依普利酮抑制急性心肌梗死大鼠心肌纤维化的作用机制

［］目的 观察依普利酮对急性心肌梗死大鼠心肌中转化生长因子β1(TGF-β1)及心肌纤维化的影响。方法 将结扎左冠状动脉致急性心肌梗死大鼠模型,随机分为急性心肌梗死组和依普利酮治疗组,假手术组为仅打开心包腔而未行冠状动脉结扎大鼠。分别用依普利酮(30mg.kg-1.d-1)和等量生理盐水灌胃4周。心肌Masson染色法测定心肌胶原密度,测算心肌胶原容积分数(CVF)和血管周围胶原面积(PVCA);碱水解法测定羟脯氨酸(Hyp)含量;放射免疫法检测心肌醛固酮(Ald)含量;Western-blot检测心肌TGF-β1表达。 结果 (1)急性心梗组大鼠心肌组织中CVF、PVCA、Hyp较假手术组显著增加(P ＜0.01),心肌Ald、TGF-β1表达显著升高,(P ＜0.01)。(2) 依普利酮治疗组大鼠心肌中CVF、PVCA、Hyp较急性心梗组显著降低(P ＜0.01),心肌TGF-β1表达显著减低(P ＜0.05)。 结论 抑制急性心肌梗死大鼠心肌组织中TGF-β1表达,这可能是依普利酮抑制心肌纤维化的机制之一。     

心脏肥大细胞在自发性高血压大鼠心肌重构中的作用

目的探讨心脏肥大细胞在自发性高血压大鼠(SHR)心肌重构中的作用。方法应用病理检查、计算机分析结合逆转录聚合酶链式反应等方法,观察SHR及Wistar-Kyoto大鼠(WKY)收缩压、左室重量指数、心肌细胞直径、肥大细胞密度、心肌胶原容积分数(CVF)、心肌血管周围胶原面积比(PV-CA)和心肌Ⅰ、Ⅲ型胶原mRNA表达水平的变化。肥大细胞密度与左室重量指数、CVF及PVCA之间的关系采用相关分析。结果与WKY比较,SHR收缩压为(206±18)比(108±10)mm Hg(P<0.01);SHR组左室重量指数为(4.6±0.4)比(3.3±0.3)mg/g,(P<0.01);SHR组心肌细胞长径为(17.4±1.9)比(10.0±2.2)μm(P<0.01);SHR组心肌细胞短径为(9.0±2.0)比(5.8±1.7)μm(P<0.01);SHR组肥大细胞密度为(7.4±3.2)比(1.9±1.2)个/mm2(P<0.01),SHR组肥大细胞密度为WKY组的3.9倍。SHR组CVF、PVCA分别为46.4%±7.8%和1.9±0.9,WKY组分别为24.4%±10.7%和0.4±0.1,SHR组明显升高(P<0.01)。SHR组心肌Ⅰ、Ⅲ型胶原mRNA表达相对含量也均明显高于WKY(P<0.01),心脏肥大细胞密度与左室重量指数、CVF及PVCA存在明显的正相关(相关系数分别为0.67、0.87和0.95,P<0.01)。结论心脏肥大细胞密度增加可能是促进SHR心肌重构的重要原因。     

熊果酸在大鼠自体静脉移植再狭窄模型中抑制血管炎症因子的实验研究

目的 探讨熊果酸对大鼠自体静脉再狭窄过程中炎症反应的抑制作用及可能的机制。方法 SD大鼠45只，体重300～350 g，随机分成A组、B组和C组，每组15只。A组大鼠不做任何处理，B组和C组大鼠用“套管法”将其右侧颈外静脉移植至右侧颈总动脉，C组术后每天予以熊果酸30 mg?kg-1?d-1灌胃。术后48 h切除右侧颈外静脉检测MCP-1、IL-1α、IL-6和 TNF-α等细胞因子。结果 MCP-1（A组655.5±47.4，B组7959.7±823.5，C组4339.0±578.8，pg/mg），IL-1α（A组496.8±46.2，B组4015.6±427.1，C组2838.5±298.9，pg/mg），IL-6（A组664.4±63.5，B组2414.8±155.1，C组1325.8±56.4，pg/mg），TNF-α（A组149.5±7.8，B组546.0±72.6，C组286.2±18.6，pg/mg）。B组和C组细胞因子均较A组显著增高，且差异具有统计学意义。C组细胞因子较B组显著降低，且差异具有统计学意义。结论 熊果酸可能通过抑制炎症反应中心物质NF-κB的活化，进而抑制MCP-1、IL-1α，IL-6及TNF-α的表达。熊果酸可以抑制术后静脉桥血管的再狭窄。     

大鼠急性心肌梗死后心脏炎症细胞因子基因和蛋白表达及辛伐他汀干预研究

目的探讨辛伐他汀对急性心肌梗死(AMI)后大鼠心脏炎症细胞因子肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)和白细胞介素-10(IL-10)mRNA表达和蛋白质产生的影响。方法Wistar大鼠36只分3组:(1)假手术(Sham)组;(2)心肌梗死对照(MI-C)组;(3)辛伐他汀(MI-S)组。动物笼养4周取出心脏,沿乳头肌等分为二,一半用逆转录聚合酶链反应法测定心脏细胞因子mRNA表达,另一半用Western blot测定细胞因子蛋白质生成量。结果Sham组上述细胞因子均无明显表达,MI-C组TNF-α,IL-1β,IL-6和IL-10 mRNA和蛋白产生均显著高于Sham组;同MI-C组比较,MI-S组的TNF-α,IL-1β,IL-6 mRNA和蛋白生成均显著下降,而IL-10的mRNA和蛋白明显升高。结论辛伐他汀明显降低AMI后大鼠心脏的致炎症细胞因子,而升高炎症保护因子IL-10。     

心脏肥大细胞在自发性高血压大鼠心肌重构中的作用

目的探讨心脏肥大细胞在自发性高血压大鼠(SHR)心肌重构中的作用.方法应用病理检查、计算机分析结合逆转录-聚合酶链式反应等方法,观察SHR及Wistar-Kyoto大鼠(WKY)收缩压、左室重量指数、心肌细胞直径、肥大细胞密度、心肌胶原容积分数(CVF)、心肌血管周围胶原面积比(PV-CA)和心肌Ⅰ、Ⅲ型胶原mRNA表达水平的变化.肥大细胞密度与左室重量指数、CVF及PVCA之间的关系采用相关分析.结果与WKY比较,SHR收缩压为(206±18)比(108±10)mm Hg(P<0.01);SHR组左室重量指数为(4.6±0.4)比(3.3±0.3)mg/g,(P<0.01);SHR组心肌细胞长径为(17.4±1.9)比(10.0±2.2)μm(P<0.01);SHR组心肌细胞短径为(9.0±2.0)比(5.8±1.7)μm(P<0.01);SHR组肥大细胞密度为(7.4±3.2)比(1.9±1.2)个/mm2(P<0.01),SHR组肥大细胞密度为WKY组的3.9倍.SHR组CVF、PVCA分别为46.4%±7.8%和1.9±0.9,WKY组分别为24.4%±10.7%和0.4±0.1,SHR组明显升高(P<0.01).SHR组心肌Ⅰ、Ⅲ型胶原mRNA表达相对含量也均明显高于WKY(P<0.01),心脏肥大细胞密度与左室重量指数、CVF及PVCA存在明显的正相关(相关系数分别为0.67、0.87和0.95,P<0.01).结论心脏肥大细胞密度增加可能是促进SHR心肌重构的重要原因.     

吡非尼酮通过调节急性心肌梗死大鼠TGF-β1/Smad通路改善心室重构

摘要 目的：探讨吡非尼酮调节急性心肌梗死大鼠TGF-β1/Smad通路对心室重构的影响。方法：将72只SD大鼠随机分为假手术组、模型组、吡非尼酮低剂量组（50mg/kg）、吡非尼酮中剂量组(100mg/kg)、吡非尼酮高剂量组(200mg/kg)、福辛普利组（阳性对照组,15mg/kg）,每组12只。除假手术组外,其余各组大鼠制备急性心肌梗死模型,药物处理组大鼠每天灌胃治疗,假手术组及模型组大鼠以同剂量生理盐水灌胃,持续14d,给药结束24h后,检测大鼠左心室质量指数;伊红（HE）、天狼星红染色分别检测大鼠心肌组织病理形态变化及心室纤维化程度;酶联免疫吸附法（ELISA）检测各组大鼠血清中肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、转化生长因子β（TGF-β1)水平;免疫印迹实验（Western blot）检测各组大鼠心肌组织TGF-β1/Smad通路蛋白的表达情况。结果：与假手术组比较,模型组大鼠心肌组织形态改变明显,呈现心肌细胞肥大、坏死,心肌纤维扭曲、断裂,炎性细胞浸润等病理损伤,并有大量胶原沉积,呈现纤维化变性,左心室质量指数增大、血清TNF-α、IL-6及TGF-β1水平、心肌组织TGF-β1表达及p-Smad/Smad明显升高（P均＜0.05）。吡非尼酮低、中、高剂量组、福辛普利组大鼠病理损伤及纤维化程度较模型组轻,左心室质量指数、血清TNF-α、IL-6及TGF-β1水平、心肌组织TGF-β1表达及p-Smad/Smad较模型组降低,且吡非尼酮各组呈剂量依赖性（P均＜0.05）;吡非尼酮高剂量组与福辛普利组比较,差异无统计学意义（P>0.05）。结论：吡非尼酮可抑制心肌梗死大鼠心肌炎症,降低病理损伤及纤维化变性,改善心室重构,可能是通过下调TGF-β1/Smad通路实现的。     

PCBP2在压力负荷诱导的小鼠心肌肥厚发生中的作用

目的 探讨PCBP2在压力负荷诱导的小鼠心肌肥厚发生过程中的作用。方法 选取8～10周龄的雄性C57BL/6小鼠20只,体重23～28 g;随机分为2组,每组各10只,分别施以主动脉缩窄术（TAC组）和假手术（Sham组）。术后4周应用超声心动图评价小鼠的心脏功能,应用心脏重量与体重之比（HW/BW）定量评价心肌肥厚程度。Real-time PCR检测心肌肥厚标志物Nppa、β-MHC（Myh7）的mRNA水平,同时检测PCBP2 mRNA水平。Western blot方法检测Nppa、β-MHC及PCBP2的蛋白水平。比较分析两组之间的差异。结果 与Sham组相比,TAC组小鼠的心肌肥厚程度明显增加（TAC组 vs Sham组=8.23±1.88 mg/g vs 4.89±0.68 mg/g）,左心室射血分数（TAC组 vs Sham组=59.15±3.58% vs 41.38±2.22%）及短轴收缩率（TAC组 vs Sham组=43.87±1.37% vs 33.61±0.92%）明显降低（P<0.05）。TAC组的心肌肥厚标志物Nppa、β-MHC 的mRNA水平及蛋白水平均明显高于Sham组（P<0.05）。然而,TAC组PCBP2 mRNA水平及蛋白水平却明显低于Sham组（P<0.05）,与心肌标志物Nppa、β-MHC的变化趋势相反。结论 PCBP2在压力负荷诱导的小鼠心肌肥厚发生过程中起着负性调节作用,上调PCBP2表达可能会抑制心肌肥厚的发展。     

肾去交感支配对心肌梗死后大鼠心肌纤维化和转化生长因子-β1的影响

目的 探讨肾去交感神经术(Renal sympathetic denervation,RSD)对心肌梗死大鼠心肌纤维化和转化生长因子-β1(TGF-β1)表达水平的影响。方法 52只雄性SD大鼠随机分为4组,正常组对照组（Control组）、肾去交感组（RSD组）、心肌梗死组(MI7d Sham组)、肾去交感干预组（MI7d RSD组）。MI7d Sham组和MI7d RSD组分别给予前降支冠脉结扎术制备心梗模型7天后行肾交感假手术或去交感术。心脏彩超评估大鼠左心室收缩末期直径（LVESD）,左心室射血分数（LVEF）和左心室短轴缩短率（LVFS）。Masson法检测大鼠左心室心肌胶原容积分数(CVF)。RT-PCR法和Western-blot法分别检测大鼠左室心肌TGF-β1 mRNA和TGF-β1蛋白的相对表达水平。结果 与MI7d Sham组相比,MI7d RSD组大鼠LVESD明显减小（LVESD: 3.13mm ± 0.25mm vs. 5.23mm ± 0.15mm, P<0．01）,而LVFS和LVEF均增高（LVFS: (38.2 ± 4.5)% vs. (23.1 ± 3.3)%,P<0．01; LVEF: (61.7 ± 1.3)% vs. (40.4 ± 2.7)%,P<0．01）。与MI7d Sham组相比,MI7d RSD组胶原容积分数减少((42.66 ± 7.55) % vs. (59.33±9.79)%,P<0．01),TGF-β1 mRNA(1.47±0.09 vs. 2.00±0.09,P<0.01)和TGF-β1蛋白(0.46±0.04 vs. 0.73±0.02,P<0．01)的相对表达量均减少。结论 肾去交感神经术能抑制心肌梗死大鼠心肌纤维化并改善心功能,可能与下调TGF-β1的表达有关。     

心肌肥厚患者心脏肥大细胞的改变及意义

目的:探讨心脏肥大细胞在人心肌肥厚、心肌重构中的作用。方法:应用病理检查、计算机分析和逆转录-聚合酶链式反应等方法,观察右心室肥厚患者(心肌肥厚组)和正常人(对照组)心脏肥大细胞密度、心肌细胞横径、心肌间质胶原容积分数(CVF)和心肌血管周围胶原面积比(PVCA)和心肌Ⅰ、Ⅲ型胶原mRNA表达。肥大细胞密度与心肌细胞横径、CVF及PVCA之间的关系采用相关分析。结果:心肌肥厚组心脏肥大细胞密度为(4·7±2·1)个/mm2,对照组为(1·6±1·0)个/mm2,心肌肥厚组心脏肥大细胞密度为对照组的2·9倍(P<0·01)。心肌肥厚组心室肌细胞横径为(15·2±2·7)μm,对照组为(10·5±2·0)μm,与对照组比较,心肌肥厚组明显增加(P<0·01)。心肌肥厚组CVF为(39·5±9·8)%,对照组为(20·9±8·2)%,心肌肥厚组明显升高(P<0·01);心肌肥厚组PVCA为1·98±1·05,对照组为0·41±0·12,心肌肥厚组也明显增加(P<0·01)。心肌肥厚患者心肌Ⅰ、Ⅲ型胶原mRNA表达相对含量也均明显高于正常人(P<0·01),心脏肥大细胞密度与心肌细胞横径、CVF及PVCA存在明显的正相关(相关系数分别为0·73,0·55和0·67,P<0·05或P<0·01)。结论:心脏肥大细胞密度增加有可能促进心肌重构。     

依普利酮对鸟苷酸环化酶偶联受体A基因敲除小鼠心肌纤维化的作用

背景 鸟苷酸环化酶偶联受体A(GC-A)为心钠素(ANP)和脑钠素(BNP)的共有受体,ANP和BNP通过与GC-A结合引起利尿、利钠及扩血管作用,并可抑制肾素和醛固酮分泌,GC-A基因敲除小鼠表现为高血压、心室肥厚和心肌纤维化.目的 探讨高选择性醛固酮受体拮抗剂依普利酮对鸟苷酸环化酶偶联受体A基因敲除(GC-A-KO)小鼠心肌纤维化的作用.方法 12周龄GC-A-KO雄性小鼠21只分成对照组(n=7)、依普利酮组[e-KO组,n=7,100 mg/(kg·d)×4周]和肼苯哒嗪组[h-KO组,n=7,10 mg/(kg·d)×4周],另有野生型(WT)小鼠7只用于测定血压、心率及组织学分析.小鼠于16周龄时处死,计算心脏与体质量比值(HW/BW);利用图像分析系统测量心肌胶原容积分数(CVF)和心肌血管周围胶原面积和管腔面积之比(PVCA);半定量RT-PCR法检测心室胶原纤维Ⅰ和胶原纤维Ⅲ mRNA在心肌组织表达.结果 依普利酮组和肼苯哒嗪组收缩压较对照组明显降低[分别为(103.2±4.2)和(99.6±6.2)vs(130.6±9.2)mm Hg,P均＜0.01];依普利酮组的HW/BW为(4.7±0.3)mg/g低于对照组(5.9±0.5)mg/g(P＜0.05),而肼苯哒嗪组HW/BW为(6.8±0.3)mg/g高于对照组(P＜0.05);与对照组比较,依普利酮组的CVF、PVCA及胶原纤维Ⅰ和胶原纤维Ⅲ mRNA的表达下降(P＜0.01、0.05和0.05),纤维化程度减轻;肼苯哒嗪组尽管血压下降程度与依普利酮组相似,但CVF、PVCA及胶原纤维Ⅰ和胶原纤维Ⅲ mRNA的表达均增加(P均＜0.05),纤维化程度加重.结论 依普利酮可独立于血压改善心肌纤维化和心室重构.     

The cardiac component of cardiac cachexia

Background Recent evidence suggests the importance of noncardiac mechanisms in the genesis of the syndrome of cardiac cachexia. This raises the question of the relative role of the heart itself in this syndrome. This study sought to assess the cardiac dimensions, mass, and function and changes in these parameters over time in patients with chronic heart failure with and without cachexia. Methods Doppler echocardiography was performed in 28 patients with nonedematous weight loss (>7.5% over a period of >6 months) compared with 56 matched patients without weight loss in a ratio of 1:2 (age 71 ± 13 vs 67 ± 8 years, P = .07; New York Heart Association class 2.9 ± 0.7 vs 2.6 ± 0.6, P = .08). In 18 cachectic and 35 noncachectic patients with previous echocardiographic recordings, we analyzed the changes in left ventricular (LV) dimensions and mass over time. Results Cardiac dimensions including LV diastolic (69 ± 9 mm vs 67 ± 13 mm) and systolic cavity diameter (58 ± 11 mm vs 55 ± 15 mm), LV mass (480 ± 180 g vs 495 ± 190 g), and LV systolic and diastolic function including fractional shortening (16% ± 10% vs 18% ± 10%), isovolumic relaxation time (29 ± 22 ms vs 36 ± 27 ms), and E/A ratio (2.7 ± 1.6 vs 3.3 ± 2.9) did not differ between cachectic and noncachectic patients (all P > .1). By analyzing changes in LV mass over time, we found an increase (>20%) in 2 (11%) cachectic and 14 (40%) noncachectic patients and a decrease in LV mass (>20%) in 9 (50%) cachectic and 8 (23%) noncachectic patients (χ² test, P < .05). Conclusions Although no specific cardiac abnormality could be detected echocardiographically in cachectic patients compared with patients with noncachectic chronic heart failure in a cross-sectional study, over time a significant loss of LV mass (>20%) occurs more frequently in patients with cardiac cachexia. (Am Heart J 2002;144:45-50.)     

心脏骤停和心脏性猝死

心脏性猝死(SCD)是目前社会关注的热点问题.2005年WHO的数据表明,在全球死于心脑血管疾病的约1700万人群中,40%～50%是SCD.SCD虽然有多种定义,但目前一般认为是在1 h内出现的由于心血管原因导致的非预期死亡事件或无目击者的死亡事件.心脏骤停(SCA)不等同于SCD,SCA如果救治失败会引起真正的SCD.     

Sodium-induced cardiac aldosterone synthesis causes cardiac hypertrophy

High sodium intake causes cardiac hypertrophy independently of increases in blood pressure. Aldosterone is synthesized in extraadrenal tissues such as blood vessels, brain, and heart. Effects of 8 weeks of high sodium intake on cardiac aldosterone synthesis, as well as cardiac structure, mass, and aldosterone production, levels of mRNA coding for aldosterone synthase (CYP11B2) and the angiotensin II AT1 receptor, were studied in normotensive Wistar-Kyoto (WKY) rats. Isolated rat hearts were perfused for 2 hr, and the perfusate was analyzed by high-performance liquid chromatography and mass spectrometry. Aldosterone synthase activity was estimated from the conversion of [14C]deoxycorticosterone to [14C]aldosterone. Levels of mRNA for CYP11B2 and AT1 receptor were determined by competitive polymerase chain reactions. A high sodium intake for 8 weeks produced left ventricular hypertrophy without elevation of blood pressure. Plasma aldosterone concentrations and plasma renin concentrations were decreased by high sodium intake. Aldosterone production, activity of aldosterone synthase, and expression of mRNA for CYP11B2 and AT1 receptor were increased in hearts of rats with high sodium intake. These results suggest that high sodium intake increases cardiac aldosterone synthesis, which may contribute to cardiac hypertrophy independently of the circulating renin-angiotensin-aldosterone system.     

Analysis of cardiac symptoms preceding cardiac arrest

Prodromal symptoms and cardiac history were examined in 227 patients with coronary artery disease who were successfully resuscitated after out-of-hospital cardiac arrest. Cardiac arrest was sudden—with either no symptoms or symptoms for less than 1 hour—in 71% of the patients. Nonsudden death—death occurring after more than 1 hour of symptoms—occurred in 29% of the patients. A history of cardiovascular disease was present in 85% of patients with sudden cardiac arrest and in 83% with nonsudden arrest. Cardiac arrest occurred without symptoms in 38% of the patients with sudden cardiac arrest and was the first expression of coronary artery disease in 4% of the entire study group. This study indicates that cardiac arrest usually occurs with symptoms and almost always in the setting of a history of cardiovascular disease.     

Occult cardiac lymphoma presenting with cardiac tamponade

Subxiphoid pericardiostomy is the procedure of choice for treatment of a pericardial effusion with tamponade. We report a case in which this procedure not only failed to reveal the presence of an occult malignancy, but also resulted in a recurrent symptomatic effusion.     

External cardiac pacing during in-hospital cardiac arrest

External noninvasive cardiac pacing offers a rapid and simple method of pacing the heart during an emergency. It has been suggested that early use of cardiac pacing for bradycardia or asystole may improve survival in patients who have cardiac arrest. To investigate this possibility 58 consecutive episodes of cardiac arrest occurring on the medical wards or emergency room. Twenty-six episodes underwent external noninvasive pacing for bradycardia or asystole refractory to standard drugs. Only 2 patients survived, and survival could be directly attributed to pacing in only 1 of them. Of the 32 episodes not undergoing pacing, 23 had transient asystole or bradycardia, 13 of which rapidly responded to medications. The 17 cases (53%) not undergoing pacing survived. In conclusion, when bradycardia or asystole during cardiac arrest fails to respond to standard pharmacologic measures, it is an indicator of severe myocardial damage, and attempts at cardiac pacing rarely improve survival.     

Acute cardiac tamponade due to cardiac actinomycosis

Cardiac actinomycosis occurs in less than 2 percent of the patients with infections due to Actinomyces israelii. We describe the findings in a patient with acute cardiac tamponade who survived through pericardial drainage and aggressive medical therapy. Although uncommon, this disorder is important to recognize because it is curable with current medical and surgical therapy.     

Noninvasive transcutaneous cardiac pacing in prehospital cardiac arrest

This study evaluated the efficacy of prehospital external cardiac pacing in cardiac arrest patients. From October 1984 to June 1985, 91 patients were paced. Mean time from cardiac arrest to advanced life support (ALS) intervention in this metropolitan-rural ALS system was 14.5 minutes. Electrical capture occurred in 85 (93%), mechanical capture (pulses) occurred in ten (11%), and a measurable blood pressure occurred in three (3%) of the 91 patients. Despite a high rate of electrical capture, palpable pulses were produced only in 11%, and no patients survived to be discharged from the hospital. There was no difference in the frequency of electrical capture, palpable pulses, or outcome for patients receiving pharmacologic intervention before or after pacing. Likewise there was no difference in the frequency of electrical capture, palpable pulses, or outcome for patients receiving ALS therapy within or after ten minutes of their arrest. Although we found that external cardiac pacing was easily used in the prehospital setting, pacing did not result in any increase in survival in cardiac arrest patients.