L-精氨酸通过抑制NF-кB途径减轻大鼠脑缺血-再灌注损伤

L-arginine improve the ischemic injury via inhibiting the activity of NF-кB in brain of ischemia-reperfusion rat

目的观察L-精氨酸(L-Arg)对大鼠脑缺血-再灌注(I/R)损伤的作用并探讨其机制。方法成年健康SD大鼠36只随机分3组,假手术(Sham)组、I/R组、L-Arg治疗(ARG)组,每组12只,采用大脑中动脉阻塞(MCAO)法建立大鼠局灶脑缺血模型。I/R组、ARG组于缺血2 h再灌注时分别给予生理盐水和L-Arg,实验中监测大鼠血压。于再灌注72 h后进行神经功能评分,TTC染色检测各组脑梗死体积百分比,Western blot测定大鼠缺血脑组织内NF-κB p65、IκBα的表达水平并进行组间比较。结果 1各组大鼠血压比较,差异无统计学意义(P>0.05);2与I/R组相比较,I/R后72 h,ARG组神经功能缺损程度评分明显改善(P<0.05),脑梗死体积显著缩小(P<0.05);3与Sham组比较,I/R组NF-κB p65表达明显升高(P<0.01),IκBα蛋白的表达明显降低(P<0.01);ARG组NF-κB p65的表达水平显著低于I/R组、高于Sham组(P<0.05),ARG组IκBα的表达水平显著高于I/R组、低于Sham组(P<0.05)。结论 I/R后早期给予L-Arg可减轻脑组织损伤,其机制与一氧化氮(NO)抑制NF-кB激活有关。

Objective To observe the effect of L-arginine( L-Arg) on brain injury of ischemia-reperfusion rat and explore the possible mechanism.Methods The rat model of middle cerebral artery occlusion( MACO) was established. 36 Sprague-Dawley( SD) rats were randomly divided into sham group( n = 12),ischemia-reperfusion( I/R) group( n= 12) and L-arginine( ARG) group( n= 12). At 2h after I/R,normal saline and L-Arg were administered to the I / R and ARG groups respectively by intraperitoneal injection. At 72 h after reperfusion,the neurologic function impairment was evaluated by longa standard,brain was stained with 2% triphenyltetrazolium chloride( TTC) for assessment of the volume of infarction,NF-κB p65 and IκBα protein levels were examined by Western blot technique. Results 1 There were no significant difference among 3 groups( P>0.05); 2 Compared with I / R group,treatment with L-Arg could significantly improve neurologic function( P<0.05),and the infarct volume reduced( P<0.05); 3After 72 h of reperfusion,the expression of NF-κB p65 and IκBα protein in I / R group was significantly increased compared with the sham group( P<0.01),and the NF-κB p65 level was lower while the IκBα level was higher in ARG group than that in I / R group( P<0.05). Moreover,there was significant difference between ARG and sham group about NF-κB p65 and IκBα protein expression after 72 h of reperfusion( P<0.05).Conclusion Treat with L-Arg in the early stage could reduce I / R injury of the brain,the protective mechanism may be related to inhibition of NF-κB signaling pathway by L-Arg.