亚低温联合氯丙嗪对脑缺血再灌注损伤大鼠氧化应激反应的影响

Effects of Mild Hypothermia Combined with Chlorpromazine on Oxidative Stress in Rats with Cerebral Ischemia-reperfusion Injury

目的探讨亚低温联合氯丙嗪对脑缺血再灌注损伤(CIRI)大鼠氧化应激反应的影响。方法将75只SD大鼠随机分为假手术组、CIRI组、亚低温组、氯丙嗪组和亚低温联合氯丙嗪组,每组15只。采用神经功能损伤评分(NDS)评价神经功能,酶联免疫吸附法测定神经元特异性烯醇酶(NSE)和S-100β蛋白表达,化学比色法检测超氧化物歧化酶(SOD),硫代巴比妥酸比色法检测丙二醛(MDA),Western Blotting检测NF-E2相关因子2(Nrf2)、血红素加氧酶(HO-1)蛋白表达。结果亚低温组、氯丙嗪组和亚低温联合氯丙嗪组NDS评分和NSE、S-100β、MDA水平均低于CIRI组(P<0.05或P<0.01),SOD、Nrf2和HO-1水平均高于CIRI组(P<0.05或P<0.01)。亚低温联合氯丙嗪组NDS评分及NSE、S-100β、MDA水平均低于亚低温组和氯丙嗪组(P<0.05),SOD、Nrf2和HO-1水平均高于亚低温组和氯丙嗪组(P<0.05或P<0.01)。结论亚低温联合氯丙嗪上调Nrf2/HO-1通路发挥抗氧化作用,进而对脑缺血再灌注大鼠起到神经保护作用。

Objective To observe the effects of mild hypothermia combined with chlorpromazine on oxidative stress in rats with cerebral ischemia-reperfusion injury(CIRI).Methods Seventy-five SD rats were devided into sham group,CIRI group,mild hypothermia group,chlorpromazine group,mild hypothermia combined with chlorpromazine group.Neurological function was evaluated by neurological impairment score(NDS),the expressions of neuron specific enolase(NSE)and S-100βwere detected by enzyme-linked immunosorbent assay(ELISA),superoxide dismutase(SOD)was detected by chemical colorimetry,malondialdehyde(MDA)was detected by glucosinolates barbituric acid colorimetry.The expressions of factor NF-E2 related factor 2(Nrf2),heme oxygenase(HO-1)protein were detected by Western Blotting.Results NDS scores,NSE,S-100β,and MDA in mild hypothermia group,chlorpromazine group,and mild hypothermia combined with chlorpromazine group were lower than those in CIRI group(P<0.05 or P<0.01),and the expressions of SOD,Nrf2,and HO-1 in mild hypothermia group,chlorpromazine group,and mild hypothermia combined with chlorpromazine group were higher than those in CIRI group(P<0.05 or P<0.01).NDS scores,NSE,S-100β,and MDA in mild hypothermia combined with chlorpromazine group were lower than those in mild hypothermia group and chlorpromazine group(P<0.05),and the expressions of SOD,Nrf2,and HO-1 in mild hypothermia combined with chlorpromazine group were higher than those in mild hypothermia group and chlorpromazine group alone(P<0.05 or P<0.01).Conclusion Mild hypothermia combined with chlorpromazine could up-regulate Nrf2/HO-1 pathway to play an antioxidant role and play a neuroprotective role in rats with CIRI.