山精胶囊对心肌缺血大鼠NF-κB信号通路相关凋亡蛋白表达的影响

Effects of Shanjing Capsule on NF-κB Signal Pathway Related Apoptotic Proteins Against Myocardial Ishemia/Reperfusion Injury in Rats

摘要:

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324.0 mg·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.

Abstract:

Objective: To study the effect of ShanJing capsule on nuclear transcription factor-κB (NF-κB) signal pathway relating apoptosis proteins caspases-3 (Caspase-3), anti-apoptotic genes B cell lymphoma/leukemia-2(Bcl-2), pro-apoptotic genes Bcl-2 associated X protein(Bax), explore its protective effects on myocardial ischemia and mechanisms. Method: Wistar rats the coronary artery of which were ligated were used for myocardial ischemia model, the changes of the ST section in electrocardiogram(ECG) were observed, and randomly divided into 5 groups:model (0.9% sodium chloride), Shanjing capsule high, medium and low dose (respectively 283.5, 850.5,1 701.0 mg·kg^-1), Metoprolol capsules(324.0 mg·kg^-1), compared with sham group (0.9% sodium chloride). All groups were administered once daily for 10 days. The ST segment,serum lactate dehydrogenase (LDH), creatine kinase (CK), aspartate aminotransferase (AST) levels were observed. Immunohistochemistry was used to detect the NF-κB, Caspase-3, Bax, Bcl-2 protein of myocardial tissue. Result: Compared with the sham group, ST segment elevation was significantly raised (P <0.05), LDH, CK and AST activity was significantly higher (P <0.05), NF-κB, Caspase-3, Bax's protein expression levels of myocardial tissue were significantly higher (P <0.05), Bcl-2 protein expression was significantly lower (P <0.05) in the model group;Shanjing capsule could obviously ameliorate the raise of ST segment, and lower activity of CK, LDH and AST. Shanjing capsule could obviously decrease the protein expressions of NF-κB, Caspase-3 and Bax and increase the protein expression of Bcl-2. Conclusion: Shanjing capsule could regulate the expressions of NF-κB signaling pathway relating proteins, inhibit the myocardial apoptosis and reduce ischemia anoxic pathological damage of myocardial muscle cells to protect the myocardial muscle.