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目的:研究山精胶囊对心肌缺血大鼠核转录因子-κB(NF-κB)信号通路相关凋亡蛋白半胱氨酸蛋白酶-3(Caspase-3),抗细胞凋亡B细胞淋巴瘤/白血病2基因(Bcl-2),促细胞凋亡Bcl-2相关X蛋白基因(Bax)表达的影响,探讨其对心肌缺血的保护作用和机制。方法:采用冠状动脉结扎法造模,4周后进行心电图检测,提示慢性心肌缺血模型成功,并筛选分组。山精胶囊低、中、高剂量组ig给药剂量分别为283.5,850.5,1 701.0 mg·kg-1;阳性药心安胶囊ig给药剂量为324.0mg·kg-1。假手术组和模型组ig给予同等剂量的0.9%的氯化钠注射液。每日ig给药1次,连续给药10 d。以心电图法观察其对大鼠心电图ST段的影响,检测血清中乳酸脱氢酶(LDH),肌酸激酶(CK),天冬氨酸转氨酶(AST)的含量,免疫组化法检测心肌组织中NF-κB,Caspase-3,Bax,Bcl-2蛋白的表达。结果:与假手术组相比,模型组ST段显著抬高(P<0.05),LDH,CK和AST活性显著升高(P<0.05),心肌组织中的NF-κB,Caspase-3,Bax的蛋白表达水平显著增高(P<0.05),Bcl-2蛋白表达水平显著降低(P<0.05);与模型组比较山精胶囊能明显抑制心肌缺血大鼠的ST段抬高,降低血清心肌酶LDH,CK,AST的活性(P<0.05),显著降低NF-κB,Caspase-3,Bax蛋白表达(P<0.05),提高Bcl-2的蛋白表达(P<0.05)。结论:山精胶囊可能是通过调控NF-κB信号通路相关凋亡蛋白的表达,抑制心肌细胞凋亡,减少缺血缺氧对心肌细胞的病理损害,起到对心肌的保护作用。
Objective: To investigate the effect of shangjing capsule on the expression of caspase-3, anti-apoptotic B-cell lymphoma and anti-apoptotic protein in nuclear factor-kappa B (NF- (Bcl-2, Bcl-2, Bcl-2 and Bcl-2) in cardiomyocytes, and to explore its protective effect on myocardial ischemia. Methods: The model of coronary artery ligation was made. Electrocardiogram was taken after 4 weeks, which indicated that the model of chronic myocardial ischemia was successfully established and screened. The doses of shanjing capsule were 283.5, 850.5 and 1 701.0 mg · kg-1 for low, medium and high dose groups respectively, and 324.0 mg · kg-1 for the positive drug xinan capsule. Sham operation group and model group ig given the same dose of 0.9% sodium chloride injection. Daily ig administration 1, continuous administration of 10 d. The electrocardiogram (ECG) was used to observe the effect on ST segment of electrocardiogram in rats. The content of lactate dehydrogenase (LDH), creatine kinase (CK) and aspartate aminotransferase (AST) NF-κB, Caspase-3, Bax, Bcl-2 protein expression. Results: Compared with sham operation group, the ST segment in model group was significantly increased (P <0.05), while the activities of LDH, CK and AST were significantly increased (P <0.05). The levels of NF-κB, Caspase-3, Bax (P <0.05), while the expression of Bcl-2 protein decreased significantly (P <0.05). Compared with the model group, shangjing capsule could significantly inhibit the ST segment elevation in myocardial ischemia rats and decrease the level of serum myocardial (P <0.05), and significantly decreased the expression of NF-κB, Caspase-3 and Bax (P <0.05), and increased the protein expression of Bcl-2 (P <0.05). Conclusion: Shanjing Capsule may play a protective role on myocardium through regulating the expression of apoptosis-related proteins of NF-κB signaling pathway, inhibiting cardiomyocyte apoptosis, reducing the pathological damage of myocardial cells by hypoxia and hypoxia.