺氧组Bcl-2蛋白表达较低,Bax、TREK蛋白表达较高,与缺氧组比较,低、中、高剂量VEGF组、抑制剂组Bcl-2、Bax、TREK蛋白表达均有所改善(P<0.05);中剂量VEGF组和抑制剂组比较差异无统计学意义(P>0.05)。结论VEGF对缺血性脑卒中患者具有脑保护的作用,可能是通过TWIK相关钾通道实现的。

Objective To investigate the effect of VEGF on ischemic stroke and the significance of potassium channels in this mechanism.Methods One hundred ischemic stroke patients who attended our hospital from April 2020 to January 2022 were selected,and were divided into better prognosis group and poor prognosis group according to the clinical neurological deficits in stroke scale(China Stroke Scale,CSS).And serum VEGF expression was detected in each group to analyze the factors affecting poor prognosis of cerebral infarction.Rat brain cortical neuronal cells were obtained and divided into blank control group,hypoxic group,low-dose VEGF group,medium-dose VEGF group,high-dose VEGF group and inhibitor group.The apoptosis rate of each group and the expression of apoptosis protein in each group were detected.Results Patients′serum VEGF levels showed an increasing trend over time,with a peak on Day 7 and decrease on Day 14.Compared with the better prognosis group,patients in the poor prognosis group were significantly older,with significantly higher proportions of hypertension,diabetes,history of atrial fibrillation,had significantly higher admission NIHSS scores,and significantly lower VEGF levels(P<0.05).Age,hypertension,diabetes,a history of atrial fibrillation,admission NIHSS scores,and VEGF levels were all risk factors affecting patients′prognosis(P<0.05).Compared with the blank control group,the apoptosis rate was significantly higher in the hypoxic group;compared with the hypoxic group,the apoptosis rate was significantly lower in the low,medium and high dose VEGF group and the inhibitor group(P<0.05).And the inhibition effect was most significant in the low dose VEGF group and the inhibitor group(P<0.05),while the difference between the two groups was not statistically significant(P>0.05).Compared with the blank control group,the hypoxic group Bcl-2 protein expression was significantly lower and Bax and TREK protein expression were significantly higher in the hypoxic group;and Bcl-2,Bax and TREK protein expression were significantly improved in the low,medium and high dose VEGF group and inhibitor group compared with the hypoxic group(P<0.05),while the difference between the medium dose VEGF group and inhibitor group was not statistically significant(P>0.05).Conclusion VEGF has a cerebral protective effect in patients with ischemic stroke,possibly through TWIK-related potassium channels.