己酮可可碱对压力负荷心衰大鼠心肌细胞凋亡及炎症因子的影响
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摘要
目的:研究及探讨己酮可可碱(pentoxifylline, PTX)对压力负荷心衰大鼠心肌细胞凋亡及炎症因子的影响。方法:采用腹主动脉缩窄的方法制备压力负荷心衰大鼠模型。雄性SD大鼠35只,随机分为5组,分别为假手术组,模型组,氨茶碱组,PTX-L组,PTX-H组。每只大鼠分别在术后第4周、术后8周给予超声心动图检查,测量LVIDd、LVIDs、LVPWd、ISVd、FS、EF;术后第8周处死大鼠,测量大鼠心脏重量指数(HW/BW)和左心室重量指数(LVW/BW,即LVI);左心室组织切片HE染色了解心肌肥厚情况及心肌间质炎症细胞浸润情况;TUNEL法检测左心室心肌细胞凋亡,采用免疫组化及Western blot法检测心肌组织细胞因子分泌并半定量分析。结果:1.第4周时,模型组、氨茶碱组、PTX-L组、PTX-H组LVPWd与假手术组相比均显著增加(P<0.05)。第8周时,模型组、氨茶碱组FS较其4周时明显下降(P<0.05),且模型组、氨茶碱组、PTX-L组、PTX-H组FS均较假手术组明显下降(P<0.05);PTX-L组、PTX-H组EF较模型组、氨茶碱组显著增高(P<0.05),模型组与氨茶碱之间无显著差别,且模型组及氨茶碱组EF较假手术组显著下降(P<0.05);模型组、氨茶碱组、PTX-L组、PTX-H组LVPWd与假手术组相比均显著增加(P<0.05),LVPWd在模型组、氨茶碱组较PTX-L组、PTX-H组增加更明显(P<0.05),PTX-L组及PTX-H组EF较其第4周时无明显变化,PTX-L组、PTX-H组之间无明显差别,模型组、氨茶碱组之间无明显差别;LVIDd、LVIDs、ISVd在各组间及不同时间点间无明显差别。2.HE染色:PTX-L组、PTX-H组可见到心肌细胞变性、坏死,心肌细胞肥大,排列紊乱;心肌组织炎性细胞浸润,但程度介于模型组、氨茶碱组和假手术组之间。3.TUNEL检测:PTX-L组、PTX-H组凋亡指数较模型组、氨茶碱组显著减少(P<0.05);PTX-L组与PTX-H组组间无差别。4.免疫组化及Western blot检测:PTX-L组、PTX-H组心肌组织中的TNF-α、IL-6的表达较模型组、氨茶碱组显著减少(P<0.05);而PTX-L组、PTX-H组心肌组织中的IL-10的表达较模型组、氨茶碱组显著增加(P<0.05);PTX-L组与PTX-H组组间无差别。结论:PTX能够调节心衰大鼠心肌组织中炎性细胞因子的表达,抑制心肌细胞凋亡,延缓心室重构,改善心功能。
Objective: To investigate the effects of pentoxifylline on apoptosis of myocardial cell and inflammatory factors in heart failure rats triggered by pressure overload
Methods: Pressure overload induced by abdominal aortic banding. Thirty-five male SD rats were subjected to five groups at random: sham-operation group, model group, aminophylline group, pentoxifylline-low group, pentoxifylline-high group. The left ventricular and function indexes of five groups were observed by high-frequency echocardiography on the fourth and the eighth week. Then, in the eighth week, we calculated the heart weight indexes and left ventricular weight indexes of rats, observed the change of the myocardium histomorphology, and detected apoptotic cardiomyocyte using the terminal deoxynucleotidy1 transferase mediated Dutp nick end labeling method(TUNEL). The expression of inflammatory cytokine from myocardium were detected respectively by biochemical methods, and immunohistochemistry and Western blot.
Results: 1. the left ventricle posterior wall thickness (LVPWd) of model group, aminophylline group, pentoxifylline-low group and pentoxifylline-high group in the fourth and eighth week were significantly higher than that of ham operation group (P<0.05). In the eighth week, the percent fraction shortening (FS) of model group and aminophylline group were significantly lower than before (P<0.05). And the percent fraction shortening (FS) of model group, aminophylline group, pentoxifylline-low group and pentoxifylline-high group were significantly lower than that of ham operation group (P<0.05). In the eighth week, percent ejection fraction (EF) of pentoxifylline-low group and pentoxifylline-high group were significantly higher than that of model group and aminophylline group (P<0.05), though those of model group and aminophylline group were similar, and the EF of model group and aminophylline group were significantly lower than that of ham operation group (P<0.05). The LVPWd of pentoxifylline-low group and pentoxifylline-high group were significantly lower than that of model group and aminophylline group (P<0.05). In the eighth week, the EF of pentoxifylline-low group and pentoxifylline-high group were similar with before, and through those of pentoxifylline-low group and pentoxifylline-high group were similar. The left ventricular end diastolic diameter, left ventricular end systolic diameter, interventricular septal thinckness of the five groups were similar.2.Hematoxylin-eosin staining and Western blot show: cadiocyte degenerated, hypertrophy, focal necrosis, arranged confused and companied with inflammatory cells in pentoxifylline-low group and pentoxifylline-high group. Pathohistology of the two groups lied between model group and ham operation group.3. The detection of TUNEL: Apoptotic indexes of pentoxifylline-low group and pentoxifylline-high group were significantly lower than that of model group and aminophylline group (P<0.05). In those of pentoxifylline-low group and pentoxifylline-high group were similar. 4. The detection of biochemical methods and immunhistochemistry and Western blot: the expressions of TNF-α, IL-6 in pentoxifylline-low group and pentoxifylline-high group were significantly lower than that of model group and aminophylline group (P<0.05), and the expressions of IL-10 in pentoxifylline-low group and pentoxifylline-high group were significantly higher than that of model group and aminophylline group (P<0.05), In those of pentoxifylline-low group and pentoxifylline-high group were similar.
Conclusion: PTX can regulate the inflammatory cytokine of myocardium, suppress the apoptosis of myocardial cell, postpone the remodeling of ventricular, and improve heart function of heart failure rats.
Objective: To investigate the effects of pentoxifylline on apoptosis of myocardial cell and inflammatory factors in heart failure rats triggered by pressure overload
Methods: Pressure overload induced by abdominal aortic banding. Thirty-five male SD rats were subjected to five groups at random: sham-operation group, model group, aminophylline group, pentoxifylline-low group, pentoxifylline-high group. The left ventricular and function indexes of five groups were observed by high-frequency echocardiography on the fourth and the eighth week. Then, in the eighth week, we calculated the heart weight indexes and left ventricular weight indexes of rats, observed the change of the myocardium histomorphology, and detected apoptotic cardiomyocyte using the terminal deoxynucleotidy1 transferase mediated Dutp nick end labeling method(TUNEL). The expression of inflammatory cytokine from myocardium were detected respectively by biochemical methods, and immunohistochemistry and Western blot.
Results: 1. the left ventricle posterior wall thickness (LVPWd) of model group, aminophylline group, pentoxifylline-low group and pentoxifylline-high group in the fourth and eighth week were significantly higher than that of ham operation group (P<0.05). In the eighth week, the percent fraction shortening (FS) of model group and aminophylline group were significantly lower than before (P<0.05). And the percent fraction shortening (FS) of model group, aminophylline group, pentoxifylline-low group and pentoxifylline-high group were significantly lower than that of ham operation group (P<0.05). In the eighth week, percent ejection fraction (EF) of pentoxifylline-low group and pentoxifylline-high group were significantly higher than that of model group and aminophylline group (P<0.05), though those of model group and aminophylline group were similar, and the EF of model group and aminophylline group were significantly lower than that of ham operation group (P<0.05). The LVPWd of pentoxifylline-low group and pentoxifylline-high group were significantly lower than that of model group and aminophylline group (P<0.05). In the eighth week, the EF of pentoxifylline-low group and pentoxifylline-high group were similar with before, and through those of pentoxifylline-low group and pentoxifylline-high group were similar. The left ventricular end diastolic diameter, left ventricular end systolic diameter, interventricular septal thinckness of the five groups were similar.2.Hematoxylin-eosin staining and Western blot show: cadiocyte degenerated, hypertrophy, focal necrosis, arranged confused and companied with inflammatory cells in pentoxifylline-low group and pentoxifylline-high group. Pathohistology of the two groups lied between model group and ham operation group.3. The detection of TUNEL: Apoptotic indexes of pentoxifylline-low group and pentoxifylline-high group were significantly lower than that of model group and aminophylline group (P<0.05). In those of pentoxifylline-low group and pentoxifylline-high group were similar. 4. The detection of biochemical methods and immunhistochemistry and Western blot: the expressions of TNF-α, IL-6 in pentoxifylline-low group and pentoxifylline-high group were significantly lower than that of model group and aminophylline group (P<0.05), and the expressions of IL-10 in pentoxifylline-low group and pentoxifylline-high group were significantly higher than that of model group and aminophylline group (P<0.05), In those of pentoxifylline-low group and pentoxifylline-high group were similar.
Conclusion: PTX can regulate the inflammatory cytokine of myocardium, suppress the apoptosis of myocardial cell, postpone the remodeling of ventricular, and improve heart function of heart failure rats.
引文
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