基于L型钙电流研究益气药干预心衰电生理重构机制
发布时间：2018-07-21 12:48
【摘要】：心力衰竭(心衰,heart failure, HF)是21世纪危害人类健康的重要心血管疾病,心衰患者5年生存率约为50%,其中D期心衰患者恶性心律失常的发生率明显增加,近50%患者死于恶性心律失常所导致的心源性猝死。电生理重构导致的恶性心律失常是心一衰患者死亡的重要原因之一。电生理重构是指在心衰时,由于病理生理机制发生变化,导致心肌细胞电冲动产生及传导机制发生的改变,涉及多种离子通道和细胞信号转导系统的功能改变,其中L型钙电流改变和动作电位时程(Action potential duration, APD)延长是关键环节。目前仍缺乏针对心衰电生理重构的有效药物可供临床选择,中医药研究有可能是解决这一问题的突破口。中医认为心气虚是心衰的基本病机,贯穿于心衰发生发展始终,益气药是中医防治心衰的一类基本药物,能够改善心衰患者心功能及临床症状,提高患者生存质量。黄芪、党参、人参是临床常用的益气药。目前已知的中医药作用机制具有多层次、多环节、多靶点等特点,前期研究从能量代谢和肌浆网钙转运角度探讨了益气药改善心衰模型心功能的作用机制,但从电生理重构角度探讨益气药改善心衰模型预后的机制研究还未见诸报道。本研究通过复制结扎冠脉所致心梗后心衰、缩窄主动脉所致压力负荷心衰两种小鼠模型,运用小动物超声心动图、心电图、全细胞膜片钳技术及Western Blot分子生物学方法,从整体、细胞、分子层面进行研究,以验证“益气药可能通过抑制钙/钙调素依赖性蛋白激酶Ⅱ(calcium/calmodulin-dependent protein kinase II, CaMKII)过表达,调控心衰细胞L型钙电流,缩短心衰心肌细胞及心脏复极时间,改善心衰电生理重构”的科学假说。方法1.动物造模：采用冠脉结扎术、主动脉缩窄术分别复制心梗后心衰、压力负荷心衰两种小鼠模型；2.分组和给药：(1)冠脉结扎术后小鼠随机分为模型组、假手术组、益气组(黄芪+党参)、西药组(美托洛尔)4组,术后给予相应药物干预4周；(2)主动脉缩窄术后小鼠随机分为模型组、假手术组、黄芪组(黄芪)、人参组(人参)、党参组(党参)、西药组(美托洛尔)6组,术后给予相应药物干预4周；3.检测方法：(1)冠脉结扎术后4周小鼠和主动脉缩窄术后4周小鼠记录体重、死亡等一般情况,利用小动物超声心动图检测心脏收缩、舒张功能及心室重构情况,利用心电图检测QT间期及室性心律失常发生率；(2)主动脉缩窄术后4周小鼠急性分离心肌细胞,利用全细胞膜片钳技术的电流钳模式记录心肌细胞APD,利用全细胞电压钳模式记录L型钙电流密度、失活时间常数(T)以及电压依赖性激活-失活曲线;(3)主动脉缩窄术后4周小鼠处死取心肌组织,应用Western Blot技术检测L型钙通道、CaMKII的蛋白表达水平。结果1.心衰模型的评价：(1)冠脉结扎术后4周模型小鼠与假手术组相比左室射血分数(left ventricular ejection fraction, LVEF)显著下降(p0.01),舒张末左室内径显著增加(p0.01),校正QT间期(QTc)显著延长(p0.01)；(2)主动脉缩窄术后4周模型小鼠与假手术组相比LVEF显著下降(p0.01),收缩末左室内径增加(p0.05),左室前壁厚度显著增加(p0.01),Ea显著降低(p0.01), QTc显著延长(p0.01)。2. 益气药对心衰小鼠心功能及QT间期的干预作用：(1)冠脉结扎术后4周,益气组与模型组相比LVEF有升高趋势但无统计学意义,西药组与模型组相比LVEF无显著差异,益气组、西药组与模型组相比QTc均显著缩短(p0.01)；(2)主动脉缩窄术后4周,黄芪组与模型组相比LVEF升高(p0.05),Ea显著升高(p0.01),党参组与模型组相比LVEF显著升高(p0.01)；黄芪组、人参组、党参组与模型组相比QTc均显著缩短(p0.01)。3.益气药对心衰细胞APD及L型钙电流的干预作用：(1)APD:模型组与假手术组相比,在0.21、2.0Hz频率刺激下心肌细胞动作电位复极90%时间(APD90)均显著延长(p0.01)；黄芪组与模型组相比,在0.2Hz、2.0Hz频率刺激下心肌细胞APD90缩短(p0.05)；党参组与模型组相比,在0.2Hz、2.0Hz频率刺激下心肌细胞APD90显著缩短(p0.01),并且在异丙肾上腺素(isoprenaline, ISO)干预下与模型组相比APD90缩短(p0.05);(2) ICa,L电流密度：模型组与假手术组相比,在0.1Hz、1.0Hz刺激下ICa,L电流密度均显著增大(p0.01);黄芪组与模型组相比,1.0Hz刺激下ICa,L电流密度显著减小(p0.01);党参组与模型组相比,0.1 Hz、1.0Hz刺激下ICa,L电流密度均减小(p0.01、p0.05),并且在ISO干预下ICa,L电流密度与模型组相比减小(p0.05)；(3)Ica,L失活时间常数：模型组与假手术组相比ICa,L快速失活时间常数(τ1)和慢速失活时间常数(τ 2)均显著延长(p0.01),黄芪组、人参组、党参组与模型组相比,τ 1、τ 2均显著缩短(p0.01);(4)电压依赖性激活-失活：模型组与假手术组相比半数激活电位降低(p0.01),黄芪组、人参组、党参组、西药组与模型组相比,半数激活电位均显著升高(p0.01)。4.益气药对心衰小鼠L型钙通道及CaMKⅡ表达的干预作用：(1)模型组与假手术组相比CANCA1C (L型钙通道主要亚基)表达水平无统计学差异,各给药组与模型组相比CANCA1C表达水平无统计学差异；(2)模型组与假手术组相比CaMKⅡ蛋白表达水平显著升高(p0.01),黄芪组、人参组、党参组、西药组与模型组相比CaMKⅡ蛋白表达水平均显著降低(p0.01)。结论1.益气药(黄芪+党参)能够缩短心梗后心衰心脏复极时间,但对心梗后心衰模型心功能无明显改善效果；黄芪、人参、党参均能缩短压力负荷致心衰心脏复极时间,改善心衰电生理重构,并且黄芪能够同时改善心脏收缩和舒张功能,党参能够改善心脏收缩功能；2.益气药黄芪、人参、党参能够不同程度地干预心衰细胞L型钙电流密度,失活速度,电压依赖性激活、失活,改善心衰细胞L型钙电流重构,并且缩短心衰细胞动作电位复极时间,干预心衰细胞电生理重构,其中党参、黄芪的干预效果显著；3.益气药黄芪、人参、党参对L型钙通道的调控作用可能是通过抑制CaMKⅡ过表达实现的。
[Abstract]:Heart failure (heart failure (heart failure), heart failure, HF) is an important cardiovascular disease that endangers human health in twenty-first Century. The 5 year survival rate of patients with heart failure is about 50%. The incidence of malignant arrhythmia in D patients with heart failure is significantly increased, and nearly 50% patients die from sudden cardiac sudden death caused by malignant arrhythmia. It is one of the important reasons for the death of the patients with heart failure. Electrophysiological remodeling refers to the changes in the electrical impulse and conduction mechanism of cardiac myocytes in the heart failure, which involves changes in the function of various ion channels and cell signal transduction systems, in which the L type calcium current changes and the action potential time (Acti) On potential duration, APD) is the key link. At present, there is still a lack of effective drugs for electrophysiological remodeling of heart failure for clinical selection. The study of traditional Chinese medicine may be the breakthrough point to solve this problem. Chinese medicine thinks that qi deficiency is the basic pathogenesis of heart failure, which runs through the development of heart failure, and Yiqi medicine is one of the prevention and treatment of heart failure in Chinese medicine. Basic drugs can improve cardiac function and clinical symptoms and improve the quality of life of patients with heart failure. Astragalus membranaceus, Codonopsis and ginseng are commonly used medications in clinical practice. At present, the mechanism of traditional Chinese medicine has the characteristics of multilevel, multi link, multi target and so on. The earlier study has discussed the improvement of Qi and drug from the angle of energy metabolism and sarcoplasmic reticulum calcium transport. The mechanism of cardiac function of heart failure model, but the mechanism of improving the prognosis of heart failure model has not been reported from the angle of electrophysiologic reconstruction. Two mice models of heart failure after coronary artery infarction and coarctation of the aorta caused by the coarctation of the aorta were used in this study. Cell patch clamp technique and Western Blot molecular biology methods have been studied from the whole, cell and molecular level to verify that "Yiqi drugs may inhibit the over expression of calcium / calmodulin dependent protein kinase II (calcium/calmodulin-dependent protein kinase II, CaMKII), regulate the L type calcium current of heart failure cells and shorten the heart failure of cardiac myocytes. The scientific hypothesis of cardiac repolarization time, improving electrophysiological remodeling of heart failure. Method 1. animal model: coronary ligation, aortic coarctation, heart failure after myocardial infarction and pressure load heart failure in two mice; 2. groups and administration: (1) the mice were divided into model group, sham operation group and Qi supplementing group (astragalus + party) after coronary artery ligation. The 4 groups in the western medicine group (Mei TORO M) were given the corresponding drug intervention for 4 weeks after operation; (2) the mice were randomly divided into model group, sham operation group, Huang Qi group (Huang Qi), ginseng group (ginseng), Panax Codonopsis (Codonopsis) group (Codonopsis pilosula) and Western medicine group (Mei TORO M) for 4 weeks after operation, and 3. test methods: (1) 4 weeks after coronary ligation. 4 weeks after the coarctation of the rat and the aorta, the mice were recorded body weight, death and other general conditions. The cardiac contractions, diastolic and ventricular remodeling were detected by the echocardiography of small animals. The incidence of QT interval and ventricular arrhythmia was detected by electrocardiogram. (2) 4 Zhou Xiaoshu acute isolated myocardial cells after coarctation of aorta and full cell diaphragm were used. The clamp technique was used to record the APD of myocardial cells, and the L calcium current density, the inactivation time constant (T) and the voltage dependent activation inactivation curve were recorded by the whole cell voltage forceps mode. (3) the myocardium was taken for 4 weeks after the coarctation of the aorta, and the L calcium channel was detected by Western Blot technique and the protein expression level of CaMKII. The evaluation of 1. heart failure model: (1) the left ventricular ejection fraction (left ventricular ejection fraction, LVEF) in the model mice of the 4 weeks after coronary artery ligation decreased significantly (P0.01), the left ventricular inner diameter increased significantly (P0.01), and the corrected QT interval (QTc) was significantly prolonged (P0.01); (2) the model mice and the artificial hand after the coarctation of the aorta were 4 weeks after the operation. Compared with LVEF (P0.01), left ventricular inner diameter increased (P0.05), left ventricle anterior wall thickness increased significantly (P0.01), Ea significantly decreased (P0.01), QTc significantly prolonged (P0.01) the intervention effect of.2. (P0.01).2. supplementing drug on heart function and QT interval of heart failure mice: (1) 4 weeks after coronary artery ligation, the supplementing Qi group was higher than the model group. Compared with the model group, there was no significant difference in LVEF between the western medicine group and the model group, and the QTc was significantly shorter than the model group (P0.01). (2) at 4 weeks after the coarctation of the aorta, the LVEF increased (P0.05) and the Ea increased significantly (P0.01) compared with the model group, and the LVEF group was significantly higher than the model group (P0.01); the Astragalus group and the ginseng group were significantly higher than the model group. Compared with the model group, QTc significantly shortened the effect of (P0.01).3. supplementing on APD and L type calcium current of heart failure cells: (1) compared with the sham group, APD: model group was significantly longer (P0.01) when the 0.21,2.0Hz frequency stimulated the repolarization of cardiac action potential (APD90), and the astragalus group was compared with the model group in 0.2Hz, 2.0Hz frequency. Myocardial cell APD90 shortened (P0.05) under the rate of rate stimulation. Compared with the model group, the APD90 significantly shortened (P0.01) under the 0.2Hz and 2.0Hz frequency stimulation, and the APD90 shortened (P0.05) compared with the model group under the intervention of isoproterenol (isoprenaline, ISO); (2) ICa, L current density: the model group was compared with the sham operation group. The current density of ICa and L increased significantly (P0.01) under the stimulation of Z, and the current density of L decreased significantly (P0.01) in ICa under 1.0Hz stimulation compared with the model group. Compared with the model group, the group of Codonopsis and Codonopsis were 0.1 Hz, 1.0Hz stimulated ICa, and the L current density decreased. Inactivation time constant: the model group was compared with the sham group ICa, the L rapid inactivation time constant (tau 1) and the slow inactivation time constant (tau 2) were significantly prolonged (P0.01). Compared with the model group, the Astragalus group, the ginseng group and the Codonopsis group were significantly shorter than the model group (P0.01); (4) the voltage dependent activation deactivation: the model group was half activated compared to the sham operation group. Potential decrease (P0.01), Astragalus group, ginseng group, Codonopsis group, and Western medicine group compared with the model group, the median activation potential increased significantly (P0.01) the intervention effect of.4. supplementing drug on L calcium channel and CaMK II expression in heart failure mice: (1) there was no statistical difference between the model group and the sham group CANCA1C (the main subunit of the L type calcium channel), and the difference between the model group and the sham group. There was no significant difference in the level of CANCA1C expression in the drug group compared with the model group. (2) the expression level of CaMK II protein in the model group was significantly higher than that in the sham group (P0.01). The expression level of the CaMK II protein in the Astragalus group, the ginseng group, the Codonopsis group, the western medicine group and the model group were all significantly lower (P0.01). Conclusion the conclusion of the drug (Astragalus membranaceus + Codonopsis) can shorten the myocardial infarction (P0.01). Heart failure repolarization time, but not significantly improved cardiac function after myocardial infarction, astragalus, ginseng, Codonopsis can shorten the heart failure heart repolarization time, improve heart failure electrophysiological reconfiguration, and Astragalus can improve cardiac contractile and diastolic function, Codonopsis can improve cardiac contractile function; 2. Yiqi medicine yellow Radix astragalus, ginseng, and Codonopsis pilosula can interfere with L type calcium current density, inactivation speed, voltage dependent activation, inactivation, reactivation of L type calcium current in heart failure cells, shorten the repolarization time of action potential of heart failure cells, and intervene electrophysiological reconstruction of heart failure cells, among which, the intervention effect of Radix Codonopsis and Astragalus membranaceus is significant; 3. the Astragalus membranaceus (Astragalus membranaceus) Ginseng and Codonopsis pilosula can regulate L type calcium channel by inhibiting CaMK II overexpression.
【学位授予单位】：北京中医药大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R541.6
本文编号：2135578
[Abstract]:Heart failure (heart failure (heart failure), heart failure, HF) is an important cardiovascular disease that endangers human health in twenty-first Century. The 5 year survival rate of patients with heart failure is about 50%. The incidence of malignant arrhythmia in D patients with heart failure is significantly increased, and nearly 50% patients die from sudden cardiac sudden death caused by malignant arrhythmia. It is one of the important reasons for the death of the patients with heart failure. Electrophysiological remodeling refers to the changes in the electrical impulse and conduction mechanism of cardiac myocytes in the heart failure, which involves changes in the function of various ion channels and cell signal transduction systems, in which the L type calcium current changes and the action potential time (Acti) On potential duration, APD) is the key link. At present, there is still a lack of effective drugs for electrophysiological remodeling of heart failure for clinical selection. The study of traditional Chinese medicine may be the breakthrough point to solve this problem. Chinese medicine thinks that qi deficiency is the basic pathogenesis of heart failure, which runs through the development of heart failure, and Yiqi medicine is one of the prevention and treatment of heart failure in Chinese medicine. Basic drugs can improve cardiac function and clinical symptoms and improve the quality of life of patients with heart failure. Astragalus membranaceus, Codonopsis and ginseng are commonly used medications in clinical practice. At present, the mechanism of traditional Chinese medicine has the characteristics of multilevel, multi link, multi target and so on. The earlier study has discussed the improvement of Qi and drug from the angle of energy metabolism and sarcoplasmic reticulum calcium transport. The mechanism of cardiac function of heart failure model, but the mechanism of improving the prognosis of heart failure model has not been reported from the angle of electrophysiologic reconstruction. Two mice models of heart failure after coronary artery infarction and coarctation of the aorta caused by the coarctation of the aorta were used in this study. Cell patch clamp technique and Western Blot molecular biology methods have been studied from the whole, cell and molecular level to verify that "Yiqi drugs may inhibit the over expression of calcium / calmodulin dependent protein kinase II (calcium/calmodulin-dependent protein kinase II, CaMKII), regulate the L type calcium current of heart failure cells and shorten the heart failure of cardiac myocytes. The scientific hypothesis of cardiac repolarization time, improving electrophysiological remodeling of heart failure. Method 1. animal model: coronary ligation, aortic coarctation, heart failure after myocardial infarction and pressure load heart failure in two mice; 2. groups and administration: (1) the mice were divided into model group, sham operation group and Qi supplementing group (astragalus + party) after coronary artery ligation. The 4 groups in the western medicine group (Mei TORO M) were given the corresponding drug intervention for 4 weeks after operation; (2) the mice were randomly divided into model group, sham operation group, Huang Qi group (Huang Qi), ginseng group (ginseng), Panax Codonopsis (Codonopsis) group (Codonopsis pilosula) and Western medicine group (Mei TORO M) for 4 weeks after operation, and 3. test methods: (1) 4 weeks after coronary ligation. 4 weeks after the coarctation of the rat and the aorta, the mice were recorded body weight, death and other general conditions. The cardiac contractions, diastolic and ventricular remodeling were detected by the echocardiography of small animals. The incidence of QT interval and ventricular arrhythmia was detected by electrocardiogram. (2) 4 Zhou Xiaoshu acute isolated myocardial cells after coarctation of aorta and full cell diaphragm were used. The clamp technique was used to record the APD of myocardial cells, and the L calcium current density, the inactivation time constant (T) and the voltage dependent activation inactivation curve were recorded by the whole cell voltage forceps mode. (3) the myocardium was taken for 4 weeks after the coarctation of the aorta, and the L calcium channel was detected by Western Blot technique and the protein expression level of CaMKII. The evaluation of 1. heart failure model: (1) the left ventricular ejection fraction (left ventricular ejection fraction, LVEF) in the model mice of the 4 weeks after coronary artery ligation decreased significantly (P0.01), the left ventricular inner diameter increased significantly (P0.01), and the corrected QT interval (QTc) was significantly prolonged (P0.01); (2) the model mice and the artificial hand after the coarctation of the aorta were 4 weeks after the operation. Compared with LVEF (P0.01), left ventricular inner diameter increased (P0.05), left ventricle anterior wall thickness increased significantly (P0.01), Ea significantly decreased (P0.01), QTc significantly prolonged (P0.01) the intervention effect of.2. (P0.01).2. supplementing drug on heart function and QT interval of heart failure mice: (1) 4 weeks after coronary artery ligation, the supplementing Qi group was higher than the model group. Compared with the model group, there was no significant difference in LVEF between the western medicine group and the model group, and the QTc was significantly shorter than the model group (P0.01). (2) at 4 weeks after the coarctation of the aorta, the LVEF increased (P0.05) and the Ea increased significantly (P0.01) compared with the model group, and the LVEF group was significantly higher than the model group (P0.01); the Astragalus group and the ginseng group were significantly higher than the model group. Compared with the model group, QTc significantly shortened the effect of (P0.01).3. supplementing on APD and L type calcium current of heart failure cells: (1) compared with the sham group, APD: model group was significantly longer (P0.01) when the 0.21,2.0Hz frequency stimulated the repolarization of cardiac action potential (APD90), and the astragalus group was compared with the model group in 0.2Hz, 2.0Hz frequency. Myocardial cell APD90 shortened (P0.05) under the rate of rate stimulation. Compared with the model group, the APD90 significantly shortened (P0.01) under the 0.2Hz and 2.0Hz frequency stimulation, and the APD90 shortened (P0.05) compared with the model group under the intervention of isoproterenol (isoprenaline, ISO); (2) ICa, L current density: the model group was compared with the sham operation group. The current density of ICa and L increased significantly (P0.01) under the stimulation of Z, and the current density of L decreased significantly (P0.01) in ICa under 1.0Hz stimulation compared with the model group. Compared with the model group, the group of Codonopsis and Codonopsis were 0.1 Hz, 1.0Hz stimulated ICa, and the L current density decreased. Inactivation time constant: the model group was compared with the sham group ICa, the L rapid inactivation time constant (tau 1) and the slow inactivation time constant (tau 2) were significantly prolonged (P0.01). Compared with the model group, the Astragalus group, the ginseng group and the Codonopsis group were significantly shorter than the model group (P0.01); (4) the voltage dependent activation deactivation: the model group was half activated compared to the sham operation group. Potential decrease (P0.01), Astragalus group, ginseng group, Codonopsis group, and Western medicine group compared with the model group, the median activation potential increased significantly (P0.01) the intervention effect of.4. supplementing drug on L calcium channel and CaMK II expression in heart failure mice: (1) there was no statistical difference between the model group and the sham group CANCA1C (the main subunit of the L type calcium channel), and the difference between the model group and the sham group. There was no significant difference in the level of CANCA1C expression in the drug group compared with the model group. (2) the expression level of CaMK II protein in the model group was significantly higher than that in the sham group (P0.01). The expression level of the CaMK II protein in the Astragalus group, the ginseng group, the Codonopsis group, the western medicine group and the model group were all significantly lower (P0.01). Conclusion the conclusion of the drug (Astragalus membranaceus + Codonopsis) can shorten the myocardial infarction (P0.01). Heart failure repolarization time, but not significantly improved cardiac function after myocardial infarction, astragalus, ginseng, Codonopsis can shorten the heart failure heart repolarization time, improve heart failure electrophysiological reconfiguration, and Astragalus can improve cardiac contractile and diastolic function, Codonopsis can improve cardiac contractile function; 2. Yiqi medicine yellow Radix astragalus, ginseng, and Codonopsis pilosula can interfere with L type calcium current density, inactivation speed, voltage dependent activation, inactivation, reactivation of L type calcium current in heart failure cells, shorten the repolarization time of action potential of heart failure cells, and intervene electrophysiological reconstruction of heart failure cells, among which, the intervention effect of Radix Codonopsis and Astragalus membranaceus is significant; 3. the Astragalus membranaceus (Astragalus membranaceus) Ginseng and Codonopsis pilosula can regulate L type calcium channel by inhibiting CaMK II overexpression.
【学位授予单位】：北京中医药大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R541.6
【相似文献】
相关期刊论文 前10条
1 黄丽洁,解立新,贾琳,赵晓巍,刘又宁,苟鹏;杂种犬急性呼吸窘迫综合征模型的建立[J];中国比较医学杂志;2004年04期
2 张臣颢;张曼芳;谢青莲;成志恒;邹洪;金玫蕾;;慢性不可预知温和应激抑郁小鼠模型的建立[J];复旦学报(自然科学版);2011年03期
3 谭潇;肖建华;;1型糖尿病小鼠模型的构建[J];国际检验医学杂志;2011年14期
4 任文英,陈香美,邱全瑛,陈扬荣,王新高,师锁柱,王兆霞;慢性移植物抗宿主病狼疮样小鼠模型的诱导[J];中国比较医学杂志;2004年04期
5 王艳春,吕莉;弥散性血管内凝血模型的改进[J];第四军医大学吉林军医学院学报;2005年02期
6 陈小囡;;蜂胶对慢性酒精性肝损伤的保护作用及其机制研究[J];健康研究;2009年02期
7 武君;孙长岗;郑华;;愈宁散对CITP模型小鼠外周血共刺激分子CD86影响的实验研究[J];实用中医内科杂志;2010年09期
8 王紫;陈瑜;罗军;周建华;;槐杞黄干预小鼠IgA肾病模型的疗效观察以及机制探讨[J];中国中西医结合肾病杂志;2011年11期
9 孙旖;夏振娜;袁伯俊;张晓芳;陆国才;;LT-Y008的骨髓保护作用及机制[J];中国药理学与毒理学杂志;2013年03期
10 周厚广,鲍远程,陆建明;提高帕金森病动物模型制作成功率的方法学探讨及模型综合评价[J];国际神经病学神经外科学杂志;2005年04期
相关会议论文 前10条
1 阎明;张喜红;刘莉;孟繁立;张莉;朱萍;;美能对酒精性肝纤维化大鼠的干预及治疗研究[A];第五届全国肝脏疾病临床暨中华肝脏病杂志成立十周年学术会议论文汇编[C];2006年
2 王勇炫;吴伟康;吴以岭;张选红;;蜈蚣有效部位抗心肌缺血的NO机制研究[A];2009年全国中药学术研讨会论文集[C];2009年
3 周友龙;李建生;高剑峰;;老龄大鼠脑缺血再灌注微血管再生的变化意义[A];中国中西医结合学会第五届基础理论研究专业委员会学术研讨会论文集[C];2006年
4 赵万军;周辉;韩勇;何永江;;丹参对激素性股骨头坏死血管内凝血的影响[A];2007年浙江省医学会骨科学学术会议暨浙江省抗癌协会骨软肿瘤学术会议论文汇编[C];2007年
5 孙元莹;史晓峰;;益肺康颗粒对油酸致兔急性肺损伤实验研究[A];2003年全国危重病急救医学学术会议论文集[C];2003年
6 孙元莹;史晓峰;;益肺康颗粒对油酸致兔急性肺损伤实验研究[A];2004年全国危重病急救医学学术会议论文集[C];2004年
7 李玉中;;复方甘正对非酒精性脂肪性肝炎的治疗作用[A];第五次全国中青年检验医学学术会议论文汇编[C];2006年
8 孙旖;夏振娜;袁伯俊;张晓芳;陆国才;;LT-Y008的骨髓保护作用及机制[A];2013年（第三届）中国药物毒理学年会暨药物非临床安全性评价研究论坛论文摘要[C];2013年
9 孙旖;夏振娜;袁伯俊;张晓芳;陆国才;;LT-Y008的骨髓保护作用及机制[A];中国药理学与毒理学杂志(2013年6月第27卷第3期)[C];2013年
10 罗道枢;王玮;;细胞外信号调节激酶在三叉神经痛动物模型中的活化[A];2007年中国解剖学会第十届全国组织学与胚胎学青年学术研讨会论文摘要汇编[C];2007年
相关重要报纸文章 前1条
1 武汉市中西医结合医院 单萍;黄角颗粒抗脑梗死作用机理[N];中国中医药报;2007年
相关博士学位论文 前10条
1 沈斌;肝豆灵对铜负荷大鼠肝组织的miRNA-122和代谢组学的影响[D];湖北中医药大学;2015年
2 赵宾宾;地五养肝胶囊抑制2-AAF/PH大鼠肝癌前病变的作用及机制[D];湖北中医药大学;2015年
3 李思耐;基于L型钙电流研究益气药干预心衰电生理重构机制[D];北京中医药大学;2016年
4 乌日图那顺;蒙药“伊赫汤”对酒精性脂肪肝作用机理的实验研究[D];北京中医药大学;2015年
5 胡文军;复方脑康胶囊治疗Alzheimer's病的药效学研究[D];南方医科大学;2012年
6 王涛;普利醇抗帕金森病的药效学及其机制研究[D];中国协和医科大学;2009年
7 张志慧;老年性痴呆脑微血管发病机制及通心络干预研究[D];河北医科大学;2010年
8 程静;从津液代谢角度探讨肺与大肠相表里的理论和实验研究[D];湖北中医药大学;2010年
9 张军芳;芪苈强心胶囊对心力衰竭微血管损伤、心室重构及代谢重构的影响[D];河北医科大学;2013年
10 侯燕;冠状动脉粥样硬化模型猪胆固醇代谢异常对Aβ的影响及复方干预研究[D];辽宁中医药大学;2015年
相关硕士学位论文 前10条
1 张子洋;醒脑液对APPswe/PS1ΔE9双转基因小鼠脑内Aβ及其降解酶NEP表达的影响[D];河北联合大学;2014年
2 韩金丽;急性胰腺炎大鼠神经降压素水平与肠黏膜损伤关系的实验研究[D];河北医科大学;2015年
3 潘彩彬;膝关节炎治疗仪对膝骨性关节炎软骨形态及关节液细胞因子影响的实验研究[D];福建中医药大学;2015年
4 浦飞飞;敬钊缨毛蜘蛛毒素-V对LTP和认知行为改善作用的分子机制研究[D];北京协和医学院;2015年
5 崔庆飞;酒精联合高脂饮食诱导小鼠脂肪肝模型的建立及发病机制探讨[D];河北医科大学;2015年
6 刘翠华;谷氨酰胺对脓毒症小鼠氧化应激作用效果的研究[D];河北医科大学;2015年
7 岳萌;Bufalin通过ERK/RSK2通路对ECA109细胞和裸鼠移植瘤作用的研究[D];河北医科大学;2015年
8 左玲;Xyloketal B对NAFLD的疗效观察和机制研究[D];暨南大学;2015年
9 郎艳松;通心络联合阿托伐他汀、阿司匹林对新西兰兔动脉粥样硬化早期颈动脉外膜滋养血管新生相关炎症机制的影响[D];河北医科大学;2015年
10 赵祥梅;结直肠炎相关结直肠肿瘤模型的建立与机制初步探讨[D];广西医科大学;2015年
，本文编号：2135578
本文链接：https://www.wllwen.com/yixuelunwen/xxg/2135578.html
最近更新
教材专著
