L-卡尼汀对大鼠脑缺血再灌注性损伤预防和治疗效果的对比研究

The Comparison between Preventive and Therapeutic Effect of L-carnitine on Cerebral-ischemia Reperfusion Injury of Rat

目的本研究采用线栓法复制大鼠局灶性脑缺血再灌注模型,对比观察L-卡尼汀对脑缺血再灌注性损伤的预防作用和治疗效果及其相关机制。方法将84只SD大鼠随机分成Sham组、脑缺血再灌注组(I/R组)、L-卡尼汀预防组(I/R+LCⅠ组)和治疗组(I/R+LCⅡ组),采用改良Longa方法进行大鼠右侧大脑中动脉缺血2h后再灌注,24h后进行神经行为学评分,检测右侧脑梗死体积,测定脑组织ATP含量、血浆和脑组织SOD活性和MDA含量,HE染色检测脑组织形态学变化。结果大鼠经过大脑中动脉缺血2h再灌注24h后,大鼠神经行为学评分显著增加,脑组织的能量ATP减少,血浆和脑组织中的SOD活性降低,MDA的含量升高,与Sham组相比有显著性差异(P<0.05);L-卡尼汀能改善上述各项指标,L-卡尼汀预防组与I/R组相比,上述各指标存在显著性差异(P<0.05),但L-卡尼汀治疗组与I/R组相比,上述各指标的差异无显著性意义(P>0.05);HE染色结果显示L-卡尼汀具有抗凋亡作用。结论 L-卡尼汀通过改善能量代谢、抗氧化、抗凋亡等途径,对大鼠局灶性脑缺血再灌注损伤有预防作用,但治疗效果不显著。

Objective To study the preventive and therapeutic effect of L-carnitine on cerebral ischemia-reperfusion injury and its possible molecular mechanism,by reproduceing the rat model of focal cerebral ischemia-reperfusion. Methods Eighty-four SD rats were randomly divided to Sham group,Ischemia-reperfusion injury（ I/R） group,L-carnitine prevention（ I/R ＋ LC Ⅰ） group and L-carnitine treatment group（ I/R ＋ LCⅡ）. Blood reperfusion was conducted after 2 hours of ischemia of cerebral right middle artery of rats with modified Longa method,and behavioral scores were recorded 24 hours after operation. The volume of right cerebral infarction,the content of ATP,MDA and the activity of SOD in plasma and brain tissue were measured. The morphological changes in the rat brains were tested by HE staining. Results After reperfusion,significant increase of behavioral scores,decrease of ATP content and activity of SOD,increase of MDA content in plasma and brain tissue were found in I/R group as compared to Sham group（ P〈0. 05）. However,L-carnitine prevention can reverse the effect of reperfusion injury. Significant differences were found between I/R ＋ LC Ⅰgroup and I/R group（ P〈0. 05）. In addition,no significant difference was detected between I/R ＋ LCⅡ group and I/R group（ P〈0. 05）; HE staining indicated that the L-carnitine prevention had the anti-apoptotic effect against reperfusion injury in neurons. Conclusion L-carnitine has preventive effect against focal cerebral ischemia-reperfusion injury in rats by promoting level of energy metabolism,lowering oxidative stress and apoptosis in neurons,but has no obviously therapeutic effect.