杜仲提取物预处理对脑缺血再灌注损伤大鼠抗氧化能力及一氧化氮的影响

Effects of Eucommia ulmoides extracts on antioxidant capacity and nitric oxide after focal brain ischemia reperfusion injury in rats

目的观察杜仲提取物预处理对大鼠脑缺血再灌注损伤中抗氧化能力及一氧化氮的影响,探讨杜仲提取物抗脑缺血再灌注损伤的作用机制。方法雄性SD大鼠120只,随机分为假手术组、模型组、尼莫地平预处理(12 mg·kg^(-1))组和杜仲提取物不同剂量预处理(分别给予200、400、800 mg·kg^(-1)·d^(-1))组,均n=20。各给药组均在制模前预先灌胃给药14 d,采用线栓法制备大鼠局灶性脑缺血再灌注损伤模型,假手术组只分离血管,不留置线栓,假手术及模型组分别给予同体积蒸馏水。缺血2 h再灌注24 h后,用2,3,5-氯化三苯基四氮唑(TTC)染色测定梗死面积,HE染色观察病理形态改变,检测血清及脑组织中丙二醛(MDA)、超氧化物歧化酶(SOD)、一氧化氮(NO)含量及诱导型一氧化氮合酶(iNOS)活性。结果与模型组相比,杜仲提取物各剂量组大鼠脑梗死面积减少(P<0.05)。杜仲提取物中、高剂量组血清和脑组织中的MDA和NO含量及iNOS活性均显著降低,SOD活性显著升高(P<0.05),与尼莫地平组相比无显著差异(P>0.05)。结论杜仲提取物预处理减轻脑缺血再灌注损伤的机制可能是提高抗氧化能力并降低NO水平。

AIM To investigate the effects of Eucommia Ulmoides extracts on antioxidant capacity and nitric oxide of cerebral ischemia-reperfusion in rats, and to explore the protective mechanisms. METHODS One hundred and twenty Sprague-Dawley rats were randomly divided into sham group, model group, nimodipine （ 12 mg·kg^-1·d^-1） and Eucommia ulmoides extracts （200, 400, 800mg·kg^-1·d^-1） preconditioning groups. Each group had 20 animals. All rats were administrated for 14 days pretreatment by gavages. The cerebral isehemia reperfusion model was built through thread block. The middle cerebral artery in rats was occluded for 2 h by an intraluminal filament and then reperfused to cause transient focal cerebral ischemia. Twenty-four hours after reperfusion, the infarction area was shown with 2, 3, 5-triphenyl tetrazolium chloride （TFC） staining. Malondi-aldehyde （MDA） content and superoxide dismutase （SOD） activity of plasma and brain were observed. The contents nitric oxide （NO） and the activities of inducible nitric oxide synthase （iNOS） were also investigated. RESULTS Compared with the model group, the infarction area of all Eucommia ulmoides extracts preconditioning groups were significantly lower （P 〈 0.05）, and pathological change was lighter significantly. MDA and NO contents and iNOS activities of serum and brain tissue in the Eucommia ulmoides extracts 400 and 800mg·kg^-1·d^-1 groups decreased and SOD activities increased significantly （P 〈 0.05）.CONCLUSION Eucommia ulmoides extracts improving antioxidant capacity have protective effects on focal brain ischemia reperfusion injury in rats by and depressing NO level.