碱性成纤维细胞生长因子诱导老年大鼠心肌细胞保护及其机制研究

目的　探讨碱性成纤维细胞生长因子（bFGF）对老年大鼠心肌细胞缺氧/复氧（H/R）损伤的影响及其保护机制。　方法　在分离的老年大鼠心肌细胞H/R模型上,观察bFGF预孵育对H/R后心肌细胞乳酸脱氢酶（LDH）漏出、ATP含量和细胞存活率的影响,并采用滤纸法测定心肌细胞外信号调节激酶(ERKs)活性的变化。　结果　bFGF激活ERKs,并呈剂量依赖性减轻H/R所致心肌细胞损伤,表现为细胞存活率〔bFGF10ng组(70.0±4.6)%,H/R组(53.0±4.5)%,P＜0.01〕和细胞内ATP含量〔bFGF10ng组(23.1±2.3)nmol/106细胞,H/R组(12.3±2.1)nmol/106细胞,P＜0.01〕升高,细胞浆酶LDH漏出〔bFGF10ng组（257.3±51.0）U/L,H/R组（372.5±69.2）U/L,P＜0.05〕减少;ERKs上游激酶抑制剂PD098059完全消除上述保护作用〔PD098059组细胞存活率（57.0±5.8）%,ATP含量（15.1±2.6）nmol/106细胞,培养液中LDH活性（325.5±59.0）U/L,与bFGF10ng组比较均为P＜0.01〕。　结论　bFGF可以提高老年大鼠心肌细胞对于缺氧的耐受性,其保护机制涉及ERKs的活化。     

急性心肌梗死后心肌细胞凋亡的研究进展

研究表明，急性心肌梗死(AMI)后，凋亡可致心肌细胞数量减少，影响心肌梗死面积。心室重构中，凋亡也可能是决定AMI向心力衰竭转归快慢的因素之一。     

急性心肌梗死后心室重塑--心肌细胞凋亡的意义

急性心肌梗死 (AMI)后的心室重塑是指心肌梗死后心室大小、形态、结构和功能的变化过程 ,包括 :梗死区心肌坏死产生膨出、非梗死区心肌肥大、间质纤维化、心室壁增厚扩张并导致整个心室的进行性扩张、变形和收缩功能降低。近年来研究发现 ,心肌细胞凋亡也是导致心肌细胞数量减少的重要原因 ,在心室重塑中起重要作用 ,本文将就这方面的研究进展进行综述。细胞凋亡的基本概念　　细胞凋亡又称程序性细胞死亡 ,是由基因控制的细胞主动死亡形式。其主要特征为细胞皱缩、细胞膜完整并发泡、细胞器完整、染色质固缩和凋亡小体形成。细胞凋亡在正…     

miRNA调控心肌梗死后心肌细胞凋亡的研究进展

miRNA是长度为21～23个核苷酸的非编码单链RNA小分子，可调节目标mRNA的稳定性和转录的效率，参与调控心肌梗死(MI)后心肌细胞凋亡的分子机制。成熟心肌细胞不可再生的特殊性，决定了抑制心肌细胞凋亡是治疗心血管疾病的重要突破口。本文依据miRNA转录后抑制多种心肌细胞的mRNA生物学特性，综述了miRNA与心肌细胞凋亡通路的关系，阐明miRNA在调控MI后心肌细胞凋亡的分子网络中的作用，为今后心血管疾病的诊治提供新思路和方法。     

曲尼司特对急性心肌梗死大鼠心肌细胞凋亡的影响

曲尼司特是一种过敏介质阻滞剂，最初主要应用于变态反应疾病和皮肤病的治疗。近来研究表明，它在心力衰竭的治疗中起一定作用，能够降低急性心肌梗死（AMI）大鼠心肌肥大细胞数和肥大细胞蛋白酶-1（rat mast cell protease-1，RMCP-1）mRNA的表达，改善AMI大鼠心脏的收缩和舒张功能。研究表明，曲尼司特可能是通过抑制肥大细胞脱颗粒和RMCP-1的合成，进而阻止心力衰竭的发生发展的。体外实验证实，肥大细胞颗粒能引起心肌细胞凋亡，且这种作用主要由RMCP-1介导。因此，抑制心肌细胞凋亡可能是曲尼司特改善心功能，阻止心力衰竭发生发展的机制之一。     

黄芪多糖对大鼠缺氧/复氧诱导的心肌细胞自噬及凋亡抑制作用的机制探讨

目的：探究黄芪多糖（APS）通过调控高迁移率族蛋白1/Toll样受体4/核转录因子-κB(HMGB1/TLR4/NF-κB)信号通路对大鼠缺氧/复氧（H/R）诱导的心肌细胞自噬及凋亡的抑制作用。方法：建立H9C2心肌细胞H/R损伤模型并分为4组：对照组、H/R组、APS组和HMGB1抑制剂组。CCK-8法和EdU染色法检测细胞增殖能力;酶联免疫吸附试验检测细胞肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1β、IL-6含量;透射电镜观察细胞自噬小体的形成;膜联蛋白V-异硫氰酸荧光素/碘化丙啶（AnnexinV-FITC/PI）双染法检测细胞凋亡;实时定量PCR检测细胞HMGB1、TLR4、NF-κB p65 mRNA表达水平;蛋白免疫印迹法检测细胞HMGB1、TLR4、NF-κB p65、B细胞淋巴瘤-2(Bcl-2)、Bcl-2相关X蛋白（Bax）、含半胱氨酸的天冬氨酸蛋白水解酶-3(caspase-3)、P62、微管相关蛋白1A/1B-轻链3(MAP1LC3,缩写为LC3)-Ⅱ蛋白表达水平。结果：与对照组相比,H/R组细胞增殖能力明显减弱,凋亡及自噬水平明显增加,细胞内可见大量自...     

阿托伐他汀对大鼠急性心肌梗死后心肌细胞凋亡的影响

将60只雄性Wistar大鼠随机分为假手术组10只和急性心肌梗死（AMI）组50只。AMI组通过结扎左冠状动脉前降支制作AMI模型,成功后24h剩余36只,再随机分为AMI对照组和干预组各18只。干预组每日予阿托伐他汀（40mg／kg）灌胃,假手术组和AMI对照组每日予等量生理盐水灌胃。4周后分别采用TUNEL法和RT-PCR法检测非梗死区心肌细胞凋亡指数（MAI）和TNF-α mRNA的表达水平。结果干预组和AMI对照组非梗死区心肌中MAI和TNF-α mRNA的表达均明显高于假手术组（P〈均〈0．05）,干预组与AMI对照组相比上述指标均明显降低（P均〈0．05）。提示阿托伐他汀可降低大鼠AMI后非梗死区MAI,抑制非梗死区心肌中TNF-α mRNA的表达可能是其机制之一。     

急性心肌梗死后心肌细胞凋亡的研究进展

研究表明,急性心肌梗死(AMI)后,凋亡可致心肌细胞数量减少,影响心肌梗死面积.心室重构中,凋亡也可能是决定AMI向心力衰竭转归快慢的因素之一.     

他汀类药物抗心肌细胞凋亡机制

近来实验证实他汀类药物具有除降血脂以外的心肌保护效应。现主要从他汀类药物激活磷脂酰肌醇-3激酶丝氨酸- 苏氨酸激酶／一氧化氮舍酶(PI3K／Akt／eNOS)信号通路、抑制氧化应激和抑制糖原合成激酶3β(GSK3β)三个方面阐述他汀类药物抑制心肌细胞凋亡的主要机制。     

再灌注损伤对大鼠心肌细胞凋亡的影响

目的 一定时间的心肌缺血可诱导心肌细胞凋亡,而缺血后再灌注损伤对心肌细胞凋亡影响尚未阐明.方法 将50只SD大鼠随机分为5组,以TUNEL分析和超微病理学检测各组心肌组织的细胞凋亡情况.结果 TUNEL检测发现再灌注各组缺血区心肌均出现阳性反应的心肌细胞,透射电镜发现了具有凋亡形态学特征的心肌细胞.随再灌注时间延长,心肌细胞凋亡指数显著增加(P<0.05),而单纯缺血无上述发现.结论 再灌注直接导致了缺血后的心肌细胞凋亡,细胞凋亡是再灌注导致的迟发性心肌细胞死亡的一种方式.     

Effects of ivabradine on cardiomyocyte apoptosis after rabbit acute myocardial infarction

Epidemiological studies have confirmed that high heart rate means high risk to patients with coronary heart disease.The research investigates the viability and the effects of ivabradine versus atenolol in early phases of acute myocardial infarction(AMI) on rabbits after 28 days of follow-up.The ratio of bcl-2 protein to Bax protein determines survival or death after an apoptotic stimulus.We forecast that bcl-2 or Bax expression places a premium on ischemia and that it may be linked to myocyte death in human hearts.Methods Forty-three New Zealand white rabbits(male or female) were used to build AMI mode through ligating left anterior descending coronary artery.Survived rabbis were randomly divided into four groups:group S,group M,group A and group I.Drugs were provided 12 hours post myocardial infarction induction.The myocardium in ischemic necrosis tissue was sampled 28 days post dose.AI and bcl-2 /bax protein expression were detected.The heart rates of rabbits before operation and 28 days after operation were recorded by electrocardiography and analyzed.Results On 28th day post-operation,the heart rate of rabbits in groups A and I significantly became slower compared with that in group M(P < 0.01).The proportion of myocardial cell apoptosis in groups I and A was significantly lower than that in group M and higher than that in group S(P < 0.01) on 28th day post-operation On 28th day post-operation,compared with group M,the level of Bcl2 protein in rabbits of groups I and A significantly increased(P < 0.01),the level of Bax protein significantly decreased(P < 0.01),and No statistical difference was found between group I and group A.Conclusion reating myocardial infarction rabbits with ivabradine for 28 days could effectively reduce the incidence of myocardial cell apoptosis and increase bcl-2 /bax ratio.     

阿托伐他汀早期干预对急性心肌梗死心肌细胞凋亡的影响

目的探讨不同剂量阿托伐他汀提早干预治疗,对兔急性心肌梗死(AMI)细胞凋亡的影响。方法24只新西兰兔随机分为3组:①对照组:不予药物干预;②低剂量组:0.5mg·kg-1·d-1阿托伐他汀;③高剂量组:5mg·kg-1·d-1阿托伐他汀。在药物干预3d后制作AMI模型,检测心肌梗死及其边缘区细胞凋亡率并观察心肌Bax和Bcl-2表达。结果①高剂量组心肌细胞凋亡率明显低于对照组和低剂量组(P<0.05,P<0.01)。②高剂量组Bcl-2表达高于对照组及低剂量组(P<0.01,P<0.05),对照组与低剂量组差异无统计学意义;三组Bax表达均较高,但组间比较,差异无统计学意义。③Pearson线性相关分析显示梗死及其边缘区心肌细胞凋亡率与相应区域Bcl-2表达呈负相关,与心肌组织Bax表达无明显相关关系。结论高剂量阿托伐他汀降低梗死区及其边缘区心肌细胞凋亡率,与低剂量相比显示出更好保护作用。     

Sustained cardiomyocyte apoptosis and left ventricular remodelling after myocardial infarction in experimental diabetes

Aims/hypothesis Diabetes is known to reduce survival after myocardial infarction. Our aim was to examine whether diabetes is associated with enhanced cardiomyocyte apoptosis and thus interferes with the post-infarction remodelling process in myocardium in rat.Methods Four weeks after intravenous streptozotocin (diabetic groups) or citrate buffer (controls) injection, myocardial infarction was produced by ligation of left descending coronary artery. Level of cardiomyocyte apoptosis was quantified by TUNEL and caspase-3 methods. Collagen volume fraction and connective tissue growth factor were determined under microscope. Left ventricular dimensions were evaluated by echocardiography and planimetry.Results The number of apoptotic cardiomyocytes was equally high in diabetic and non-diabetic rats after 1 week from infarction. At 12 weeks after infarction the number of apoptotic cells was higher in the diabetic as compared to non-diabetic rats both in the border zone of infarction and in non-infarcted area. Correspondingly, left ventricular end diastolic diameter, relative cardiac weight, connective tissue growth factor-expression and fibrosis were increased in diabetic compared with non-diabetic rats with myocardial infarction.Conclusion/interpretation Sustained cardiomyocyte apoptosis, left ventricular enlargement, increased cardiac fibrosis and enhanced profibrogenic connective tissue growth factor expression were detected after myocardial infarction in experimental diabetes. Apoptotic myocyte loss could be an important mechanism contributing to progressive dilatation of the heart and poor prognosis after myocardial infarction in diabetes.Abbreviations STZ streptozotozin - MI myocardial infarction - CTGF connective tissue growth factor - LV left ventricular - LVEDD LV end-diastolic diameter - BNP B-type natriuretic peptide     

Effect of metoprolol on myocardial apoptosis and caspase-9 activation after coronary microembolization in rats

OBJECTIVE:

To explore the effect of metoprolol on myocardial apoptosis and caspase-9 activation after coronary microembolization (CME) in rats.

METHODS:

Forty rats were randomly divided into four groups (n=10 each): a sham operation (control) group, CME plus saline (CME) group, CME plus metoprolol (metoprolol) group and caspase-9 inhibitor Z-LEHD-FMK (ZLF) group. CME was induced by injecting 3000 polyethylene microspheres (42 μm diameter) into the left ventricle during a 10 s occlusion of the ascending aorta. Echocardiography, terminal deoxynucleotidyl transferase dUTP nick end labelling and Western blotting were used to evaluate cardiac function, apoptosis and activation of caspase-9/caspase-3, respectively, 6 h after CME.

RESULTS:

The echocardiographic parameters of left ventricular function were significantly decreased in the CME group compared with the control group (P<0.05); however, the metoprolol group and ZLF group showed significantly improved cardiac function compared with CME alone (P<0.05). Compared with the control group, the myocardial apoptosis rate and the levels of activated caspase-9 and -3 increased significantly in the CME group (P<0.05). Again, these effects were ameliorated by metoprolol and ZLF (P<0.05).

CONCLUSIONS:

The present study demonstrates that metoprolol and ZLF can protect the rat myocardium during CME by inhibiting apoptosis and improving cardiac function, likely by inhibiting apoptosis/ mitochondrial apoptotic pathway. These results suggest that antiapoptotic therapies may be useful in treating CME.     

血管内皮生长因子对急性心肌梗死大鼠心肌细胞凋亡的影响

目的　探讨静脉应用血管内皮生长因子 (VEGF)对急性心肌梗死大鼠心肌细胞凋亡及凋亡相关蛋白P5 3、Fas、Bax和Bcl 2表达的影响。　方法　 3 3只雄性SD大鼠结扎左冠状动脉后 2 4h随机接受VEGF16 5 肝素 (治疗组 )或肝素 生理盐水 (对照组 )治疗。VEGF16 5(2 μg/1ml)加肝素 (5 0U)或肝素 生理盐水 (5 0U/1ml)每天经尾静脉注射 ,共用 7d(治疗组 8只 ,对照组 10只 )和 14d(治疗组 7只 ,对照组 8只 )。于结扎后第 9天和第 16天测定心肌细胞凋亡指数、心肌组织P5 3、Fas、Bax和Bcl 2蛋白的表达。　结果　治疗组的心肌细胞凋亡数量明显少于对照组〔第 9天 :(10± 2 ) %比 (2 8±2 ) % ,P <0 0 1;第 16天 :(6± 2 ) %比 (12± 2 ) % ,P <0 0 5〕 ,VEGF抑制P5 3、Fas和Bax的表达 ,促进Bcl 2的表达。　结论　每天静脉应用VEGF 14d可减少心肌细胞凋亡 ,抑制P5 3、Fas和Bax的表达 ,促进Bcl 2的表达     

川芎嗪注射液通过激活Notch通路抑制心肌梗死大鼠心肌细胞增殖、凋亡与坏死的作用研究

目的 探讨川芎嗪注射液通过激活Notch通路抑制心肌梗死大鼠心肌细胞增殖、凋亡与坏死的作用.方法 SD雄性大鼠随机分为3组,模型组、干预组及对照组.模型组、干预组于冠状动脉(冠脉)左前降支进行结扎以构建急性心肌梗死大鼠模型,对照组只进行穿线不结扎.建模24 h后干预组腹腔注射120 mg/kg川芎嗪注射液,1/d,连续...     

氧化槐定碱通过Nrf2/HO-1通路抑制大鼠急性心肌梗死后心肌细胞凋亡

目的观察氧化槐定碱(OSR)通过核因子E2相关因子2(Nrf2)/血红素氧化酶1(HO-1)通路抑制大鼠急性心肌梗死(AMI)后心肌细胞凋亡的作用。方法成年健康雄性SD大鼠分为假手术组、AMI组、OSR组、OSR+锌原卟啉9(ZPP-Ⅸ)组,后3组采用左冠状动脉前降支结扎的方式建立AMI模型,OSR组给予OSR腹腔注射,OSR+ZPP-Ⅸ组给予OSR及HO-1抑制剂ZPP-Ⅸ腹腔注射。检测血清心肌酶含量、心肌细胞凋亡率、心肌中凋亡基因及Nrf2、HO-1的表达量。结果 AMI组大鼠的血清乳酸脱氢酶(LDH)、磷酸肌酸激酶(CK)、磷酸肌酸激酶同工酶(CK-MB)含量、心肌细胞凋亡率以及心肌中Bcl-2相关X蛋白(Bax)、Cleaved-caspase-3、Nrf2、HO-1的表达量均明显高于假手术组,心肌中B淋巴细胞瘤2蛋白(Bcl-2)的表达量明显低于假手术组。OSR组大鼠的血清LDH、CK、CK-MB含量、心肌细胞凋亡率以及心肌中Bax、Cleaved-caspase-3的表达量均明显低于AMI组,心肌中Bcl-2、Nrf2、HO-1的表达量明显高于AMI组。OSR+ZPP-Ⅸ组大鼠的血清LDH、CK、CK-MB含量、心肌细胞凋亡率以及心肌中Bax、Cleaved-caspase-3的表达量均明显高于OSR组,心肌中Bcl-2的表达量明显低于OSR组。结论OSR通过激活Nrf2/HO-1通路抑制大鼠AMI后心肌细胞的凋亡。     

抑郁对急性心肌梗死大鼠心室重构的影响及其机制探讨

Objective To observe the effect of depressive disorder on ventricular remodeling and its mechanism in acute myocardial infarction (AMI) rats. Methods Forty-six AMI Wistar rats were randomly divided into sham-operation (n=10), AMI (n=12), depression (n=12), neurostan by open field test, and the detection of angiotensin Ⅱ (Ag Ⅱ ), aldosterone (ALD), malondialdehyde (MDA), superoxide dismutase (SOD) were performed, the pathological sections were observed under light and electron microscopes. Results Compared with sham-operation group, depression group had decreased values of squares crossing times, rearing times and grooming time, increased time of staying in the central square and defecation. Compared with depression group, AMI and neurostan treatment groups had increased values of squares crossing times, rearing times and grooming time,decreased time of staying in the central square and defecation (F=16. 9, 44.56, 71.79, 34.86,29. 18, P＜0.01). At the 4 week of test, the left and right ventricular relative weights (LVRW,RVRW) and thickness of interventricular septum were (1.63±0.15) mg/g, (0. 48±0. 10) mg/g and (1.75 ± 0. 38) mm in sham-operation group, the corresponding data were (2.06±0.21) mg/g,(0.62±0.10) mg/g and (2.25±0.30) mm in AMI group, (2.90±0.47) mg/g, (1.00±0.28) mg/gand (2.58±0.34) mm in depression group, (2.20±0.34) mg/g, (0.67±0.15) mg/g and (2. 25±0.23) mm in neurostan treatment group. Compared with sham-operation group, AMI, depression and neurostan groups had obviously increased values of LVRW, RVRW and thickness of interventricular septum. Compared with depression group, AMI and neurostan groups had decreased LVRW, RVRW and thickness of interventricular septum (F=6.31, 21.9, 115.7, 9.91, P＜0.05). And the depression also could aggravate edema and injury of ultrastructure in myocardial tissue. The values of AgⅡ , ALD, MDA and SOD were (1957.5±662.6) ng/L, (0.453±0.111) ng/L, (16. 00±3.03)nmol/L and (80.57 ± 7.00) U/ml in depression group, the corresponding data were (1143.8± 98.0)ng/L, (0.198±0.087) ng/L, (8.03 ± 0.44 ) nmol/L and (95.20 ± 4.87) U/ml in sham-operated group, (1407.5±255.8) ng/L, (0.295±0.027) ng/L, (11.18±4.30) nmol/L and (87.33±3.51)U/ml in AMI group, (1400.0±239.0) ng/L, (0.326±0.073) ng/L, (11.88±3.36) nmol/L and (89.13 ±0.17) U/ml in neurostan group. After 4 weeks, the values of Ag Ⅱ , ALD and MDA increased in depression group while the level of SOD reduced (F=6.58, 11.9, 11.39, 8. 82, P＜0.05). Conclusions Depressive disorder after AMI in rats can aggravate ventricular remodeling and lower the ability of antioxygen.     

抑郁对急性心肌梗死大鼠心室重构的影响及其机制探讨

目的 观察抑郁对急性心肌梗死大鼠心室重构及抗氧化能力的影响. 方法 实验大鼠46只,随机分为4组:假手术组(10只),梗死模型组(12只)、抑郁模型组(12只)、路优泰组(12只).路优泰组给予每天路优泰90mg/kg给药4周后用Open-field法观察各组大鼠行为学变化以及测定血管紧张素Ⅱ(AgⅡ)、醛固酮、丙二醛(MDA)、超氧化物歧化酶(SOD)值和光镜、电镜下观察心肌组织切片. 结果 与假手术组比较,抑郁模型组水平穿越格数、竖立次数、理毛时间均减少,中央格停留时间、粪便粒数均增加;与抑郁模型组比较,梗死模型型组、路优泰组水平穿越格数、竖立次数、理毛时间明显增加,中央格停留时间、粪便粒数明显减少(F值分别为16.9、44.56、71.79、34.86、29.18,均P＜0.01).实验第4周各组大鼠左室相对重量、右室相对重量、室间隔厚度假手术组分别为(1.63±0.15)mg/g、(0.48±0.10)mg/g、(1.75±0.38)mm,梗死模型组分别为(2.06±0.21)mg/g、(0.62±0.10)mg/g、(2.25±0.30)mm,抑郁模型组分别为(2.90±0.47)mg/g、(1.00±0.28)mg/g、(2.58±0.34)mm,路优泰组分别为(2.20±0.34)mg/g、(0.67±0.15)mg/g、(2.25±0.23)mm,与假手术组比较,梗死模型组、抑郁模型组、路优泰组,左室相对重量、右室相对重量、室间隔厚度明显增加,与抑郁模型组比较,梗死模型组、路优泰组左室相对重量、右室相对重量、室间隔厚度减少(F值分别为6.31、21.9、115.7、9.19,均P＜0.05).并且抑郁可加重心肌水肿及超微结构损伤.实验第4周AgⅡ、醛固酮、丙二醛、SOD值,抑郁组大鼠分别为(1957.5±662.6)ng/L、(0.453±0.111)ng/L(16.00±3.03)nmol/L、(80.57±7.00)U/ml,假手术组大鼠分别为(1143.8±98.0)ng/L、(0.198±0.087)ng/L、(8.03±0.44)nmol/L、(95.20±4.87)U/ml,梗死模型组大鼠分别为(1407.5±255.8)ng/L、(0.295±0.027)ng/L、(11.18±4.30)nmol/L、(87.33±3.51)U/ml,路优泰组(1400.0±239.0)ng/L、(0.326±0.073)ng/L、(11.88±3.36)nmol/L、(89.13±0.17)U/ml,抑郁组大鼠4周后,AgⅡ、醛固酮、丙二醛数值明显高于各组,而SOD值低于各组(F值分别为6.58、11.9、11.39、8.82,P＜0.05). 结论 心肌梗死后抑郁可加重大鼠急性心肌梗死后心室重构及降低机体抗氧化能力.