L-卡尼汀预防脑缺血再灌注性损伤的机制研究

The Mechanism of Preventive Effect of L-carnitine on Cerebral-ischemia Reperfusion Injury

目的采用线栓法复制大鼠大脑中动脉阻塞模型,探究L-卡尼汀对脑缺血再灌注性损伤的预防作用的潜在机制。方法将72只SD大鼠随机分成假手术组(Sham组)、脑缺血再灌注组(I/R组)和L-卡尼汀预防组(LC组)。采用改良Longa方法进行大鼠右侧大脑中动脉缺血2h再灌注24h后,ELISA法检测血清及脑组织炎症介质IL-1β及肿瘤坏死因子TNF-α变化,检测大鼠右侧脑梗死体积及脑组织含水量,尼氏染色检测脑组织细胞形态,免疫组化和Western-Blot法分别检测脑组织中Bax、Bcl-2表达量。结果大脑中动脉缺血2h再灌注24h后,脑组织和血清中炎症介质增多,脑梗死体积及脑含水量增加,尼氏染色显示缺血区域细胞排列紊乱,有大量的细胞坏死,免疫组化和Western-Blot结果显示脑组织中Bax含量升高,而Bcl-2降低,与Sham组比较有显著性差异(P<0.05);L-卡尼汀预处理能改善上述各项指标,与I/R组比较,上述各指标存在显著性差异(P均<0.05),免疫组化和Western-Blot结果显示L-卡尼汀具有抗凋亡作用。结论L-卡尼汀通过抗炎和抗凋亡,对局灶性脑缺血再灌注损伤有良好的预防作用。

Objective To study the preventive effect of L-carnitine on cerebral ischemia-reperfusion injury.Methods 72 SD rats were randomly divided into sham,ischemia-reperfusion injury(I/R)and L-carnitine prevention(LC)groups.2h after right middle cerebral artery occlusion via the intraluminal filament technique,the cerebral blood supply was restored for 24h.The volume of infarction and water content in rat brain were measured,the contents of inflammatory factors IL-1βand TNF-αin blood and cerebral tissues were measured by ELISA,and the expression levels of Bax and Bcl-2 were detected by IHC staining and western blotting.Results I/R group showed significant increase in volume of infarction,water content in rat brain,the release of inflammatory factors IL-1βand TNF-αthe expression level of Bax and significant decrease in Bcl-2 level of brain tissue,compared to sham group(P<0.05).Nissl staining showed remarkable neuronal necrosis and irregularly arranged neurons in zone of ischemia.Pretreatment with LC significantly mitigate all above biochemical indicators as compared to I/R group(P<0.05).Conclusion L-carnitine may have preventive effect on rat focal cerebral ischemia-reperfusion injury through anti-inflammatory and anti-apoptotic pathways.