α-硫辛酸对大鼠脑缺血再灌注损伤炎性机制的影响

The effect of alpha-lipoic acid on the inflammation of rats cerebral ischemia-reperfution injury as well as expression of inflammatory factor

目的探讨α-硫辛酸对大鼠脑缺血再灌注损伤炎性反应机制的影响。方法将SD大鼠随机分为假手术组(A)、脑缺血再灌注组(B)和硫辛酸预干预组(C),应用线栓法制备大脑中动脉闭塞2 h后再灌注模型,分别于再灌注6 h、24 h、3 d、7 d采用2,3,5-氯化三苯基四氮唑(TTC)染色法检测脑梗死灶大小,采用免疫组织化学和原位杂交的方法检测大鼠核转录因子(nuclear factor kappa B,NF-κB)、肿瘤坏死因子α(tumor necrosis factorα,TNF-α)的表达。结果与假手术组比较,模型组NF-κB的表达于再灌注6 h即增高(P<0.05),TNF-α的表达于24 h增高(P<0.05),3 d时均达高峰(均P<0.05),7 d时仍高于假手术组(均P<0.05);与模型组比较,硫辛酸预干预组于脑缺血再灌注24 h、3 d、7 d时NF-κB和TNF-α表达降低;α-硫辛酸预干预组NF-κB各时点组内比较未见统计学差异(F=2.245,P>0.05)。与模型组比较,α-硫辛酸预干预组梗死体积明显减小,神经功能缺损评分降低(P<0.05)。结论α-硫辛酸对大鼠脑缺血再灌注损伤具有一定的保护作用,其机制可能是α-硫辛酸抑制NF-κB、TNF-α的表达,从而抑制大鼠脑缺血再灌注损伤后的炎症反应有关。

Objective To explore the effect of alpha-lipoic acid on the inflammation of rats cerebral ischemia-reperfution injury. Methods The male Sprague-Dawley（ SD） rats were randomly assigned to sham-opration group,a cerebral ischemia-reperfution group and a alpha-lipoic acid pretreatment ischemia-reperfution group. A model of middle cerebral artery（ MCA） occlusion for 2 h followed by reperfution was induced in rats using sutures method. The infarct volume was determined by 2,3,5-triphenyltetrazolium chloride（ TTC） staining respectively at 6 h,24 h,3 d,7 d after reperfution. Technology of immunohistochemistry and in-situ hybridization were used te detect the expression of NF-κB,TNF-α. Results Compared with the control group,NF-κBlevel of ischemia /reperfution（ I /R） group in ischemia tiusse increased at 6 h after reperfution（ P 0. 05） and TNF-α overexpressed at 24 h（ P〈 0. 05）. They all reached the peak at 3 d. At 7 d,it was still higher than that of the sham-opration roup. Compared with the ischemia /reperfution（ I /R） group,TNF-α decreased in the alpha-lipoic acid pretreatment group since 24 h and they all low expressed at 3 d（ both P 〈0. 05）. NF-κB had no significant difference in comparsion within the alpha-lipoic acid pretreatment group.（ F = 2. 245,P 〉0. 05） Compared with I /R group,the infarct volume was decreased and the neurological function scale was decreased too in the alpha-lipoic acid pretreatment group at difference time points. Conclusions NF-κB,TNF-α are associated with the ischemia-reperfution injury,alphalipoic acid can decrease their expression and inhibit the inflammatory response. Alpha-lipoic acid can decrease infarct volume and improve neurological function.