【摘要】 目的:研究过氧化酶体增殖物激活受体γ(PPARγ)配体罗格列酮能否逆转心力衰竭大鼠心脏间质纤维化。方法:60只雄性Wistar大鼠分3组:(1)心力衰竭模型组(CHF,n=25),阿霉素2.5mg/kg,尾静脉注射,每周1次,连续10周;(2)心力衰竭模型+罗格列酮治疗组(ROS,n=25),ROS3mg.kg-1.d-1,灌胃治疗;(3)正常对照组(CON,n=10)。于实验第12周,进行超声检测评价其心功能,用放免法检测血浆TNF-α、血管紧张素-II(Ang-Ⅱ)及醛固酮(Ald)水平,氯胺T法检测羟脯氨酸及胶原含量,苦味酸天狼星红染色进行左室胶原特异染色及定量分析,计算胶原容积分数(CVF),并作HE染色观察其组织学变化。结果:ROS组较CHF组死亡率明显降低(20%vs40%,P<0.01)。与CON组相比,CHF组血浆TNF-α、Ang-Ⅱ及Ald水平升高(P<0.01),而ROS治疗组较CHF组降低(P<0.01)。CHF组羟脯氨酸及胶原含量增加(P<0.01),经ROS治疗后有所减低。苦味酸天狼星红染色显示CHF组左室胶原明显增加,CVF明显增高(P<0.01);而ROS组则纤维化明显减轻,CVF降低(P<0.01)。病理学结果证实CHF组符合心肌病样改变,而ROS组可逆转这种改变。结论:PPARγ配体罗格列酮通过抑制TNF-α、Ang-Ⅱ及Ald等,部分逆转心力衰竭大鼠心脏间质纤维化。更多还原

【Abstract】 AIM:To investigate whether the ligand of peroxisome Proliferator-activated receptor γ(PPARγ),rosiglitazone(ROS),can reverse myocardial interstitial fibrosis in rats with heart failure.METHODS:Sixty weight-matched adult male Wistar rats were randomly divided into 3 groups as follows:(1)the CHF group,in which 2.5 mg/kg of adriamycin(ADR) was weekly injected via a tail vein for 10 weeks(n=25);(2)the ROS group,concomitant ROS and ADR,in which ROS as a PPARγ ligand was administered by daily gavage at a dose of 3 mg·kg-1·d-1(n=25);(3)the control group(n=10).The cardiac function was evaluated by echocardiographic method.The plasma concentrations of TNF-α,Angiotensin II(Ang II) and Aldsterone(Ald) were determined by immunoradiometric assay at 12 weeks after treatment.The hydroxyproline and collagen content were determined by the methods of Chloramines T and Picric acid-Sirius red staining techniques.The pathological change was analyzed by histological hematoxylin-eosin staining.RESULTS:The mortality of ROS-treated rats was significantly lower than that of CHF group(20% versus 40%,P<0.01).The plasma concentrations of TNF-α,Ang II and Ald were higher in the CHF group than those in the control group(P<0.01),which was decreased by ROS treatment.The hydroxyproline and collagen content were increased in CHF group(both P<0.01),but decreased in ROS group.The myocardial collagen of left ventricle increased and the collagen volume fraction(CVF) increased significantly,which were partly reversed by ROS treatment(P<0.01).The pathological results showed there was changes of cardiomyopathy in CHF group,ROS reversed the pathological changes of left ventricular myocardium of CHF.CONCLUSION:Pretreatment with PPARγ ligand ROS could partly reverse myocardial interstitial fibrosis in rats with heart failure by downregulating the expression of TNF-α,Ang II and Ald.更多还原