开心胶囊抗内皮损伤的作用机制研究
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摘要
冠心病是当前世界范围内严重威胁公众健康的重要疾病之一。统计资料表明,发达国家心血管病的发病率虽然有所下降,但是死亡率仍居首位。近年来,我国心血管病的死亡率有增加的趋势。因此,对冠心病发病机理和防治的研究是心血管病学的一个重要课题。其发病机制经历了多种学说,目前比较公认的是损伤反应学说。多种因素促进内皮损伤,导致动脉粥样硬化及冠心病的发生和发展。已知内皮功能不全不仅是动脉粥样硬化及冠心病发生的始动环节,而且在该病的发展过程中起着极其重要的作用。
开心胶囊是导师陈镜合教授根据多年临床经验研制而成的,既往研究表明,开心胶囊对无症状心肌缺血、心梗后心室重塑、缺血性心肌病继发的早期心力衰竭及心肺复苏后心功能不全等的临床和实验研究均得到了良好的疗效。开心胶囊是由越鞠丸、失笑散及生脉散加减而成的,具有行气解郁、活血通络、养心安神之功效。临床实践证明,开心胶囊对气滞血瘀型冠心病心绞痛患者有肯定疗效。
本课题主要是探讨开心胶囊的抗内皮损伤作用,以期为该药的临床应用提供理论依据。实验部分探讨开心胶囊药物血清对于气滞血瘀型高脂血症损伤人脐静脉内皮细胞的保护机制;临床部分验证开心胶囊对于气滞血瘀型冠心病心绞痛的临床疗效及对该类患者内皮功能的影响。本课题分文献研究、实验研究及临床研究三部展开。
文献研究:归纳了古代医家对本病的病名、病因病机、治则、治法等几个方面的认识;另外,归纳了现代中医研究较为详细的治疗内皮功能不全的中药单味药及复方。最后,阐述了现代医学对内皮细胞功能不全的认识,包括内皮的生理功能、损伤因素、内皮功能不全在动脉粥样硬化及冠心病发生中的作用机制,以及治疗进展。
实验研究:目的:探讨开心胶囊对气滞血瘀型高脂血清损伤内皮的保护作用机制。方法:首次采用夹尾郁怒伤肝法和食饵法复制肝郁气滞血瘀高脂血症大鼠动物模型。采用血清药物学方法,制备不同剂量组的开心胶囊药物血清及阳性对照药立普妥的药物血清。运用RT-PCR法和ELISA法检测气滞血瘀型高脂血清损伤人脐静脉内皮细胞12小时后,HUVECs中MCP-1mRNA含量、NF-κB活性的变化及开心胶囊药物血清干预后两者的变化。结果:气滞血瘀型高脂血清刺激HUVECs 12小时后,MCP-1mRNA含量增加、NF-κB活性升高,与空白组比较,具有显著性差异(p<0.05);开心胶囊的高剂量组药物血清干预后两者均表现为下降趋势,与模型组比较,具有显著性差异(p<0.05),与立普妥药物血清组比较,无显著性差异(p>0.05)。结论:开心胶囊的高剂量组药物血清能够降低气滞血瘀型高脂血清刺激HUVECs后MCP-1mRNA的含量及NF-κB活
As we all know, coronary heart disease is one kind of disease which needs pre-diagnose. Endothelium is not only a barrier, but also the organ which performs the functions of autocrine, paracrine and endocrine.Being a early symptom of CHD, Endothelial dysfunction is the primary stage in atherosclerosis and CHD. The traditional Chinese medicine is verified to have the prospective effect on the treatment of endothelial dysfunction after many years clinical experiments.Kaixin capsule is developed by the professor Chen jinghe, which has been identified with the clinical and experimental effects on symptomless myocardial ischemia, myocardial infarction ventricle remodeling, cardiac insufficiency after ischemic cardiomyopathy and cardio-pulmonary resuscitation. Kaixin capsule is mainly composed of yuejuwan, shixiaosan and shengmaisan, which has a function of xingqijieyu, huoxuetongluo and yangxinanshen. The article aims to evaluate the effect of Kaixin capsule on the endothelial dysfunction, also explore the machanism of Kaixin capsule on the angina pectoris patients who has the syndromes of stagnation qi and blood. The article has three aspects, including literature investigation, experiment and clinical investigation.There aren't terms of coronary heart disease, atheroscelorosis and endothelial dysfunction respectively in traditional Chinese medicine (TCM).According to the pathogenesis and clinical situations of endothelial dysfunction, it looks like "Xiongbi, zhenxintong" described in traditional Chinese medicine. Meanwhile,the symptom, pathology, therapy, and featured traditional Chinese medicine of the ancient time will be introduced in the article, among which, some are still used and investigated in
treating of endothelial dysfunction nowadays. At last, there are some aspects about pathophysiology, treatment, and the mechanism of endothelial function in atherosclerosis.Experimental research Objective: To evaluate the effect of the serum of Kaixin absorped on MCP-lmRNA and NF- k B activity in cultured cells(HUVECs). Methods: Several groups of cultured HUVECs were incubated with different drugs:(l)the HUVECs were incubated with PBS for 12 hours.(2)in other groups HUVECs, the serum of Kaixin of different doses was added to the cultured medium for 12 hours.(3) the HUVECs were cultured with Lipitor for 12 hours. The HUVECs MCP-1 mRNA was measured by quantitative competitive reverse transcription-polymerase chain reaction(RT-PCR). And the NF- k. B protein activity was measured by endothelial cell enzyme linked immunosorbent assay (ELISA).Results: Hyperlipidemic serum markedly increased HUVECs' MCP-1 mRNA expression after 12 hours incubation (p<0.05). After treatmemt with different dose of Kaixin capsule serum for 12 hours, MCP-1 mRNA expression was decreased ,0.48 ± 0.07,0.25 ± 0.02,0.21 ± 0.03 of lipitor group. There was no significant difference between the serum of high dose of kaixin and Lipitor group(p>0.05). The ELISA was performed to evaluate the effect of kaixin capsule on HUVECs. OD450 of NF- x B protein activity was 2.287±0.267, 2.147 + 0.356,1.141 ±0.107,0.108 ±0.095 respectively, in control group, OD450 was 0.935 ±0.086. The increase in NF- k B protein activity was significantly in model group, the activity of NF- k B was suppressed by treating with Kaixin capsule and Lipitor. There wsa no difference between Kaixin capsule of high dose and Lipitor group in NF- k B activity(p>0.05).Conclusion: 1 Hyperlipidemic serum markedly increased HUVECs MCP-1 mRNA expression and NF- k B activity. HUVECs MCP-lmRNA and NF- k B for 12 hours was decreased in HUVECs after incubated with the serum of Kaixin capsule and Lipitor. 2 The effects of endothelial dysfunction were blocked by pretreatment of HUVECs with Kaixin capsule .Kanxin capsule can lessen NF- k B activity and MCP-lmRNA expression, and Kaixin capsule may produce anti-endothelial dysfunction effect by this way.Clinical research Objective : To explore the effect and mechanism of traditional medicine Kaixin capsule in angina pectoris patients with the syndroms of stagnation qi and blood. Methods: Eighty cases of patients were selected, according to the
criteria of both the syndrom of stagnation qi and blood and of the coronary heart disease angina pectoris. All patients were allocated randomly to two groups: Kaixin group and the control group. Kaixin group were treated with Kaixin capsules, the control group were treated with Lunanxinkang. Before and after the treatment, the levels of hemorheology, NO, ET-1 were measured, and the score of the syndroms of the patients. Result: There was no significant difference between Kaixin group and Lunanxinkang group in clinical symptom total curative effect aspect. The total effective ratio of Kaixin group is 85%,the total effective ratio of Lunanxinkang group is 77.5% (P>0.05). But kaixin capsule can improve the syndrome of the stagnation of qi and blood better, such as touyuntoutong, shimianduomeng and aiqishantanxi. kaixin capsule can improve the ischemic changes in EKG, and there were no significant difference between two groups(P>0.05). In the aspect of hemorheology and hyperlipidemic, kaixin capsule can improve partly. Also, Kaixin capsule can lower the level of NO, ET-1.Conclusion: 1 kaixin capsule has a definite effect on angina pectoris patients with the syndrom of stagnation qi and blood. 2 kaixin capsule may have the ability of improving the endothelial dysfunction.
开心胶囊是导师陈镜合教授根据多年临床经验研制而成的,既往研究表明,开心胶囊对无症状心肌缺血、心梗后心室重塑、缺血性心肌病继发的早期心力衰竭及心肺复苏后心功能不全等的临床和实验研究均得到了良好的疗效。开心胶囊是由越鞠丸、失笑散及生脉散加减而成的,具有行气解郁、活血通络、养心安神之功效。临床实践证明,开心胶囊对气滞血瘀型冠心病心绞痛患者有肯定疗效。
本课题主要是探讨开心胶囊的抗内皮损伤作用,以期为该药的临床应用提供理论依据。实验部分探讨开心胶囊药物血清对于气滞血瘀型高脂血症损伤人脐静脉内皮细胞的保护机制;临床部分验证开心胶囊对于气滞血瘀型冠心病心绞痛的临床疗效及对该类患者内皮功能的影响。本课题分文献研究、实验研究及临床研究三部展开。
文献研究:归纳了古代医家对本病的病名、病因病机、治则、治法等几个方面的认识;另外,归纳了现代中医研究较为详细的治疗内皮功能不全的中药单味药及复方。最后,阐述了现代医学对内皮细胞功能不全的认识,包括内皮的生理功能、损伤因素、内皮功能不全在动脉粥样硬化及冠心病发生中的作用机制,以及治疗进展。
实验研究:目的:探讨开心胶囊对气滞血瘀型高脂血清损伤内皮的保护作用机制。方法:首次采用夹尾郁怒伤肝法和食饵法复制肝郁气滞血瘀高脂血症大鼠动物模型。采用血清药物学方法,制备不同剂量组的开心胶囊药物血清及阳性对照药立普妥的药物血清。运用RT-PCR法和ELISA法检测气滞血瘀型高脂血清损伤人脐静脉内皮细胞12小时后,HUVECs中MCP-1mRNA含量、NF-κB活性的变化及开心胶囊药物血清干预后两者的变化。结果:气滞血瘀型高脂血清刺激HUVECs 12小时后,MCP-1mRNA含量增加、NF-κB活性升高,与空白组比较,具有显著性差异(p<0.05);开心胶囊的高剂量组药物血清干预后两者均表现为下降趋势,与模型组比较,具有显著性差异(p<0.05),与立普妥药物血清组比较,无显著性差异(p>0.05)。结论:开心胶囊的高剂量组药物血清能够降低气滞血瘀型高脂血清刺激HUVECs后MCP-1mRNA的含量及NF-κB活
As we all know, coronary heart disease is one kind of disease which needs pre-diagnose. Endothelium is not only a barrier, but also the organ which performs the functions of autocrine, paracrine and endocrine.Being a early symptom of CHD, Endothelial dysfunction is the primary stage in atherosclerosis and CHD. The traditional Chinese medicine is verified to have the prospective effect on the treatment of endothelial dysfunction after many years clinical experiments.Kaixin capsule is developed by the professor Chen jinghe, which has been identified with the clinical and experimental effects on symptomless myocardial ischemia, myocardial infarction ventricle remodeling, cardiac insufficiency after ischemic cardiomyopathy and cardio-pulmonary resuscitation. Kaixin capsule is mainly composed of yuejuwan, shixiaosan and shengmaisan, which has a function of xingqijieyu, huoxuetongluo and yangxinanshen. The article aims to evaluate the effect of Kaixin capsule on the endothelial dysfunction, also explore the machanism of Kaixin capsule on the angina pectoris patients who has the syndromes of stagnation qi and blood. The article has three aspects, including literature investigation, experiment and clinical investigation.There aren't terms of coronary heart disease, atheroscelorosis and endothelial dysfunction respectively in traditional Chinese medicine (TCM).According to the pathogenesis and clinical situations of endothelial dysfunction, it looks like "Xiongbi, zhenxintong" described in traditional Chinese medicine. Meanwhile,the symptom, pathology, therapy, and featured traditional Chinese medicine of the ancient time will be introduced in the article, among which, some are still used and investigated in
treating of endothelial dysfunction nowadays. At last, there are some aspects about pathophysiology, treatment, and the mechanism of endothelial function in atherosclerosis.Experimental research Objective: To evaluate the effect of the serum of Kaixin absorped on MCP-lmRNA and NF- k B activity in cultured cells(HUVECs). Methods: Several groups of cultured HUVECs were incubated with different drugs:(l)the HUVECs were incubated with PBS for 12 hours.(2)in other groups HUVECs, the serum of Kaixin of different doses was added to the cultured medium for 12 hours.(3) the HUVECs were cultured with Lipitor for 12 hours. The HUVECs MCP-1 mRNA was measured by quantitative competitive reverse transcription-polymerase chain reaction(RT-PCR). And the NF- k. B protein activity was measured by endothelial cell enzyme linked immunosorbent assay (ELISA).Results: Hyperlipidemic serum markedly increased HUVECs' MCP-1 mRNA expression after 12 hours incubation (p<0.05). After treatmemt with different dose of Kaixin capsule serum for 12 hours, MCP-1 mRNA expression was decreased ,0.48 ± 0.07,0.25 ± 0.02,0.21 ± 0.03 of lipitor group. There was no significant difference between the serum of high dose of kaixin and Lipitor group(p>0.05). The ELISA was performed to evaluate the effect of kaixin capsule on HUVECs. OD450 of NF- x B protein activity was 2.287±0.267, 2.147 + 0.356,1.141 ±0.107,0.108 ±0.095 respectively, in control group, OD450 was 0.935 ±0.086. The increase in NF- k B protein activity was significantly in model group, the activity of NF- k B was suppressed by treating with Kaixin capsule and Lipitor. There wsa no difference between Kaixin capsule of high dose and Lipitor group in NF- k B activity(p>0.05).Conclusion: 1 Hyperlipidemic serum markedly increased HUVECs MCP-1 mRNA expression and NF- k B activity. HUVECs MCP-lmRNA and NF- k B for 12 hours was decreased in HUVECs after incubated with the serum of Kaixin capsule and Lipitor. 2 The effects of endothelial dysfunction were blocked by pretreatment of HUVECs with Kaixin capsule .Kanxin capsule can lessen NF- k B activity and MCP-lmRNA expression, and Kaixin capsule may produce anti-endothelial dysfunction effect by this way.Clinical research Objective : To explore the effect and mechanism of traditional medicine Kaixin capsule in angina pectoris patients with the syndroms of stagnation qi and blood. Methods: Eighty cases of patients were selected, according to the
criteria of both the syndrom of stagnation qi and blood and of the coronary heart disease angina pectoris. All patients were allocated randomly to two groups: Kaixin group and the control group. Kaixin group were treated with Kaixin capsules, the control group were treated with Lunanxinkang. Before and after the treatment, the levels of hemorheology, NO, ET-1 were measured, and the score of the syndroms of the patients. Result: There was no significant difference between Kaixin group and Lunanxinkang group in clinical symptom total curative effect aspect. The total effective ratio of Kaixin group is 85%,the total effective ratio of Lunanxinkang group is 77.5% (P>0.05). But kaixin capsule can improve the syndrome of the stagnation of qi and blood better, such as touyuntoutong, shimianduomeng and aiqishantanxi. kaixin capsule can improve the ischemic changes in EKG, and there were no significant difference between two groups(P>0.05). In the aspect of hemorheology and hyperlipidemic, kaixin capsule can improve partly. Also, Kaixin capsule can lower the level of NO, ET-1.Conclusion: 1 kaixin capsule has a definite effect on angina pectoris patients with the syndrom of stagnation qi and blood. 2 kaixin capsule may have the ability of improving the endothelial dysfunction.
引文
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