血晶素对间歇性低氧大鼠作用的研究

Study of hemin in intermittent hypoxic rats

目的研究血红素加氧酶-1(HO-1)激动剂血晶素对间歇性低氧大鼠血压的影响,探讨间歇性低氧致动物血压变化的机制和调控方法。方法将24只雄性SD大鼠随机分为血晶素组、间歇低氧组及正常组,每组8例。血晶素组大鼠接受腹腔内注射血晶素30 min后置于常压低氧有机玻璃箱内,使其间歇性低氧8 h/d;间歇低氧组大鼠接受腹腔内注射生理盐水30 min后置于常压低氧有机玻璃箱内,使其间歇性低氧8 h/d,箱体内氧气浓度与血晶素组相同;正常组大鼠接受每天早晨腹腔内注射生理盐水后置于玻璃箱中正常通气。三组大鼠均在同等条件下室温常规饲养。35 d后测定大鼠平均颈总动脉压力(mCAP),检测其血浆一氧化碳(CO)含量,应用逆转录聚合酶链反应检测相关组织器官中HO-1 mRNA的表达,用免疫组织化学检测相关组织器官中HO-1蛋白表达。结果 mCAP在间歇低氧组较血晶素组及正常组明显升高(P<0.05),在血晶素组较正常组高(P<0.05)。血浆CO含量在血晶素组较间歇低氧组、正常组高(P<0.05),间歇低氧组与正常组差异无统计学意义(P>0.05)。肝、脾、肺、肾HO-1 mRNA的表达在血晶素组较间歇低氧组及正常组高(P<0.05),在间歇低氧组较正常组高(P<0.05)。mCAP与HO-1 mRNA呈曲线趋势,二次方曲线拟合方程为Y=39.715+446.640X-334.353X^2。结论间歇性低氧可使大鼠的血压升高,相关组织器官中的HO-1表达增加,但血浆CO含量并不升高。使用血晶素可使间歇性低氧大鼠体内HO-1及CO均升高,并有一定程度的降血压作用。

Objective To study the influence of hemin on blood pressure of intermittent hypoxic rats and investigate the mechanism of hypertension caused by intermittent hypoxia.Methods Twenty-four male SD rats were randomly divided into a hemin group,an intermittent hypoxia group(IH group) and a normal group.Thirty minutes after intraperitoneal injection of hemin,the rats in the hemin group were exposed to intermittent normobaric hypoxic environment(8 h/d).The rats in the IH group were intraperitoneal injected with normal sodium and then exposed to the same environment(8 h/d).The rats in the normal group were intraperitoneal injected with normal sodium and placed in the glass box.The three groups were bred in the same condition.Thirty-five days later,the mean carotid artery pressure(mCAP) of the rats was measured and their plasma carbon monoxide(CO) level was measured by Chalmer’s method.Reverse transcription polymerase chain reaction was performed to detect the levels of heme oxygenase-1(HO-1) mRNA expression in lung,liver,spleen,kidney and other organs.The expression of HO-1 protein in the organs was detected by immunohistochemistry.Results The mCAP in the IH group was significantly higher than the hemin group and the normal group(P<0.05),and was higher in the hemin group than the normal group(P<0.05).The concentration of plasma CO in the hemin group was higher than the IH group and the normal group(P<0.05).There was no significant difference in plasma CO between the IH group and the normal group(P>0.05).The expression of HO-1 mRNA of lung,liver,spleen and kidney in the hemin group and the IH group was higher than the normal group(P<0.05),and was higher in the hemin group than the IH group(P<0.05).The relationship between mCAP and HO-1 mRNA showed a curvilinear trend.The quadratic curve fitting equation was Y=39.715+446.640X-334.353X^2.Conclusions Intermittent hypoxia can cause hypertension in rats.The HO-1 expression is increased in hypoxic rats,but the plasma CO does not increase significantly.As an inducer of HO-1,hemin can increase the expression of HO-1 and CO in hypoxic rats,then lower their blood pressure to some extent.