补充17β-雌二醇对卵巢切除大鼠心脏中二肽基肽酶3和血红素加氧酶1表达的影响

Effect of 17β-estradiol supplement on the expression of dipeptidyl peptidase 3 and heme oxygenase 1 in cardiac tissues of ovariectomized rats

目的观察二肽基肽酶3(DPP3)和血红素加氧酶1(HO-1)在卵巢切除(OVX)大鼠心脏中的表达变化,探索DPP3在17β-雌二醇(E2)改善OVX大鼠心脏氧化应激的作用。方法以OVX手术绝经大鼠为实验动物模型,补充E2治疗4周为主要干预。根据有无OVX和补充E2将大鼠随机分为4组,分别被命名为假手术对照组(Sham)+溶剂(Veh)组、Sham+E2组、OVX+Veh组和OVX+E2组,每组5只大鼠。检测各组大鼠的心脏质量与体重之比、平均动脉压、心率、左心室压力上升最大速率(dp/dt_(max))和左心室压力下降最大速率(-dp/dt_(max)),采用ELISA检测心脏组织中氧化应激水平,采用蛋白质印迹法检测DPP3和HO-1蛋白表达水平。结果与Sham+Veh组比较,OVX+Veh组大鼠的心脏质量与体重之比增高(P<0.05),平均动脉压升高(P<0.05),心率加快(P<0.05),dp/dt_(max)绝对值和-dp/dt_(max)绝对值均降低(P均<0.05);而E2补充治疗后OVX+E2组大鼠的心脏质量与体重之比下降,平均动脉压和心率均下降,dp/dt_(max)绝对值和-dp/dt_(max)绝对值均增加,与OVX+Veh组相比差异均有统计学意义(P均<0.05)。与Sham+Veh组相比,OVX+Veh组大鼠心脏组织中抗氧化酶过氧化氢酶和超氧化物歧化酶的活性均降低(P均<0.05),活性氧和丙二醛水平均增加(P均<0.05),DPP3和HO-1的蛋白表达水平均降低(P均<0.05);而E2补充治疗4周后OVX诱导的这些效应均改善(P均<0.05)。结论DPP3和HO-1在OVX大鼠心脏组织中表达减少,而E2补充治疗可增加OVX大鼠心脏组织中DPP3和HO-1的表达,并能发挥心脏保护效应。

Objective To observe the expression of dipeptidyl peptidase 3(DPP3)and heme oxygenase 1(HO-1)in cardiac tissues of ovariectomzied(OVX)rats,and to explore the role of DPP3 in 17β-estradiol(E2)-improving stress.Methods OVX operated postmenopausal rats were used as experimental animal models,supplemented with E2 for 4 weeks as the main intervention.The rats were randomly divided into 4 groups according to the presence or absence of OVX and supplementary E2.They were named sham operation control group(Sham)+Vehicle(Veh)group,Sham+E2 group,OVX+Veh group and OVX+E2 group,with 5 rats in each group.The ratio of heart weight to body weight,mean arterial pressure(MAP),heart rate(HR),maximum rate of rise of left ventricular pressure(dp/dt_(max)),and the maximum rate of drop of left ventricular pressure(-dp/dt_(max))of each group were measured.The levels of oxidative stress in cardiac tissues were detected by enzyme-linked immunosorbent assay(ELISA),and the expression levels of DPP3 and HO-1 were detected by Western blotting.Results Compared with the Sham+Veh group,the ratio of heart weight to body weight,MAP and HR were significantly increased,and the absolute values of maximum rate of rise of left ventricular pressure dp/dt_(max) and-dp/dt_(max) were significantly decreased in the OVX+Veh group(all P<0.05);after E2 supplementary treatment,the ratio of heart weight to body weight,MAP and HR were significantly decreased,and the absolute values of dp/dt_(max) and-dp/dt_(max) were significantly increased in the OVX+E2 group than in the OVX+Veh group(all P<0.05).Compared with the Sham+Veh group,the activities of antioxidant enzymes(catalase and superoxide dismutase)and the expression levels of DPP3 and HO-1 were significantly decreased,and the levels of reactive oxygen species and malondialdehyde were significantly increased in the OVX+Veh group(all P<0.05);after 4 weeks of E2 supplement,the effects induced by OVX were improved(all P<0.05).Conclusion The expression of DPP3 and HO-1 is decreased in cardiac tissues of OVX rats,and can be increased by E2 supplement,showing a cardioprotective effect.