中枢氧化应激对心绞痛模型大鼠心功能的影响

摘要

目的 观察心绞痛大鼠中枢氧化应激水平的变化,并运用NADPH氧化酶抑制剂APO减少超氧化物的生成进而降低中枢氧化应激水平以改善心绞痛时心功能.方法 采用冠脉结扎术制作心绞痛动物模型,假手术组仅进行手术而不造成缺血状态,干预组通过侧脑室插管给予APO (60 μg/3 min),对照组给予人工脑脊液.雄性Sprage-Dawley大鼠随机分为心绞痛干预组(Angina+APO)、心绞痛对照组(Angina +VEH)、假手术干预组(SHAM+APO)和假手术对照组(SHAM+VEH).2 h后各组大鼠分别进行血流动力学、右心室/体重比值、肺/体重比值的测量.免疫组化方法检测下丘脑室旁核NADPH亚基gp91 phox的表达.结果 心绞痛对照组与假手术对照组相比,下丘脑室旁核NADPH亚基gp91 phox表达增加,左心室舒张末压明显升高,左心室内压最大上升速率和最大下降速率明显降低(P<0.05),右心室/体重比值、肺/体重比值均增加(P<0.05).心绞痛干预组与心绞痛对照组相比,中枢NADPH亚基gp91 phox表达减少,右心室/体重比值、肺/体重比值均减小.结论 心绞痛大鼠中枢氧化应激水平升高,降低中枢氧化应激可在一定程度上改善心绞痛大鼠心功能.%Objective To investigate the effect of brain oxidative stress on heart function of angina.Methods Angina or sham surgery (SHAM) in adult male Sprage-Dawley rats were reduced by left anterior descending coronary artery ligation.Intracerebroventricular (ICV) cannulae was implanted and treated with APO (60 μg/3 min).NADPH oxidase inhibitor,or vehicle (VEH) was used for 10 minutes.At the end of the study,left ventricular (LV) function was measured by hemodynamics and rats were sacrificed.Brain tissue and plasma were collected for measurement of the expression of gp91 phox using immunohistochemistry.Heart and lung tissues were also harvested.Body weight (BW),wet lung weight and right ventricular (RV) weight were weighted.Results The expression of gp91phox in the paraventricular nucleus (PVN) of hypothalamus in rats with angina was significantly increased compared with that in sham rats.The expression of gp91phox in the PVN was attenuated by ICV treatment with APO compared with that in angina rats by VEH-treated.ICV treatment with APO also reduced lung/BW radio and RV/BW radio,decreased LV end-diastolic pressure with increased maximum rate of left ventricular pressure rise (+dp/dtmax) and peak rate of left ventricular pressure fall (-dp/dtmax).Conclusion The findings suggested that the brain oxidative stress could increase inhibitor of brain NADPH oxidase to reduce the levels of oxidative stress which might attenuate cardiac dysfunction.