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目的研究胱硫醚β-合酶(CBS)／硫化氢(H2S)体系和血红素氧合酶-1(HO-1)／一氧化碳 (CO)体系在大鼠脑缺血再灌注损伤中的作用。方法 30只Wistar大鼠随机分为5组(n=6):对照组(C组)、脑缺血再灌注组(I/R组)、脑缺血再灌注+锌原卟啉(HO-1抑制剂)组(I／R+Z组)、脑缺血再灌注+羟氨(CBS抑制剂)组(I／R+H组)、脑缺血再灌注+锌原卟啉十羟氨组(I／R+Z+H组)。采用四血管阻断法建立全脑缺血再灌注损伤模型,I／R+Z组、L／R+H组和I／R+Z+H组夹闭两侧颈总动脉前30 min分别腹腔注射锌原卟啉45 μmol／kg、羟氨5 mmol／L、羟氨5 mmol／L+锌原卟啉45 μmol／kg 1 ml,C、I／R组给予等量生理盐水。再灌注6 h时处死大鼠,取海马,测定海马组织H2S、CO、还原型谷胱甘肽(GSH)、丙二醛(MDA)、超氧化物歧化酶(SOD)水平及CBS mRNA和HO-1 mRNA的表达;电镜下观察海马线粒体变性情况。结果与C组比较,I／R组海马组织CO、H2S、CBS mRNA和HO-1 mRNA、MDA 水平及线粒体变性率均升高,海马组织SOD、GSH水平降低(P<0．01);与I／R组比较,I／R+Z组海马组织CO、HO-1 mRNA水平降低,海马组织H2S、CBS mRNA、GSH、MDA水平升高,I／R+H组海马组织 c0、HO-1 mRNA、MDA水平升高,H2S、CBS mRNA、GSH水平降低;I／R+Z+H组海马组织CO、H2S、 HO-1 mRNA和CBSmRNA、SOD、GSH水平降低,线粒体变性率升高(P<0．05)。结论 CBS／H2Sz系和 HO-1／CO体系可拮抗大鼠脑缺血再灌注损伤,其作用可相互代偿。
Objective To investigate the effects of CBS / H2S and HO-1 / CO on focal cerebral ischemia-reperfusion injury in rats . Methods Thirty Wistar rats were randomly divided into five groups (n = 6): control group (C group), cerebral ischemia reperfusion group (I / R group), cerebral ischemia reperfusion + 1 inhibitor) group (I / R + Z group), cerebral ischemia-reperfusion + hydroxylamine (CBS inhibitor) group (I / R + H group), cerebral ischemia-reperfusion + zinc protoporphyrin, Group (I / R + Z + H group). The model of global cerebral ischemia-reperfusion injury was established by four-vessel occlusion. The rats in I / R + Z, L / R + H and I / R + Injection of zinc protoporphyrin 45 μmol / kg, hydroxylamine 5 mmol / L, hydroxylamine 5 mmol / L + zinc protoporphyrin 45 μmol / kg 1 ml, C, I / R group given the same amount of saline. At 6 h after reperfusion, the rats were sacrificed and the hippocampus was taken for measurement of the levels of H2S, CO, GSH, MDA and SOD in the hippocampus and the levels of CBS mRNA and HO -1 mRNA expression in hippocampus mitochondria were observed under electron microscope. Results Compared with group C, the levels of CO, H2S and CBS mRNA, HO-1 mRNA, MDA and mitochondrial degeneration were significantly increased in hippocampus of I / R group and the levels of SOD and GSH in hippocampus were decreased (P <0.01) Compared with I / R group, the level of CO, HO-1 mRNA in hippocampus and the levels of H2S, CBS mRNA, GSH and MDA in hippocampus of I / R + The levels of mRNA and protein of MDA, SOD and GSH in hippocampus of I / R + Z + H group were significantly lower than those in I / R + Z + H group <0.05). Conclusion The CBS / H2Sz and HO-1 / CO systems can antagonize the cerebral ischemia-reperfusion injury in rats, and their effects can be mutually compensated.