麝香保心丸干预急性心肌梗死模型大鼠心室重构的实验研究
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摘要
目的：评价麝香保心丸对实验性心肌梗死(AMI)模型大鼠心室重构的干预作用。
方法：应用冠状动脉结扎法结扎大鼠冠状动脉左前降支造成急性心肌梗死模型,对比观察中成药麝香保心丸与西药卡托普利对心肌梗死模型大鼠心室重构的影响及对血管紧张素Ⅱ(AngⅡ).脑钠素(BNP)的影响,对麝香保心丸改善心室重构的机理做了初步探讨。60只SD大鼠完全随机分组,前9只作为空白对照组,余下51只大鼠造模,成功36只。将造模成功的36只模型大鼠随机分为4个组,模型组、麝香保心丸等剂量组、麝香保心丸大剂量组、卡托普利组,每组9只。空白对照组对照予常饲养不予任何干预；模型组每日灌胃一次,予生理盐水按1ml／100g计算；麝香保心丸等剂量组在心肌梗死造模后第2天始,每天予麝香保心丸溶液1.16ml/100g(6.75mg/ml)灌胃,1次／日；麝香保心丸大剂量组在造模第2天始,每天予麝香保心丸溶液1.16ml/100g(20.25mg/ml)灌胃,1次／日；卡托普利组在心肌梗死造模第2天始,每天予卡托普利溶液1.1ml/100g(5mg/ml),1次／日。除空白对照组对照组外,各组大鼠每周均称体重后调整给药或生理盐水剂量,灌胃至取材时。造模成功后每日观察各组大鼠一般生命状况,包括精神状态、毛发、饮食、饮水量、活动及反应度等。灌胃满2周时予以测定大鼠的血流动力学参数,用ELISA法测定其血浆BNP、AngⅡ、血管紧张素AT1、AT2受体抗体含量,称大鼠左室重量并除以其体重,计算其左室重量指数,取缺血及其边缘心肌组织行HE染色和Masson染色后做光镜检查和免疫组化检测组织AT1、AT2受体,并进行透射电镜超微结构观察。
结果：麝香保心丸大剂量、麝香保心丸等剂量和卡托普利均可以改善AMI后大鼠的一般生命状况和血流动力学参数,均能改善大鼠AMI后心肌组织结构和病理学变化,减轻AMI后非梗死区组织胶原含量增加,均可降低AMI后大鼠的AT1受体和升高AT2受体,降低血浆BNP、AngⅡ,改善AMI后心室重构。
结论：麝香保心丸大剂量、麝香保心丸等剂量均能改善心梗后模型大鼠的肾素-血管紧张素-醛固酮系统的激活,改善大鼠血流动力学,改善梗死心肌及其周围心肌的组织病理变化,其作用可能通过降低心肌局部和循环中的AngⅡ、AT1受体和升高AT2受体而实现的。麝香保心丸对AMI模型大鼠神经内分泌的调节作用与血管紧张素转换酶抑制剂(ACEI)部分相似,可改善模型大鼠的心室重构。
1. Objective:To evaluate Heart-Protection Musk Pill on experimental rat model of myocardial infarction ventricular remodeling in rats.
2. Methods:In this study, ligation of left anterior descending coronary artery caused acute myocardial infarction model, comparative observation of proprietary Chinese medicines with Western drug HMP captopril rat model of myocardial infarction and ventricular remodeling by angiotensinⅡ, brain natriuretic peptide and HMP improve ventricular remodeling mechanism has been discussed, while exploring the size of the dose of HMP on Rat ventricular remodeling with or without different.60 SD rats were completely randomized, pre-9 as control group, the remaining 51 rats through the junction of left anterior descending coronary artery caused acute myocardial infarction model, The model was successful 36 rats were randomly divided into four group, model group, dose Shexiangbaoxin balls, HMP high dose group, captopril group, n= 9. In addition to keeping control group not often that any intervention; model group fed once a day, to the calculation of normal saline by 1ml/100g; Heart Heart-Protection Musk Pill (HMP)dose modeling in myocardial infarction 2 days after the beginning of each day to Musk Pill 1.16ml/100g (6.75mg/ml),1 times/day; HMP modeling high-dose group until day 2 days to HMP 1.16ml/100g (20.25mg/ml),1 times/ day; captopril tablets group modeling in myocardial infarction 2 days before tablets a day for captopril solution 1.1ml/100g (5mg/ml),1 times/day; Weighed in each group after 1 week after dose adjustments when fed to drawn. All because of anesthesia accidents, trauma and other causes of death and survival time after time requirements have not yet drawn up the animals, the observed test statistics are not included within the scope of the project. After the modeling, the rats were observed daily general life circumstances such as:mental health, hair, diet, water intake, activity and reaction degree. To be given medicines at least 2 weeks, hemodynAMIc parameters measured in rats using ELISA, the plasma brain natriuretic peptide (BNP), plasma angiotensinⅡ(AngⅡ), angiotensin AT1, AT2 receptor antibody levels that left ventricular weight and divided by its weight, calculated left ventricular mass index, ischeAMIc area were taken and the non-ischeAMIc myocardium, HE staining and Masson staining under light AMIcroscopy and immunohistocheAMIstry, and by transAMIssion transAMIssion electron AMIcroscopy observation.
3. RESULTS:The results showed that Heart-Protection Musk Pill of high-dose, dose and captonpril after AMI can improve the lives of the general situation and hemodynAMIcs, AMI can improve rats after a series of myocardial tissue ventricular structure and organization of pathological changes to reduce non-infarcted area after AMI collagen content increase can be reduced after AMI AT1 receptor in rats and increased AT2 receptor, improve ventricular remodeling after AMI. Heart-Protection Musk Pill of high-dose rat in improving AMI cardiac contractile function of the indicators of effective than Heart-Protection Musk Pill dose and captonpril; to improve cardiac diastolic function, Heart-Protection Musk Pill of high-dose, dose, the effect of captonpril the difference was not statistically significant.
4. Conclusion::HMP large doses, such doses inhibited after myocardial infarction in rats activation of renin-angiotensin-aldosterone system, improve hemodynAMIcs, thereby reducing myocardial infarction and surrounding pathological changes of the myocardium and reduce cardiac local and circulating AngⅡ, AT1 receptor and AT2 receptors increases achieved. Model of acute myocardial infarction on neuroendocrine function and regulation of angiotensin converting enzyme inhibitor (ACEI) were siAMIlar, reduce ventricular remodeling in rats.
方法：应用冠状动脉结扎法结扎大鼠冠状动脉左前降支造成急性心肌梗死模型,对比观察中成药麝香保心丸与西药卡托普利对心肌梗死模型大鼠心室重构的影响及对血管紧张素Ⅱ(AngⅡ).脑钠素(BNP)的影响,对麝香保心丸改善心室重构的机理做了初步探讨。60只SD大鼠完全随机分组,前9只作为空白对照组,余下51只大鼠造模,成功36只。将造模成功的36只模型大鼠随机分为4个组,模型组、麝香保心丸等剂量组、麝香保心丸大剂量组、卡托普利组,每组9只。空白对照组对照予常饲养不予任何干预；模型组每日灌胃一次,予生理盐水按1ml／100g计算；麝香保心丸等剂量组在心肌梗死造模后第2天始,每天予麝香保心丸溶液1.16ml/100g(6.75mg/ml)灌胃,1次／日；麝香保心丸大剂量组在造模第2天始,每天予麝香保心丸溶液1.16ml/100g(20.25mg/ml)灌胃,1次／日；卡托普利组在心肌梗死造模第2天始,每天予卡托普利溶液1.1ml/100g(5mg/ml),1次／日。除空白对照组对照组外,各组大鼠每周均称体重后调整给药或生理盐水剂量,灌胃至取材时。造模成功后每日观察各组大鼠一般生命状况,包括精神状态、毛发、饮食、饮水量、活动及反应度等。灌胃满2周时予以测定大鼠的血流动力学参数,用ELISA法测定其血浆BNP、AngⅡ、血管紧张素AT1、AT2受体抗体含量,称大鼠左室重量并除以其体重,计算其左室重量指数,取缺血及其边缘心肌组织行HE染色和Masson染色后做光镜检查和免疫组化检测组织AT1、AT2受体,并进行透射电镜超微结构观察。
结果：麝香保心丸大剂量、麝香保心丸等剂量和卡托普利均可以改善AMI后大鼠的一般生命状况和血流动力学参数,均能改善大鼠AMI后心肌组织结构和病理学变化,减轻AMI后非梗死区组织胶原含量增加,均可降低AMI后大鼠的AT1受体和升高AT2受体,降低血浆BNP、AngⅡ,改善AMI后心室重构。
结论：麝香保心丸大剂量、麝香保心丸等剂量均能改善心梗后模型大鼠的肾素-血管紧张素-醛固酮系统的激活,改善大鼠血流动力学,改善梗死心肌及其周围心肌的组织病理变化,其作用可能通过降低心肌局部和循环中的AngⅡ、AT1受体和升高AT2受体而实现的。麝香保心丸对AMI模型大鼠神经内分泌的调节作用与血管紧张素转换酶抑制剂(ACEI)部分相似,可改善模型大鼠的心室重构。
1. Objective:To evaluate Heart-Protection Musk Pill on experimental rat model of myocardial infarction ventricular remodeling in rats.
2. Methods:In this study, ligation of left anterior descending coronary artery caused acute myocardial infarction model, comparative observation of proprietary Chinese medicines with Western drug HMP captopril rat model of myocardial infarction and ventricular remodeling by angiotensinⅡ, brain natriuretic peptide and HMP improve ventricular remodeling mechanism has been discussed, while exploring the size of the dose of HMP on Rat ventricular remodeling with or without different.60 SD rats were completely randomized, pre-9 as control group, the remaining 51 rats through the junction of left anterior descending coronary artery caused acute myocardial infarction model, The model was successful 36 rats were randomly divided into four group, model group, dose Shexiangbaoxin balls, HMP high dose group, captopril group, n= 9. In addition to keeping control group not often that any intervention; model group fed once a day, to the calculation of normal saline by 1ml/100g; Heart Heart-Protection Musk Pill (HMP)dose modeling in myocardial infarction 2 days after the beginning of each day to Musk Pill 1.16ml/100g (6.75mg/ml),1 times/day; HMP modeling high-dose group until day 2 days to HMP 1.16ml/100g (20.25mg/ml),1 times/ day; captopril tablets group modeling in myocardial infarction 2 days before tablets a day for captopril solution 1.1ml/100g (5mg/ml),1 times/day; Weighed in each group after 1 week after dose adjustments when fed to drawn. All because of anesthesia accidents, trauma and other causes of death and survival time after time requirements have not yet drawn up the animals, the observed test statistics are not included within the scope of the project. After the modeling, the rats were observed daily general life circumstances such as:mental health, hair, diet, water intake, activity and reaction degree. To be given medicines at least 2 weeks, hemodynAMIc parameters measured in rats using ELISA, the plasma brain natriuretic peptide (BNP), plasma angiotensinⅡ(AngⅡ), angiotensin AT1, AT2 receptor antibody levels that left ventricular weight and divided by its weight, calculated left ventricular mass index, ischeAMIc area were taken and the non-ischeAMIc myocardium, HE staining and Masson staining under light AMIcroscopy and immunohistocheAMIstry, and by transAMIssion transAMIssion electron AMIcroscopy observation.
3. RESULTS:The results showed that Heart-Protection Musk Pill of high-dose, dose and captonpril after AMI can improve the lives of the general situation and hemodynAMIcs, AMI can improve rats after a series of myocardial tissue ventricular structure and organization of pathological changes to reduce non-infarcted area after AMI collagen content increase can be reduced after AMI AT1 receptor in rats and increased AT2 receptor, improve ventricular remodeling after AMI. Heart-Protection Musk Pill of high-dose rat in improving AMI cardiac contractile function of the indicators of effective than Heart-Protection Musk Pill dose and captonpril; to improve cardiac diastolic function, Heart-Protection Musk Pill of high-dose, dose, the effect of captonpril the difference was not statistically significant.
4. Conclusion::HMP large doses, such doses inhibited after myocardial infarction in rats activation of renin-angiotensin-aldosterone system, improve hemodynAMIcs, thereby reducing myocardial infarction and surrounding pathological changes of the myocardium and reduce cardiac local and circulating AngⅡ, AT1 receptor and AT2 receptors increases achieved. Model of acute myocardial infarction on neuroendocrine function and regulation of angiotensin converting enzyme inhibitor (ACEI) were siAMIlar, reduce ventricular remodeling in rats.
引文
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