左西孟旦对大鼠急性心肌梗死后心肌纤维化及心功能的影响

目的 探讨左西孟旦对心肌梗死（myocardial infarction,MI）大鼠心肌纤维化的影响及其作用机制。 方法 通过结扎大鼠左冠状动脉前降支建立MI模型。30只存活的MI大鼠随机分为模型组和左西孟旦组（Levo组）,每组15只。假手术组（n=10）的大鼠接受相同的外科手术,只是不进行动脉结扎。Levo组胃灌注左西孟旦4.67 μg·kg-1·d-1治疗28 d。假手术组和模型组大鼠同时给等量蒸馏水。采用二维超声心动图评价心功能,Masson-trichrome评价心肌纤维化程度,RT-qPCR检测COL1A1、COL3A1基因表达,Western blot检测SIRT1/TGF-β1/Smad3信号通路蛋白表达。 结果 超声心动图测量显示,与模型组相比,Levo组大鼠的左室收缩末期内径降低（P<0.05）,而射血分数和缩短分数显著升高（P<0.01）。Masson-trichrome显示,左西孟旦治疗可显著减少坏死心肌组织、抑制炎性细胞的浸润并减少胶原蛋白沉积。RT-qPCR分析显示,左西孟旦治疗显著降低了MI大鼠心肌组织中Ⅰ型和Ⅲ型胶原的含量（P<0.01）。Western blot检测显示,左西孟旦治疗可显著上调MI大鼠心肌组织中SIRT1蛋白表达（P<0.01）,下调TGF-β1和p-Smad3蛋白表达（P<0.01）。 结论 左西孟旦具有抗纤维化和心保护作用。这些作用可能通过SIRT1/TGF-β1/Smad3信号通路介导。     

睾酮对大鼠心肌梗塞后心肌肥大的影响

本文应用立体形态定量技术,观察睾酮(T)对心肌梗塞后心肌肥大的影响。实验分为:假手术组(S组)、心肌梗塞组(MI组)。心肌梗塞后睾酮治疗组(MIT组)。结果证明,与S组相比,MI及MIT组大鼠心肌细胞核密度明显减少,尤其以MIT组变化显著,MIT组平均核长度明显增加;MI组的 dp/dt max明显降低,T值延长,MIT组的上两指标无显著差异。MI后血浆T总浓度与平均每核心肌细胞体积呈显著正相关关系。提示:睾酮确实促进了MI后心肌肥大,从而促进了心功能的恢复。     

心脏糜酶活性改变在心肌肥厚患者心肌纤维化中的意义

目的： 观察心脏糜酶与心肌肥厚患者心肌组织胶原合成和心肌纤维化的关系。方法: 应用病理检查、放射免疫、计算机分析和逆转录-聚合酶链式反应等方法，检测心肌肥厚患者（心肌肥厚组）和正常人（对照组）心脏糜酶活性、心肌局部血管紧张素II（Ang II）水平、心肌胶原容积分数（CVF）、心肌血管周围胶原面积比（PVCA）及心肌组织I型和III型胶原mRNA表达。心脏糜酶活性和心肌局部Ang II水平与CVF及PVCA之间的关系采用相关分析。结果: 心肌肥厚组心脏糜酶活性为(0.27±0.06) kU/g蛋白，对照组为(0.12±0.06) kU/g蛋白，心肌肥厚组心脏糜酶活性明显高于对照组（P<0.01）。心肌肥厚组心肌组织匀浆液Ang II水平为(179.3±36.1) ng/g心肌组织，对照组心肌组织匀浆液Ang II水平为(103.2±13.6) ng/g心肌组织，心肌肥厚组心肌组织Ang II水平明显高于对照组（P<0.01）。心肌肥厚组CVF为39.5%±9.8%，对照组为20.9%±8.2%，心肌肥厚组明显高于对照组（P<0.01）；心肌肥厚组PVCA为1.98±1.05，对照组为0.41±0.12，心肌肥厚组也明显高于对照组（P<0.01）。心肌肥厚患者心肌组织I型胶原及III型胶原mRNA表达相对含量均明显高于正常人（均P<0.01）。心脏糜酶活性与CVF及PVCA呈明显正相关（相关系数分别为0.52和0.69，P<0.05和P<0.01）。心肌局部Ang II水平也与CVF及PVCA呈明显正相关（相关系数分别为0.49和0.58，均P<0.05）。结论: 心脏糜酶可增加胶原的合成，参与细胞外基质的形成和降解，促进心肌纤维化。     

缓激肽在依那普利对心肌梗死大鼠心肌肥厚及心功能影响中的作用

目的:探讨依那普利(enalapril)对大鼠心肌梗塞(M1)后心肌肥厚及心功能的影响是否与其抑制缓激肽(BK)降解的途径有关。方法:将大鼠随机分为:①假手术对照组(sham-operated control),②心肌梗死组(MI),③依那普利干预组(MI+enalapril),④依那普利和BKB₂受体阻断剂Hoe-140共同干预组(MI+enalapril+Hoe-140),⑤血管紧张素ⅡⅠ型受体阻断剂losartan干预组(Ml+losartan)。3个药物干预组从MI术后第3d开始给药,持续4周,然后测定左心室舒张末压(LVEDP)、+dp/dt_max及左心室重/体重(LVW/BW)、左心室非梗死区组织的平均(每核)心肌细胞体积,并进行组间比较。结果:3个药物干预组的LVEDP、LVW/BW及V(m)n均低于MI组(均Pp/dt_max和MI组相比无显著差别。3个药物干预组之间平均动脉压(MAP)无明显差异,但Ml+enalapril+Hoe-140组的LVW/BW及V(m)n的值却高于MI+enalapril组。结论:Enalapril可阻抑大鼠MI后的心肌肥厚并改善左心室功能,这种作用的部分机制是由于其促使了心肌组织BK的积累,即BK参与了enalapril阻抑心肌肥厚及改善心功能的作用,且这些作用不依赖于血压的影响。     

心肌梗塞后泵功能的恢复及其机制的实验研究

造成大鼠不同范围的心肌梗塞(MI)后,动态观察不同时期的静息和容量负荷状态下泵功能恢复的规律及其代偿机制。结果证明:(1)梗塞范围(IS)小于左室的46%时,泵功能都有自动恢复的可能性。IS越小,恢复越快、越好。IS超过46%时未见恢复;(2)在IS相同的条件上,静息状态的泵功能远较负荷状态的泵功能恢复得好;(3)MI后,泵功能代偿机制的代偿效应与IS呈反比。如IS超过46%,任何代偿机制均难以发挥效应。     

Hyperhomocysteinemia inhibited cardiac stem cell homing into the peri-infarcted area post myocardial infarction in rats

Background

Hyperhomocysteinemia (HHcy) has been reported as an independent risk factor for coronary artery disease; however it is not clear regarding the action of HHcy on the homing of cardiac stem cells (CSCs) to the damaged myocardium and the consequent CSCs-mediated cardiac repair post myocardial infarction.

Methods

Sprague–Dawley (SD) rats were divided into 4 groups. HHcy was induced in the rats by a 6-week high-methionine diet. Rat heart MI model was developed by left coronary artery ligation. Immunofluorescence was used to examine the CSCs migration in vivo via injecting BrdU-labeled CSCs into AV-groove followed by a coronary ligation. Immunohistochemistry, western blot and ELISA analysis were carried out to detect the expression of stem cell factor (SCF) protein, and RT-PCR was conducted for the expression of SCF mRNA.

Results

On day 5 of MI model creation, accumulation of CSCs was significantly increased in the peri-infarcted area by the non-hyperhomocysteinemic rats, which led to an improvement of cardiac function at 3 weeks after MI. however, the accumulation of CSCs was markedly decreased by the hyperhomocysteinemic rats followed with the decline of cardiac function. SCF expression was also significantly decreased in the peri-infarcted area by the hyperhomocysteinemic rats compared to the non-hyperhomocysteinemic rats. The experiments in vitro confirmed that homocysteine (Hcy) decreased SCF expression via inhibition of TNF-α-induced activity of NF-κB, further reduced the migration of CSCs.

Conclusion

It demonstrated that hyperhomocysteinemia may significantly contribute to restrain CSCs-mediated cardiac repair by reducing SCF-induced homing of CSCs.     

Blood gases at several levels of oxygenation in rats with a left-shifted blood oxygen dissociation curve

Theoretical deductions have shown that a shift of the blood O₂ dissociation curve (ODC) to the right might improve O₂ transport to tissues at normoxia and at mild hypoxia whereas at severe hypoxia the organism should be better off with an ODC shifted to the left (Turek et al., 1973b; Turek and Kreuzer, 1976). The present study was performed in order to ascertain this ambiguous effect of an ODC shift depending on the degree of hypoxia in intact animals. A major displacement of the ODC to the left was achieved in rats by chronic administration of sodium cyanate (NaOCN). Control animals received sodium chloride (NaCl) instead. Arterial and mixed-venous , , and pH were measured at normoxia and during breathing 14.9, 8.0, or 5.6% O₂ in N₂ in both groups. From , pH, ODC and arterial hematocrit, arterial and mixed-venous O₂ contents were estimated and as an index of blood O₂ extraction was obtained. At normoxia and during breathing 14.9% O₂ the NaOCN rats had a lower mixed-venous than the NaCl rats without any difference in pH. Arterio-venous O₂ difference did not differ at normoxia but was lower in NaOCN rats at 14.9% O₂. However, at 8.0 and 5.6% O₂ the NaOCN rats had a higher mixed-venous , an increased , and a higher pH (arterial and mixed-venous). At 5.6% O₂ the NaCl rats developed a severe acidosis concomitant with pronounced hypocapnia. These findings confirm that rats with a left-shifted ODC have an impaired O₂ transport to tissues at normoxia and mild hypoxia but a more efficient O₂ transport at severe hypoxia as compared with rats with an unshifted ODC, in agreement with our previous theoretical studies.Preliminary communications of part of this material at the FASEB Meeting in Anaheim, California, on April 11–16, 1976 (Fed. Proc.35, 526, 1976), and at the Dutch Federation Meeting in Amsterdam on April 21–23, 1976 (Volume of Abstracts, p. 381)     

Transplantation of platelet gel spiked with cardiosphere-derived cells boosts structural and functional benefits relative to gel transplantation alone in rats with myocardial infarction

The emerging field of stem cell therapy and biomaterials has begun to provide promising strategies for the treatment of ischemic cardiomyopathy. Platelet gel and cardiosphere-derived cells (CDCs) are known to be beneficial when transplanted separately post-myocardial infarction (MI). We hypothesize that pre-seeding platelet gel with CDCs can enhance therapeutic efficacy. Platelet gel and CDCs were derived from venous blood and heart biopsies of syngeneic rats, respectively. In vitro, the viability, growth, and morphology of CDCs cultured in platelet gel were characterized. When delivered into infarcted rat hearts, platelet gel pre-seeded with CDCs was more efficiently populated with endogenous cardiomyocytes and endothelial cells than platelet gel alone. Recruitment of endogenous c-kit positive cells was enhanced in the hearts treated with gel with CDC. At 3 weeks, the hearts treated with CDC-seeded platelet gel exhibited the greatest attenuation of adverse left ventricular (LV) remodeling and the highest cardiac function (i.e., LV ejection fraction) as compared to hearts transplanted with Gel only or vehicle controls. Histological analysis revealed that, though some transplanted CDCs differentiated into cardiomyocytes and endothelial cells in the recipients’ hearts, most of the incremental benefit arose from CDC-mediated endogenous repair. Pre-seeding platelet gel with CDCs enhanced the functional benefit of biomaterial therapy for treating myocardial infarction.     

rAAV-mediated angiogenin gene transfer induces angiogenesis and modifies left ventricular remodeling in rats with myocardial infarction

In vitro studies have demonstrated that bovine angiogenin (ANG) significantly stimulates both the migration of endothelial cells and the formation of tubelike structures. The aim of this study was to explore whether ANG gene transfer could enhance vascularization, modify left ventricular remodeling, and attenuate cardiac dysfunction in rats with myocardial infarction (MI). We constructed a recombinant adeno-associated virus vector encoding the ANG gene (rAAV-ANG) and evaluated its angiogenic potential after regional transfection by intramyocardial injection immediately after left anterior descending artery ligation in rats. Four weeks after coronary artery ligation, rAAV-ANG transfection upregulated the myocardium ANG protein expression level in both normal and MI rats, and immunohistochemistry showed that the overexpressed ANG was distributed in the cytoplasm of cardiomyocytes. In rats with MI, rAAV-ANG treatment altered left ventricular remodeling, as indicated by a decrease in left ventricular end diastolic diameter, left ventricular end systolic diameter, cardiomyocyte diameter, ventricular weight to body weight ratio and interstitial fibrosis infiltration. We also found an increase in capillary density and partly restored cardiac function in the group receiving rAAV-ANG treatment. These results confirmed that in rats with MI, ANG gene transfer could induce angiogenesis, alter left ventricular remodeling, and attenuate cardiac dysfunction. This study provides a new choice of treatment for ischemic heart disease.     

Influence of a diet rich in fish oil on blood pressure,body weight and cardiac hypertrophy in spontaneously hypertensive rats

Summary The effects of a diet rich in fish oil on arterial blood pressure, body weight, left ventricular weight and heart rate have been investigated in 8 month old spontaneously hypertensive male rats (SHR) as compared to age-matched hypertensive controls. A diet containing 10% fish oil decreased blood pressure by about 40 mmHg within 20 days of starting the experiment, and this effect persisted over the observation period of 80 days. Permitting the animals free access to food, the body weight of the diet group increased by 25%. The degree of hypertrophy as evaluated by relating left ventricular weight to tibial length was significantly reduced (10%) in the diet fed group. Heart rate was increased by 53%. The study demonstrates that a diet rich in fish oil can lower arterial blood pressure over several weeks without a recognizable loss in function despite a considerable increase in body weight. It can be assumed that a more marked regression of left ventricular hypertrophy is counteracted by a reflex increase in sympathetic efferentation to the heart.     

Solubility of inert gases in dog blood and skeletal muscle

Solubility of H₂, Ar, CH₄ and SF₆ was determined at 310 K (37°C) in water, in saline (0.154 mol NaCl/l H₂O), in plasma and whole blood of dogs, and in homogenates of the dog gastrocnemius muscle. The liquids were equilibrated with pure gases, and the dissolved gases were extracted and measured by gas chromatography as described previously (Meyer, M.: Pflügers Arch. 375, 161–165, 1978). In saline, the solubilities were 4% (SF₆) to 15% (Ar) lower than in water. For dog blood the following mean values for the solubility coefficient (in mol · l^–1 · kPa^–1) were found: for H₂, 6.44; for Ar, 9.94; for CH₄, 11.44; for SF₆, 2.62. The red cell/plasma and the muscle/blood solubility ratios were near unity for H₂, Ar and CH₄ (ranging from 0.9 to 1.3); for SF₆, however, they were much higher (about 2.1), apparently due to the high solubility of SF₆ in hydrophobic substances (lipids).Supported by the Deutsche Forschungsgemeinschaft (SFB 89, Kardiologie Göttingen)     

瑞舒伐他汀联合厄贝沙坦对大鼠心肌肥厚性重构的影响

 目的: 探讨瑞舒伐他汀联合厄贝沙坦对心肌肥厚大鼠心室重构的影响。方法: SPF级体重240~300 g雄性SD大鼠50只随机分为对照组、模型组、瑞舒伐他汀组、厄贝沙坦组和联合组。除对照组外,其余4组大鼠连续14 d给予皮下注射异丙肾上腺素(2.5 mg/kg)。自造模当天开始,对照组和模型组给予生理盐水灌胃,瑞舒伐他汀组、厄贝沙坦组和联合组分别给予瑞舒伐他汀(4 mg·kg^-1·d^-1)、厄贝沙坦(15 mg·kg^-1·d^-1)和瑞舒伐他汀(4 mg·kg^-1·d^-1)+厄贝沙坦(15 mg·kg^-1·d^-1)灌胃处理,连续干预4周。干预结束后,分别测定各组大鼠心脏质量指数、左室质量指数,HE染色观察心肌细胞肥大程度,RT-PCR测定肥大相关因子ANF、β-MHC和AT1受体(AT1R)的mRNA表达,Western blot法测定AT1R的蛋白表达。结果: 与对照组相比,模型组的心脏质量指数、左室质量指数、ANF和β-MHC的mRNA表达均增加(P<0.05);与模型组相比,瑞舒伐他汀组和厄贝沙坦组的心脏质量指数、左室质量指数、ANF和β-MHC的mRNA表达均降低(P<0.05),联合组效果优于单药组(P<0.05)。瑞舒伐他汀组及厄贝沙坦组AT1R的mRNA及蛋白表达均低于模型组(P<0.05),而联合组AT1R的mRNA及蛋白表达水平低于各单独用药组(P<0.05)。结论: 瑞舒伐他汀及厄贝沙坦均能不同程度地改善心肌肥厚。它们的抗心肌肥厚作用可通过下调AT1R的mRNA和蛋白表达实现。联合用药的效果优于单一药物。     

急性心肌梗死后心脏TGF-β1的表达和心室重塑(英文)

目的：探讨大鼠急性心肌梗死（AMI）后心肌纤维化和TGF-β1表达及炎症反应的分子机制。 方法： 建立大鼠AMI模型及假手术组，于术后第1、4和8周末测血流动力学后取心脏。RT-PCR和免疫组化SABC法检测TGF-β1基因和蛋白的表达。用氯胺T法测心肌组织羟脯氨酸的含量。心肌病检观察心肌组织炎症细胞浸润情况。 结果： 与假手术组相比，AMI后第1、4和8周末血流动力学有明显改变(P<0.01)。在梗死区、交界区和非梗死区羟脯氨酸和TGF-β1基因和蛋白表达均增高（P<0.05），第1周的表达高于第4和8周。羟脯氨酸和TGF-β1蛋白表达呈现明显正相关（r＝0.75－0.99，P<0.05）。AMI后第1周梗死区和交界区炎症细胞浸润明显，第4和8周心肌炎症细胞减少。TGF-β1在梗死后1周时主要见于心肌细胞、中性粒细胞、巨噬细胞和部分淋巴细胞的胞浆内表达，在4周和8周见于成纤维母细胞及间质。 结论： AMI后心肌细胞、炎症细胞、成纤维母细胞胞浆及基质中TGF-β1表达增高，与羟脯氨酸的变化及炎症过程存在联系，可能在AMI后心室重塑和心肌炎性修复过程中起重要作用。     

Livin基因修饰的骨髓间充质干细胞移植治疗对急性心肌梗死大鼠心功能的影响

 目的: 探讨livin修饰的骨髓间充质干细胞(MSCs)移植改善急性心肌梗死大鼠心功能的作用及livin和促凋亡蛋白caspase-3、caspase-7、caspase-9在感染后的表达情况。方法: 通过全骨髓培养法分离培养骨髓间充质干细胞,感染携带livin基因的重组腺病毒后用流式检测其对MSCs凋亡的影响。通过Western blot法分别检测livin、caspase-3、caspase-7和caspase-9的蛋白表达情况。采用冠状动脉左前降支结扎法建立心肌梗死模型,然后实验分4组进行:无胎牛血清的DMEM组;单纯干细胞治疗组(MSCs组);空载腺病毒转染干细胞组(rAd-control/MSCs)组;livin基因转染干细胞组(rAd-livin/MSCs组)。1个月后采用生理仪记录各组大鼠左室收缩压(LVSP)、左室舒张末压(LVEDP)、左室内压最大上升速率(+dp/dt_max)和左室内压最大下降速率(-dp/dt_max)来评价大鼠心功能。结果: rAd-livin/MSCs组凋亡率较MSCs组和rAd-control/MSCs组显著降低(P<0.05);rAd-livin/MSCs组抗凋亡蛋白livin明显上升(P<0.05),促凋亡蛋白caspase-3、caspase-7及caspase-9表达显著下降(P<0.05);细胞移植后1个月,rAd-livin/MSCs组心功能比MSCs组改善更明显(P<0.05)。结论: rAd-livin感染MSCs后可促进抗凋亡蛋白livin的表达,同时降低促凋亡蛋白caspase-3、caspase-7和caspase-9的表达及细胞凋亡率。rAd-livin/MSCs移植能进一步改善心肌梗死大鼠心功能。     

伊贝沙坦和培垛普利对大鼠压力负荷性心肌肥厚的影响

目的:探讨钙调神经磷酸酶和钙泵活性在大鼠压力负荷性心肌肥厚时的变化及伊贝沙坦和培垛普利对它们的影响。方法:40只雄性SD大鼠随机分为5组。除假手术组外,其余4组大鼠采用腹主动脉部分结扎法造成压力负荷性心肌肥厚模型,术后1周分别用下列药物开始灌胃:假手术组和对照组生理盐水2mL·kg^-1·d^-1,伊贝沙坦组20mg·kg^-1·d^-1,培垛普利组2mg·kg^-1·d^-1及联合用药组(培垛普利2mg·kg^-1·d^-1,伊贝沙坦20mg·kg^-1·d^-1)。用药6周后检测左室质量指数、心肌细胞横径、心肌钙调神经磷酸酶及钙泵活性,免疫组化测定心肌钙调神经磷酸酶的表达。结果:联合用药组LVMI显著低于对照组及单用伊贝沙坦或培垛普利药组,各用药组TDM及钙调神经磷酸酶活性显著低于对照组,对照组心肌肌浆网钙泵活性显著低于其他各组,联合用药组钙泵活性明显高于单独用药组。免疫组化显示对照组心肌组织钙调神经磷酸酶表达显著高于其他各组。相关分析显示LVMI与TDM、CaN均呈显著正相关,与钙泵活性呈负相关。结论:伊贝沙坦和培垛普利可抑制钙调神经磷酸酶活性,增加心肌肌浆网钙泵活性,联合应用对减轻心肌肥厚有协同作用。     

The T-type calcium channel blocker mibefradil reduced interstitial and perivascular fibrosis and improved hemodynamic parameters in myocardial infarction-induced cardiac failure in rats

Fibrillar collagen accumulates within the interstitium and around coronary arteries following cardiac failure and is responsible for abnormal myocardial stiffness and reduced coronary performance associated with impaired cardiac function. The aim of the study was to determine the effects of long-term treatment with the T-type calcium channel antagonist mibefradil on myocardial remodeling and cardiac function after chronic myocardial infarction (MI). MI was induced by permanent ligation of the left coronary artery in male Wistar rats. Animals were assigned to sham-operated, placebo-treated or mibefradil-treated (10 mg/kg per day p.o.) MI groups. Treatment with mibefradil was started either 7 days before, 24 h after, or 7 days after ligation and continued for 6 weeks after MI. At this time point, mean arterial blood pressure (MAP), heart rate (HR), left ventricular end-diastolic pressure (LVEDP) and cardiac contractility (dP/dt_max) were measured in conscious rats. Morphometric parameters were determined in picrosirius red-stained hearts: total heart weight (THW), interstitial and perivascular collagen volume fraction (ICVF, PCVF), myocardial infarct size (IS), vascular perimeter (VP), inner vascular diameter (IVD) and media thickness (MT). Six weeks after MI, MAP and dP/dt_max were decreased, and LVEDP was increased in placebo-treated animals. In mibefradil-treated animals whose treatment started 7 days before or 24 h after MI, MAP and dP/dt_max were higher, and LVEDP was lower than in placebo-treated controls. THW, ICVF, PCVF and MT were higher in placebo-treated animals. Mibefradil treatment resulted in higher ICVF and IS, higher VP and IVD (when started 7 days before MI) and lower PCVF and MT (when started 7 days before or 24 h after MI) than were observed in placebo-treated controls. Chronic treatment with mibefradil reduced interstitial and perivascular fibrosis and improved cardiac function in MI-induced heart failure in rats. Cardiac remodeling was best prevented when treatment was begun before the ischemic event. Received: 16 March 1999 / Accepted: 23 August 1999     

吡格列酮对心肌梗死大鼠心肌能量代谢及血流动力学的影响

目的: 探讨吡格列酮对心肌梗死后大鼠心肌能量代谢及血流动力学的影响。方法: 采用开胸结扎冠状动脉左前降支建立心肌梗死模型,取术后72 h存活的20只大鼠随机分为手术组(MI组,n=10)和吡格列酮干预组(P组,n=10,吡格列酮3 mg·kg^-1·d ^-1灌胃8周),另设假手术组(SH组,n=10)。分别喂养8周后用Western blotting法测定大鼠心肌组织中过氧化物酶体增殖物激活受体γ(PPARγ)的蛋白表达水平。用生物组织氧耗测量仪测定线粒体氧化呼吸活性,高效液相层析法(HPLC)法测量线粒体内腺苷酸含量;氚标记二磷酸腺苷(-ADP)掺入法检测线粒体膜腺苷酸转运体(ANT)转运活性,经颈动脉插管测定血流动力学参数,并计算心室重塑指标。结果: 与SH组比较,MI组PPARγ的蛋白表达水平明显下调(P<0.01),线粒体内高能磷酸盐含量、呼吸活性和ANT转运活性明显降低(P<0.01),血流动力学指标紊乱(P<0.01); 与MI组比较,吡格列酮8周干预升高PPARγ的蛋白表达水平,改善心梗后心衰大鼠线粒体呼吸活性及ANT转运活性,增加线粒体内高能磷酸盐含量(P<0.01),但血流动力学指标改善不显著。结论: 心肌梗死后心力衰竭过程中,吡格列酮干预活化PPARγ,升高PPARγ蛋白的表达,可改善心力衰竭大鼠心肌能量代谢;但对血流动力学指标改善不显著。     

急性心肌梗死大鼠趋化因子表达与心功能的关系

目的：探讨急性心肌梗死（AMI）大鼠心肌局部趋化因子的表达与淋巴细胞浸润及心功能的关系。 方法： 结扎冠状动脉左前降支建立AMI大鼠模型，实验动物分为3组：心衰组（MI-HF）、未心衰组(MI-NF)和假手术组(sham)，假手术组只过线不结扎。于术后3 d、1周、2周检测血流动力学，将左室舒张末期压力(LVEDP)≥15 mmHg者归为心衰组。用半定量RT-PCR方法测定心肌梗死区（包括梗死周边区）趋化因子的mRNA表达，包括γ干扰素诱导的单核因子（MIG）、巨噬细胞炎性蛋白-1α（MIP-1α）、正常T细胞表达和分泌、活化时表达下降的因子（RANTES）。HE染色切片进行梗死区淋巴细胞计数分析。 结果： AMI大鼠心肌局部趋化因子的mRNA表达于术后3 d开始升高，1周达峰值，且MI-HF组较MI-NF组表达更高(RANTES, 0.83±0.05 vs 0.51±0.19, P<0.05; MIP-1α, 1.94±0.30 vs 1.48±0.33, P<0.05; MIG, 1.40±0.27 vs 0.93±0.28, P<0.05)。RANTES和MIP-1α的表达与淋巴细胞浸润显著相关(RANTES，r=0.35，P<0.05；MIP-1α，r＝0.40，P<0.05)。 结论： AMI后心肌局部趋化因子RANTES、MIP-1α、MIG表达增高，且趋化因子水平与心功能有相关性，趋化因子可能参与了AMI后心衰的病理生理学发展过程。     

丹参提取物促大鼠心肌梗死后心肌组织血管新生的作用

目的:观察丹参提取物对大鼠心肌梗死后心肌组织血管新生的作用并分析其可能的机制。方法:采用经典的冠状动脉左前降支结扎造模方法成功复制大鼠心肌梗死模型后,随机将大鼠分为模型组以及丹参提取物低(10 mg·kg-1·d-1)、中(20 mg·kg-1·d-1)、高(40 mg·kg-1·d-1)剂量治疗组,另设假手术组大鼠为对照组,各组大鼠数量均为8只。丹参提取物各治疗组给予上述对应的各药物剂量灌胃给药,模型组及对照组大鼠给予等量的生理盐水灌胃,连续饲养4周后应用HE染色、Masson染色和电镜法观察大鼠左心室心肌组织和血管结构病理成分变化,免疫组化染色分析心肌组织中血管内皮生长因子(VEGF)及CD34蛋白的表达变化。结果:组织病理学分析表明,与假手术组相比,模型组大鼠心肌组织形态较为紊乱,部分心肌细胞轮廓消失,坏死心肌组织呈现明显的纤维化,血管不完整,血管超微结构模糊或者消失;丹参提取物治疗之后,新生的血管数量明显增多,且超微结构分析表明,内皮细胞形态相对完整。心肌组织中VEGF及CD34蛋白表达结果证实,模型组较假手术组大鼠表达略有增加,但没有统计学差异;和模型组比较,丹参提取物各治疗组VEGF及CD34蛋白表达明显增多(P0.01)。结论:丹参提取物可明显促进大鼠心肌梗死后心肌组织的血管新生。