3-氨基苯甲酰胺对大鼠心肌梗死后心力衰竭心肌细胞细胞因子、多聚ADP核糖聚合酶和凋亡诱导因子蛋白表达的影响

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目的:研究多聚ADP核糖聚合酶(PARP)阻滞剂3-氨基苯甲酰胺(3-AB)对心力衰竭(HF)大鼠心肌白细胞介素-10(IL-10)、肿瘤坏死因子-α(TNF-α)水平及对PARP和凋亡诱导因子(AIF)蛋白表达的影响。方法:结扎135只成年雄性Wistar大鼠冠状动脉前降支6周制备HF模型,随机分为HF组、3-AB治疗组(3-AB组)和Sham组。治疗组应用3-AB治疗(30 mg/kg)。治疗2、4、6周后采用放射免疫法测定大鼠心肌IL-10、TNF-α水平,采用免疫组化方法检测心肌PARP和AIF蛋白表达变化。结果:IL-10水平变化:与Sham组相比,HF组各时间点明显增高(P<0.05),3-AB组较HF组各相同时间点明显降低(P<0.05);TNF-α水平:HF组各时间点均较Sham组明显增高(P<0.05),而3-AB组较HF组各相同时间点明显降低(P<0.05)。PARP蛋白表达:HF组各时间点均较Sham组增加(P<0.05),3-AB组各时间点均较HF组明显减少(P<0.05)。AIF蛋白表达:HF组各时间点较Sham组增加,3-AB组各时间点较HF组明显减少(P<0.05)。结论:3-AB可抑制IL-10、TNF-α的释放;抑制PARP和AIF蛋白表达,从而抑制炎症反应和细胞凋亡,对HF大鼠心肌细胞发挥保护作用。 AIM: To investigate the effect of 3-aminobenzamide (3-AB), a blocker of poly-ADP ribose polymerase (PARP) inhibitor, on interleukin-10 (IL-10), tumor necrosis factor- α (TNF-α) levels and the expression of PARP and apoptosis-inducing factor (AIF) protein. Methods: HF model was established by ligating 135 adult male Wistar rats for 6 weeks and were randomly divided into HF group, 3-AB group (3-AB group) and Sham group. The treatment group was treated with 3-AB (30 mg / kg). The levels of IL-10 and TNF-α in myocardium were detected by radioimmunoassay after 2, 4 and 6 weeks of treatment. The expressions of PARP and AIF in myocardium were detected by immunohistochemistry. Results: The levels of IL-10 in HF group were significantly higher than those in Sham group at each time point (P <0.05) : Compared with Sham group, the levels of HF in HF group were significantly higher than those in Sham group (P <0.05), while those in HF group were significantly lower than those in HF group (P <0.05). The expression of PARP in HF group was higher than that in Sham group at each time point (P <0.05), but significantly decreased at 3-AB compared with HF group at each time point (P <0.05). The expression of AIF protein in HF group was higher than that in Sham group at each time point, but significantly decreased in HF group at 3-AB group (P <0.05). Conclusion: 3-AB can inhibit the release of IL-10 and TNF-α, inhibit the expression of PARP and AIF protein, thereby inhibiting the inflammatory response and apoptosis and exerting a protective effect on HF rat cardiomyocytes.
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