番茄红素对大鼠脑缺血再灌注损伤的影响

Effects of lycopene on cerebral ischemia-reperfusion injury in rats

目的观察番茄红素(LP)对大鼠局灶性脑缺血再灌注损伤(I/R)及机体氧化应激水平影响的作用和机制。方法将大鼠分为5组,正常对照组、模型对照组、假手术组和两个实验组大鼠(分别每天灌胃5或20mg/kg番茄红素),15d后采用大脑中动脉栓塞法(MCAO)制备大鼠局灶性脑缺血/再灌注模型。分别在再灌注后第3h和第24h进行神经行为评分;再灌注24h后处死动物,计算脑梗死体积;测定脑组织一氧化氮(NO)、诱导型一氧化氮合酶(iNOS)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、丙二醛(MDA)及血清尿酸(UA)的含量及活性,并采用RT-PCR法检测脑皮质组织中低氧诱导因子(HIF)-1α mRNA、Bcl-2 mRNA的表达水平。结果与模型组比较,番茄红素组大鼠的脑梗死体积较小,神经症状较轻,脑组织SOD、CAT活性较高,iNOS活性及MDA、NO、血清UA的含量较低;与正常对照组相比,LP高剂量组HIF-1α mRNA表达上调;而Bcl-2 mRNA表达上调仅在LP低剂量组较为明显。结论番茄红素对大鼠的局灶性脑I/R损伤具有一定的保护作用,其机制可能与提高抗氧化酶活性,抑制脂质过氧化反应,降低iNOS活性,上调脑组织HIF-1α和Bcl-2水平有关。

Objective To study the protective effects of lycopene （LP） on cerebral ischemia-reperfusion injury and oxidative stress in SD rats and the mechanism of them. Methods The rats were divided into five groups： normal control group,model control group,sham group and two LP groups （fed with 5mg /kg bw or 20mg /kg bw of lycopene daily for 15 days）. The model for cerebral ischemia-reperfusion injury was established by middle cerebral artery occlusion （MCAO）. The score of neurological behavior was evaluated at the 3rd and 24th hours after reperfusion. The rats were put to death 24h after reperfusion. The size of cerebral infarction was measured. The activities of iNOS,SOD,CAT and the contents of NO and MDA in brain and serum uric acid were measured. The expressions of Bcl-2 mRNA and HIF-1αmRNA in cortex were examined by using reverse transcription polymerase chain reaction （RT-PCR） technique. Results In comparison with the model group,the neurological deficits were milder,the volumes of cerebral infarction were smaller,the activities of SOD,CAT in brain tissue were higher,the activities of iNOS as well as the contents of NO,MDA in brain tissue and serum uric acid were lower in Lycopene groups. Compared with the model group and control group,the expression of HIF-1α mRNA of cortex in the high dose lycopene （20mg /kg bw） group was up-regulated; while the expression of Bcl-2 mRNA of cortex was up-regulated only in the low dose lycopene （ 5mg /kg bw） group. Conclusion There were some protective effects of oral administration of lycopene against cerebral ischemia-reperfusion injuries induced by focal cerebral ischemia and oxidative stress. The possible mechanism may be related with increasing activities of antioxidant enzymes,inhibiting lipid peroxidation,decreasing activities of iNOS,and up-regulating the expression of HIF-1α mRNA as well as Bcl-2 mRNA.