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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。
AIM: To investigate whether Rosiglitazone, a ligand of peroxisome proliferator - activated receptor γ (PPARγ), can reverse cardiac interstitial fibrosis in rats with heart failure. Methods: Sixty male Wistar rats were divided into three groups: (1) heart failure model group (CHF, n = 25), doxorubicin 2.5mg / kg and tail vein injection once a week for 10 weeks; ), Heart failure model + rosiglitazone treatment group (ROS, n = 25), ROS3mg.kg-1.d-1, and intragastric administration; (3) normal control group (CON, n = 10). At the twelfth week of the experiment, the heart function was evaluated by ultrasound, the level of plasma TNF-α, Ang-Ⅱ and Aldosteron were detected by radioimmunoassay, the levels of hydroxyproline and Collagen content and picric acid Sirius red staining were used to perform specific staining and quantitative analysis of left ventricular collagen. The collagen volume fraction (CVF) was calculated and the histological changes were observed by HE staining. Results: The mortality of ROS group was significantly lower than that of CHF group (20% vs 40%, P <0.01). Plasma TNF-α, Ang-Ⅱ and Ald levels increased in CHF group compared with CON group (P <0.01), while decreased in CHF group compared with CHF group (P <0.01). The levels of hydroxyproline and collagen in CHF group increased (P <0.01), and decreased after ROS treatment. The picric acid Sirius red staining showed that left ventricular collagen was significantly increased and CVF was significantly increased in CHF group (P <0.01); while in ROS group, fibrosis was significantly reduced and CVF was decreased (P <0.01). Pathological results confirmed that the CHF group was consistent with changes in cardiomyopathy, whereas ROS group reversed this change. CONCLUSION: Rosiglitazone, a PPARγ ligand, partially reverses cardiac interstitial fibrosis in rats with heart failure by inhibiting TNF-α, Ang-Ⅱ and Ald.