泻肺利水法治疗慢性心力衰竭及对内质网应激影响研究
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摘要
临床研究
目的：观察泻肺利水法治疗心力衰竭的临床效果及其对心肌细胞内质网应激相关凋亡因子的影响。方法：研究对象为2011年4月-2012年12月于首都医科大学附属北京中医医院及平谷区中医医院住院诊断为CHF的患者。实验随机分为对照组(35例)及治疗组(35例)。对CHF患者首先进行辨证分型,治疗组在常规治疗的基础上加用泻肺利水法组方的汤药。入院后及治疗两周后应用超声心动图测LVEF及LVED,并测定患者的血清中细胞凋亡相关因子sFas/Apo-1、sFasL含量及血清NT-proBNP。结果：治疗后治疗组症状、体征积分低于对照组,差异有统计学意义(P<0.05)；治疗组与对照组治疗后NT-proBNP下降、LVEF上升、LVED下降,治疗组NT-proBNP下降与LVEF升高较对照组明显(P<0.05)；两组治疗后血清中sFas/Apo-1、sFasL含量较治疗前均显著降低(P<0.01)；治疗组sFas/Apo-1及sFasL水平较对照组明显降低(P<0.05)。结论：泻肺利水法能够有效改善心衰患者的临床症状,降低患者脑钠肽水平,提高LVEF值,降低LVED,改善患者心功能,可下调心肌细胞的凋亡因子sFas及sFasL的水平,抑制心肌细胞的凋亡
基础研究
目的：观察泻肺利水法组方的心衰2号对小鼠体外心肌细胞肥大模型细胞凋亡的影响。方法：培养大鼠乳鼠原代心肌细胞,建立AngII诱导的肥大心肌细胞模型。实验分为7组,即正常对照组、模型组、5%空白血清组、5%心衰2号含药血清组(5%含药血清组)、10%空白血清组、10%心衰2号含药血清组(10%含药血清组)、卡托普利组。采用形态学和免疫细胞化学两种方法分别鉴定心肌细胞；通过图像处理软件测算心肌细胞面积；台盼兰拒染法检测细胞活力；Hoechst33342染色检测心肌细胞的早期凋亡率；Western-blot(?)去检测Grp78、caspase-12、JNK、CHOP蛋白的表达水平。结果：心肌细胞鉴定显示心肌细胞阳性率≥95%,保证了实验结果的真实性和可靠性。①模型组心肌细胞较正常对照组细胞面积明显增大(P<0.05)；细胞活力下降(P<0.05);凋亡率显著提高(P<0.01)；Grp78、caspase-12、JNK、CHOP蛋白表达水平明显上调(P<0.01)。②与5%空白血清组相比,5%含药血清组未能防止心肌细胞肥大；但可提高细胞活力(P<0.05),心肌细胞早期凋亡率显著降低(P<0.01)。③与10%空白血清组相比,10%含药血清组可抑制心肌细胞肥大的发生(P<0.05)；心肌细胞活力虽有所提高但无统计学意义(P>0.05)；心肌细胞早期凋亡率显著降低(P<0.01)；可以显著下调Grp78、caspase-12、CHOP蛋白表达水平(P<0.01),并降低JNK的表达(P<0.05)④10%含药血清组与5%含药血清组相比,10%含药血清组抑制细胞肥大(P<0.05),细胞活力略有升高,但无统计学差异(P>0.05);细胞早期凋亡率显著降低(P<0.01)。结论：①经心衰2号含药血清干预的肥大细胞可有效抑制细胞肥大,提高细胞活力,降低细胞早期凋亡率,减少LDH的释放。②与5%含药血清组相比,10%含药血清组更能防止细胞肥大,降低凋亡率及LDH释放,提示泻肺利水法组方的心衰2号可能具有最佳剂量,降低药物浓度将会影响其保护作用。③心衰2号可以下调内质网应激相关蛋白Grp78、caspase-12、JNK及CHOP的表达水平,提示心衰2号通过减轻内质网应激防止细胞发生凋亡,保护心肌细胞。
Clinical research
Objective:To observe the clinical effects in the treatment of heart fai lure patients and the effects on myocardial cell endoplasmic reticulum stress-related apoptosis factors by XinShuaiErHao which eliminating Pathogens from the Lung and Diuresis. Methods:Research object is CHF inpatients in Beijing Hospital of Traditional Chinese Medicine and Pinggu district hospital of traditional Chinese medicine between2011.4to2012.12. They were divided randomly into two groups, the control group (35cases) and the treatment group (35cases).Firstly, CHF patients were clsssified by differente symptoms and signs, based on routine therapy the treatment group combined with Chinese medicine which was formed under the guidance of eliminating Pathogens from the Lung and Diuresis. LVEF, LVED were detected by echocardiographic before and after2two weeks therapy, and test the level of apoptosis-related factors sFas/Apo-1, sFasL and NT-proBNP level content in serum. Result:After treatment, the symptoms and physical signs of the treatment group were lower than the control group, the difference was statistically significant (P<0.05); after treatment, the NT-proBNP decreased, LVEF increased, LVED decreased in the two groups, while the NT-proBNP and LVEF increased of the treatment group decreased significantly compared with the control group (P<0.05); after treatment the serum sFas/Apo-1, sFasL content of the two groups were significantly decreased than before treatment (P<0.01); the sFas/Apo-1and sFasL levels were significantly lower in the treatment group than that in the control group (P<0.05). Conclusion:XieFeiLiShui can effectively improve the clinical symptoms of patients with heart failure, reduced the level of brain natriuretic peptide in patients, enhanced the value of the LVEF, reduced LVED, improve the cardiac function of CHF patients. And also can down-regulate the apoptosis related factor sFas and sFasL levels of myocardial cells so as to inhibite myocardial apoptosis.
Basic research
Objective:To observe the effects of XinShuaiErHao which eliminating Pathogens from the Lung and Diuresis cell apoptosis on the hypertrophy of myocardial of mice in vitro model. Methods:Cultured primary neonatal rat myocardial cells, established hypertrophic myocardial model by AngⅡ, Experiment were divided into7groups:control group, model group,5%blank serum group,5%XinShuaiErHao group,10%blank serum group,10%XinShuaiErHao group, and captopril group. Use morphological and immunocytochemical methods to identify of myocardial cells. Calculated myocardial cell area by image processing software. Compared cell viability among the groups of myocardial by typan-blue exclusion assays. Compared myocytes early apoptosis rate by Hoeehst33342staining method. Us ing Western blot to detected protein expression of Grp78, caspase-12, JNK and CHOP. Result:Identification of myocardial cells showed myocytes positive rate≥95%, ensured the veracity and reliability of this experiment.①Comparing with the control group, the cell area of model group increases markedly(P<0.05), the survival rate of myocardial cells reduced (P<0.05). Early apoptosis rate of myocardial cells increased significant ly (P<0.01). Grp78、caspase-12、JNK and CHOP proteins were over-expressed.②5%XinShuaiErHao group can not prevent hypertrophy of Myocardial cell compared with5%black serum group, though survival rate of5%XinShuaiErHao group is higher than that of5%control group (P<0.05), and early apoptosis rate and the of5%XinShuaiErHao group decline (P<0.01).③Comparing with the10%black serum group,10%XinShuaiErHao group has the effect of inhibiting the hypertrophy (P<0.05). Although the survival rate of myocardial cells has improved, No significant difference were found between two groups.10%XinShuaiErHao group's early apoptosis rate (P<0.01) were lower than10%black serum group. Besides that, the expression level of Grp78、caspase-12、CHOPwere down-regulated (P<0.01), JNK protein level decreased (P<0.05) compared with10%black serum group.④Between10%XinShuaiErHao group and5%XinShuaiErHao group,10%XinShuaiErHao group can preventing cardiac myocyte hypertrophy (P<0.05), the survival rate of10%XinShuaiErHao group is higher than that of5%XinShuaiErHao group, but the difference was not statistically significant (P>0.05), the early apoptosis rate of myocardial cells was lower markedly (P<0.01), and release rate of LDH declined (P<0.05). Conclusion:①Cardiac myocytes which intervention by XinShuaiErHao can improve the hypertrophic cells survival and reduce the rate of early apoptotic.②Comparing with the5%XinShuaiErHao group,10%XinShuaiErHao group can preventing cardiac myocyte hypertrophy, reducing the rate of early apoptotic and elease rate of LDH, prompting that there may be the best dose for XinShuaiErHao in clinic, if reducing the density of the medicine, efficacy could be worse.③XinShuaiErHao can down-regulated the level of Endoplasmic reticulum stress associated protein: Grp78、caspase-12、JNK and CHOP, which suggest that XinShuaiErHao can protect cardiac myocyte maybe through alleviate Endoplasmic reticulum stress.
目的：观察泻肺利水法治疗心力衰竭的临床效果及其对心肌细胞内质网应激相关凋亡因子的影响。方法：研究对象为2011年4月-2012年12月于首都医科大学附属北京中医医院及平谷区中医医院住院诊断为CHF的患者。实验随机分为对照组(35例)及治疗组(35例)。对CHF患者首先进行辨证分型,治疗组在常规治疗的基础上加用泻肺利水法组方的汤药。入院后及治疗两周后应用超声心动图测LVEF及LVED,并测定患者的血清中细胞凋亡相关因子sFas/Apo-1、sFasL含量及血清NT-proBNP。结果：治疗后治疗组症状、体征积分低于对照组,差异有统计学意义(P<0.05)；治疗组与对照组治疗后NT-proBNP下降、LVEF上升、LVED下降,治疗组NT-proBNP下降与LVEF升高较对照组明显(P<0.05)；两组治疗后血清中sFas/Apo-1、sFasL含量较治疗前均显著降低(P<0.01)；治疗组sFas/Apo-1及sFasL水平较对照组明显降低(P<0.05)。结论：泻肺利水法能够有效改善心衰患者的临床症状,降低患者脑钠肽水平,提高LVEF值,降低LVED,改善患者心功能,可下调心肌细胞的凋亡因子sFas及sFasL的水平,抑制心肌细胞的凋亡
基础研究
目的：观察泻肺利水法组方的心衰2号对小鼠体外心肌细胞肥大模型细胞凋亡的影响。方法：培养大鼠乳鼠原代心肌细胞,建立AngII诱导的肥大心肌细胞模型。实验分为7组,即正常对照组、模型组、5%空白血清组、5%心衰2号含药血清组(5%含药血清组)、10%空白血清组、10%心衰2号含药血清组(10%含药血清组)、卡托普利组。采用形态学和免疫细胞化学两种方法分别鉴定心肌细胞；通过图像处理软件测算心肌细胞面积；台盼兰拒染法检测细胞活力；Hoechst33342染色检测心肌细胞的早期凋亡率；Western-blot(?)去检测Grp78、caspase-12、JNK、CHOP蛋白的表达水平。结果：心肌细胞鉴定显示心肌细胞阳性率≥95%,保证了实验结果的真实性和可靠性。①模型组心肌细胞较正常对照组细胞面积明显增大(P<0.05)；细胞活力下降(P<0.05);凋亡率显著提高(P<0.01)；Grp78、caspase-12、JNK、CHOP蛋白表达水平明显上调(P<0.01)。②与5%空白血清组相比,5%含药血清组未能防止心肌细胞肥大；但可提高细胞活力(P<0.05),心肌细胞早期凋亡率显著降低(P<0.01)。③与10%空白血清组相比,10%含药血清组可抑制心肌细胞肥大的发生(P<0.05)；心肌细胞活力虽有所提高但无统计学意义(P>0.05)；心肌细胞早期凋亡率显著降低(P<0.01)；可以显著下调Grp78、caspase-12、CHOP蛋白表达水平(P<0.01),并降低JNK的表达(P<0.05)④10%含药血清组与5%含药血清组相比,10%含药血清组抑制细胞肥大(P<0.05),细胞活力略有升高,但无统计学差异(P>0.05);细胞早期凋亡率显著降低(P<0.01)。结论：①经心衰2号含药血清干预的肥大细胞可有效抑制细胞肥大,提高细胞活力,降低细胞早期凋亡率,减少LDH的释放。②与5%含药血清组相比,10%含药血清组更能防止细胞肥大,降低凋亡率及LDH释放,提示泻肺利水法组方的心衰2号可能具有最佳剂量,降低药物浓度将会影响其保护作用。③心衰2号可以下调内质网应激相关蛋白Grp78、caspase-12、JNK及CHOP的表达水平,提示心衰2号通过减轻内质网应激防止细胞发生凋亡,保护心肌细胞。
Clinical research
Objective:To observe the clinical effects in the treatment of heart fai lure patients and the effects on myocardial cell endoplasmic reticulum stress-related apoptosis factors by XinShuaiErHao which eliminating Pathogens from the Lung and Diuresis. Methods:Research object is CHF inpatients in Beijing Hospital of Traditional Chinese Medicine and Pinggu district hospital of traditional Chinese medicine between2011.4to2012.12. They were divided randomly into two groups, the control group (35cases) and the treatment group (35cases).Firstly, CHF patients were clsssified by differente symptoms and signs, based on routine therapy the treatment group combined with Chinese medicine which was formed under the guidance of eliminating Pathogens from the Lung and Diuresis. LVEF, LVED were detected by echocardiographic before and after2two weeks therapy, and test the level of apoptosis-related factors sFas/Apo-1, sFasL and NT-proBNP level content in serum. Result:After treatment, the symptoms and physical signs of the treatment group were lower than the control group, the difference was statistically significant (P<0.05); after treatment, the NT-proBNP decreased, LVEF increased, LVED decreased in the two groups, while the NT-proBNP and LVEF increased of the treatment group decreased significantly compared with the control group (P<0.05); after treatment the serum sFas/Apo-1, sFasL content of the two groups were significantly decreased than before treatment (P<0.01); the sFas/Apo-1and sFasL levels were significantly lower in the treatment group than that in the control group (P<0.05). Conclusion:XieFeiLiShui can effectively improve the clinical symptoms of patients with heart failure, reduced the level of brain natriuretic peptide in patients, enhanced the value of the LVEF, reduced LVED, improve the cardiac function of CHF patients. And also can down-regulate the apoptosis related factor sFas and sFasL levels of myocardial cells so as to inhibite myocardial apoptosis.
Basic research
Objective:To observe the effects of XinShuaiErHao which eliminating Pathogens from the Lung and Diuresis cell apoptosis on the hypertrophy of myocardial of mice in vitro model. Methods:Cultured primary neonatal rat myocardial cells, established hypertrophic myocardial model by AngⅡ, Experiment were divided into7groups:control group, model group,5%blank serum group,5%XinShuaiErHao group,10%blank serum group,10%XinShuaiErHao group, and captopril group. Use morphological and immunocytochemical methods to identify of myocardial cells. Calculated myocardial cell area by image processing software. Compared cell viability among the groups of myocardial by typan-blue exclusion assays. Compared myocytes early apoptosis rate by Hoeehst33342staining method. Us ing Western blot to detected protein expression of Grp78, caspase-12, JNK and CHOP. Result:Identification of myocardial cells showed myocytes positive rate≥95%, ensured the veracity and reliability of this experiment.①Comparing with the control group, the cell area of model group increases markedly(P<0.05), the survival rate of myocardial cells reduced (P<0.05). Early apoptosis rate of myocardial cells increased significant ly (P<0.01). Grp78、caspase-12、JNK and CHOP proteins were over-expressed.②5%XinShuaiErHao group can not prevent hypertrophy of Myocardial cell compared with5%black serum group, though survival rate of5%XinShuaiErHao group is higher than that of5%control group (P<0.05), and early apoptosis rate and the of5%XinShuaiErHao group decline (P<0.01).③Comparing with the10%black serum group,10%XinShuaiErHao group has the effect of inhibiting the hypertrophy (P<0.05). Although the survival rate of myocardial cells has improved, No significant difference were found between two groups.10%XinShuaiErHao group's early apoptosis rate (P<0.01) were lower than10%black serum group. Besides that, the expression level of Grp78、caspase-12、CHOPwere down-regulated (P<0.01), JNK protein level decreased (P<0.05) compared with10%black serum group.④Between10%XinShuaiErHao group and5%XinShuaiErHao group,10%XinShuaiErHao group can preventing cardiac myocyte hypertrophy (P<0.05), the survival rate of10%XinShuaiErHao group is higher than that of5%XinShuaiErHao group, but the difference was not statistically significant (P>0.05), the early apoptosis rate of myocardial cells was lower markedly (P<0.01), and release rate of LDH declined (P<0.05). Conclusion:①Cardiac myocytes which intervention by XinShuaiErHao can improve the hypertrophic cells survival and reduce the rate of early apoptotic.②Comparing with the5%XinShuaiErHao group,10%XinShuaiErHao group can preventing cardiac myocyte hypertrophy, reducing the rate of early apoptotic and elease rate of LDH, prompting that there may be the best dose for XinShuaiErHao in clinic, if reducing the density of the medicine, efficacy could be worse.③XinShuaiErHao can down-regulated the level of Endoplasmic reticulum stress associated protein: Grp78、caspase-12、JNK and CHOP, which suggest that XinShuaiErHao can protect cardiac myocyte maybe through alleviate Endoplasmic reticulum stress.
引文
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