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目的:探讨Ⅰ型多聚ADP核糖合成酶(PARP1)在心肌梗死后大鼠心肌组织中的表达及活性变化,以及对相关炎性细胞因子[白细胞介素(IL)-6、IL-10、肿瘤坏死因子-α(TNF-α)]和转录因子(NF-κB、AP-1)表达的影响。方法:结扎冠状动脉左前降支(LAD)近端建立急性心肌梗死(AMI)模型,随机分为AMI组、梗死低剂量PARP抑制剂3-氨基苯甲酰胺(3AB)干预(3AB30)组、梗死高剂量干预(3AB100)组和假手术组。3AB30组和3AB100组分别在腹腔注射3-AB30mg/kg和100mg/kg,AMI组和假手术组给予同等体积0.9%氯化钠溶液腹腔注射。测定各组大鼠术后第1、3、7天心脏功能,非梗死区PARP1的蛋白表达及活性与IL-6、IL-10、TNF-浕的表达和转录因子NF-κB和AP-1的活性。结果:心肌梗死后非缺血区PARP1表达在第1天即明显增加,至第7天仍高于假手术组,3AB在非梗死区不仅可以显著抑制TNF-α、IL-6以及PARP1的蛋白表达量和PARP活性,也能够降低NF-κB和AP-1在非梗死区的DNA结合能力。结论:PARP1抑制剂能够明显抑制PARP活性和PARP1表达,在AMI早期通过抑制NF-κB和AP-1活性及炎性因子TNF-α和IL-6表达,能改善心脏功能,减轻心肌损害。
Objective: To investigate the expression and activity changes of type Ⅰ poly (ADP-ribose) synthase (PARP1) in myocardial tissue of rats after myocardial infarction, and to investigate the effect of PARP1 on the expression of inflammatory cytokines [interleukin (IL) -6, IL- Tumor necrosis factor-α (TNF-α)] and transcription factor (NF-κB, AP-1). Methods: Acute myocardial infarction (AMI) model was established at the proximal part of left anterior descending coronary artery (LAD) and was randomly divided into 3 groups: AMI group, 3AB group (3AB30) group, infarct low dose PARP inhibitor High dose intervention (3AB100) group and sham operation group. 3AB30 group and 3AB100 group were intraperitoneally injected with 3-AB30mg / kg and 100mg / kg, AMI group and sham operation group were given the same volume of 0.9% sodium chloride solution intraperitoneal injection. The protein expression and activity of PARP1, the expression of IL-6, IL-10, TNF-浕 and the expressions of NF-κB and AP-1 in cardiac function, Activity. Results: The expression of PARP1 in non-ischemic area increased significantly on the 1st day after myocardial infarction, and still higher than that on the 7th day in the non-ischemic area. 3AB could not only significantly inhibit the protein of TNF-α, IL-6 and PARP1 Expression and PARP activity, but also reduce the DNA binding capacity of NF-κB and AP-1 in non-infarcted area. CONCLUSION: PARP1 inhibitor can significantly inhibit PARP activity and PARP1 expression. Early inhibition of NF-κB and AP-1 activity and TNF-α and IL-6 expression in early AMI can improve cardiac function and reduce myocardial damage.