从炎症通路探讨心宁片抗心肌缺血的疗效与作用机理
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摘要
目的:评价心宁片对冠心病心绞痛的临床疗效,并从炎症信号通路探讨其抗心肌缺血的作用。
方法:1.采用循证医学和DME方法,观察心宁片对稳定性心绞痛患者的临床疗效、心电图、硝酸甘油用量及炎症因子TNF-α,IL-1的影响,并与地尔硫卓比较。
2.采用冠状动脉结扎复制心肌缺血损伤模型,随机分组,分别给药,于术后12、24h处死动物,采用ELISA、免疫组化和PCR方法检测TNF-α,IL-1,VCAM-1,NO,NFkB和IkB的含量与表达。
结果:1.心宁片治疗心绞痛总有效率为87.8%,心电图疗效总有效率为72.7%,证候总有效率为90.9%,明显优于对照组的75.0%,65.6%和81.3%(p＜0.05),且能明显改善胸闷、胸痛症状和血清TNF-α,IL-1水平(p＜0.05)。
2.在正常大鼠心脏有一定量的TNF-α和VCAM-1表达,心肌缺血损伤后两者表达明显增强,地尔硫卓和心宁片均能下调其表达,与模型组比较,差异有显著性P＜0.05或P＜0.01;心宁片组与地尔硫(艹卓)组TNF-α比较差异有显著性,P＜0.05,但在VCAM-1差异无显著性P＞0.05。
3.IL-1,iNos在正常大鼠血清有一定水平的表达,心肌缺血后两者含量迅速增加,给予心宁和地尔硫卓下调IL-1、iNos,两组与模型组差异有显著性,且两组间差异亦有显著性,P＜0.05。
4.正常情况下NFkBP65、IKB有较低水平的表达,心肌缺血损伤后NFkBP65增加IKB表达被抑制,地尔硫卓和心宁片均能下调NFkBP65的表达,上调IKB,与模型组比较,差异有显著性,P＜0.05,且地尔硫卓不如心宁片,P＜0.05。
结论:1.心宁片能明显改善冠心病心绞痛患者的心电图、心肌缺血情况和症状,调节血清炎症因子的水平,是较理想的抗心绞痛药物。
2.心宁片能明显改善心肌缺血大鼠的炎症因子,下调血管粘附因子-1和NO激酶,调节核转录因子kB和IkB的表达,影响炎症信号通路是其可能作用机理之一。
Objective:To evaluate clinical effect of Xinning tablets on Angina and explore its anti-myocardial ischemia mechanism from the inflammatory signaling pathway.
Method:1.According evidence-based medicine and DME,the clinical and ECG,nitroglycerin consumption effects of Xinning tablets on patients with stable angina was observed,and inflammatory cytokines TNF,IL-1 in patients serum was checked,and compared with diltiazem.
2.Using coronary artery ligation induced myocardial ischemia model, animals were randomized,administrated respectively and killed at 12,24 hour after operation,level and expression of TNF-α,IL-1,VCAM-1,NO, NFkB family proteins were cheched using ELISA and immunohistochemistry and PCR method.
Results:1.Total efficiency,incidence of total efficiency and syndromes of the total efficiency on angina of Xinning tablet was 87.8%,72.7%and 90.9%,that was significantly better than that of the control group(75.0%, 65.6%and 81.3%)(p＜0.05),but also Xinning tablet can significantly improve chest tightness,chest pain symptoms and serum levels of TNF-αand IL-1(p＜0.05).
2.There was a certain amount of expression of VCAM-1 and TNF-αin the normal heart,after myocardial ischemia both were increased significantly, diltiazem and Xinning can reduced expression of VCAM-1 and TNF-α, compared with the model group,The difference was significant(P＜0.05),the difference of TNF-αbetween Xinning group and diltiazem was also significant,P＜0.05,but in VCAM-1 there was not significant difference p＞0.05.
3.There was certain level of IL-1,iNOS in normal rat serum,both were rapid increase after myocardial ischemia,Xinning and diltiazem can reduce level of IL-1,iNOS,compared with model group the difference was significant,and differences between Xinning and diltiazem was significant,P＜0.05.
4.Under normal circumstances NFkBP65 and IkB had lower levels of expression,after Myocardial ischemia expression of NFkBP65 was increased but that of IkB was inhibited,Diltiazem and Xinning tablets can reduce NFkBP65 expression and increase IkB expression,compared with model group,the difference was significant,P＜0.05;and there was significant between diltiazem and Xinning tablets,P＜0.05.
Conclusions:1.Xinning tablet can significantly improve clinicl efficacy the electrocardiogram,myocardial ischemia and symptoms of angina pectoris, and regulate serum cytokine levels,that shows it is an ideal anti - angina drugs.
2.Xinning tablet can significantly improve cytokines in myocardial ischemia rat,reduce vascular adhesion molecule-1 and NO kinase,regulate of NF-kB activation and the expression of IjB,That is one possible mechanism against ischemia affected inflammatory signaling pathways.
方法:1.采用循证医学和DME方法,观察心宁片对稳定性心绞痛患者的临床疗效、心电图、硝酸甘油用量及炎症因子TNF-α,IL-1的影响,并与地尔硫卓比较。
2.采用冠状动脉结扎复制心肌缺血损伤模型,随机分组,分别给药,于术后12、24h处死动物,采用ELISA、免疫组化和PCR方法检测TNF-α,IL-1,VCAM-1,NO,NFkB和IkB的含量与表达。
结果:1.心宁片治疗心绞痛总有效率为87.8%,心电图疗效总有效率为72.7%,证候总有效率为90.9%,明显优于对照组的75.0%,65.6%和81.3%(p＜0.05),且能明显改善胸闷、胸痛症状和血清TNF-α,IL-1水平(p＜0.05)。
2.在正常大鼠心脏有一定量的TNF-α和VCAM-1表达,心肌缺血损伤后两者表达明显增强,地尔硫卓和心宁片均能下调其表达,与模型组比较,差异有显著性P＜0.05或P＜0.01;心宁片组与地尔硫(艹卓)组TNF-α比较差异有显著性,P＜0.05,但在VCAM-1差异无显著性P＞0.05。
3.IL-1,iNos在正常大鼠血清有一定水平的表达,心肌缺血后两者含量迅速增加,给予心宁和地尔硫卓下调IL-1、iNos,两组与模型组差异有显著性,且两组间差异亦有显著性,P＜0.05。
4.正常情况下NFkBP65、IKB有较低水平的表达,心肌缺血损伤后NFkBP65增加IKB表达被抑制,地尔硫卓和心宁片均能下调NFkBP65的表达,上调IKB,与模型组比较,差异有显著性,P＜0.05,且地尔硫卓不如心宁片,P＜0.05。
结论:1.心宁片能明显改善冠心病心绞痛患者的心电图、心肌缺血情况和症状,调节血清炎症因子的水平,是较理想的抗心绞痛药物。
2.心宁片能明显改善心肌缺血大鼠的炎症因子,下调血管粘附因子-1和NO激酶,调节核转录因子kB和IkB的表达,影响炎症信号通路是其可能作用机理之一。
Objective:To evaluate clinical effect of Xinning tablets on Angina and explore its anti-myocardial ischemia mechanism from the inflammatory signaling pathway.
Method:1.According evidence-based medicine and DME,the clinical and ECG,nitroglycerin consumption effects of Xinning tablets on patients with stable angina was observed,and inflammatory cytokines TNF,IL-1 in patients serum was checked,and compared with diltiazem.
2.Using coronary artery ligation induced myocardial ischemia model, animals were randomized,administrated respectively and killed at 12,24 hour after operation,level and expression of TNF-α,IL-1,VCAM-1,NO, NFkB family proteins were cheched using ELISA and immunohistochemistry and PCR method.
Results:1.Total efficiency,incidence of total efficiency and syndromes of the total efficiency on angina of Xinning tablet was 87.8%,72.7%and 90.9%,that was significantly better than that of the control group(75.0%, 65.6%and 81.3%)(p＜0.05),but also Xinning tablet can significantly improve chest tightness,chest pain symptoms and serum levels of TNF-αand IL-1(p＜0.05).
2.There was a certain amount of expression of VCAM-1 and TNF-αin the normal heart,after myocardial ischemia both were increased significantly, diltiazem and Xinning can reduced expression of VCAM-1 and TNF-α, compared with the model group,The difference was significant(P＜0.05),the difference of TNF-αbetween Xinning group and diltiazem was also significant,P＜0.05,but in VCAM-1 there was not significant difference p＞0.05.
3.There was certain level of IL-1,iNOS in normal rat serum,both were rapid increase after myocardial ischemia,Xinning and diltiazem can reduce level of IL-1,iNOS,compared with model group the difference was significant,and differences between Xinning and diltiazem was significant,P＜0.05.
4.Under normal circumstances NFkBP65 and IkB had lower levels of expression,after Myocardial ischemia expression of NFkBP65 was increased but that of IkB was inhibited,Diltiazem and Xinning tablets can reduce NFkBP65 expression and increase IkB expression,compared with model group,the difference was significant,P＜0.05;and there was significant between diltiazem and Xinning tablets,P＜0.05.
Conclusions:1.Xinning tablet can significantly improve clinicl efficacy the electrocardiogram,myocardial ischemia and symptoms of angina pectoris, and regulate serum cytokine levels,that shows it is an ideal anti - angina drugs.
2.Xinning tablet can significantly improve cytokines in myocardial ischemia rat,reduce vascular adhesion molecule-1 and NO kinase,regulate of NF-kB activation and the expression of IjB,That is one possible mechanism against ischemia affected inflammatory signaling pathways.
引文
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