参芍口服液对急性心肌梗死大鼠的心肌保护作用分析

目的 探究参芍口服液对急性心肌梗死(AMI)大鼠的心肌保护作用及机制。方法 将60只SD大鼠随机分为假手术组、模型组及低、中、高剂量(3.2、6.4、12.8 ml/d)参芍口服液组和阳性对照组[贝那普利10 mg/(kg·d)],除假手术组外,其余大鼠均手术结扎冠状动脉制备AMI模型,假手术组仅开胸未结扎,药物干预4周后,行超声心动图评估各组大鼠左心室功能和结构,HE染色观察各组大鼠心肌组织病理学变化,比较各组大鼠血清肌酸激酶(CK)、心肌型肌酸激酶同工酶(CK-MB)、脑钠肽(BNP)水平,ELISA检测外周血白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)水平,行免疫组织化学染色和Western blot实验检测各组大鼠心肌组织Wnt10b、β-catenin蛋白表达。结果 与模型组比较,中、高剂量参芍口服液组和阳性对照组大鼠心肌组织病理损伤有不同程度改善,左心室射血分数、左心室短轴缩短率升高,左心室舒张末期内径、左心室收缩末期内径、左心室舒张末期容积和左心室收缩末期容积及血清CK、CK-MB、BNP、IL-1β、IL-6、TNF-α水平...     

脑出血大鼠血清IL-17,IL-23的表达及意义

目的:以脑出血大鼠为研究对象,探讨血清IL-17,IL-23的表达及意义.方法:将90只大鼠随机分成3组:对照组(A组),假手术组(B组),出血组(C组),每组30只.分别设6h,24h,3d,7d,14d五个时间点.用酶联免疫吸附法(ELISA)检测大鼠血清中白细胞介素17(IL-17)、白细胞介素23(IL-23)的表达.结果:对照组与假手术组IL-17,IL-23的表达在各时间点均无统计学差异(P＞0.05).出血组与对照组、假手术组相比、同一时间点IL-17,IL-23的表达均具有统计学差异(P＜0.05).出血组内各时间点IL-17,IL-23的表达相比,均具有统计学差异(P＜0.05).IL-17,IL-23的表达在脑出血后7d高于出血其他时间点,具有统计学差异(P＜0.05).结论:脑出血大鼠发病6h后,外周血中IL-17,IL-23的表达增加;IL-17,IL-23的表达在脑出血后7d高于6h,24h,3d,14d.IL-17,IL-23参与脑出血后的炎症反应.     

灯盏花素对心肌缺血再灌注损伤大鼠的心肌保护作用

目的 观察灯盏花素对心肌缺血再灌注损伤（myocardial ischemia-reperfusion injury,MIRI）大鼠的心肌保护作用,并探讨其可能的机制。方法 将60只SD大鼠随机分为健康组、模型组、灯盏花素低剂量和灯盏花素高剂量组,各15只;灯盏花素低剂量、灯盏花素高剂量组大鼠腹腔注射灯盏花素（50、100 mg·kg-1）;健康组、模型组大鼠腹腔注射等体积生理盐水。每日1次,干预5d。模型组、灯盏花素低剂量组、灯盏花素高剂量组最终均纳入10只大鼠。检测心电图指标;2,3,5-氯化三苯基四氮（2,3,5-triphenyltetrazolium chlorid,TTC）染色检测心肌梗死面积;检测血清心肌损伤指标;检测血清氧化应激指标;检测血清炎性因子水平;蛋白质印迹法（Western blotting）检测心肌组织白细胞介素-23(interleukin-23,IL-23)、白细胞介素-17(interleukin-17,IL-17)蛋白的表达水平。结果 与模型组比较,灯盏花素低剂量组大鼠室颤（ventricular fibrillation,VF）和室性心动过速（ve...     

阿托伐他汀对急性心肌梗死后慢性心力衰竭大鼠心肌 IL-6 表达的影响简

目的 探讨阿托伐他汀对急性心肌梗死后慢性心力衰竭的抑制作用及机制.方法 45只雄性急性心肌梗死模型大鼠随机均分为阿托伐他汀高、低剂量组及模型组(n＝15).另取10只大鼠作为假手术组.阿托伐他汀高、低剂量组分别给予阿托伐他汀20,10 mg.kg^-1.d^-1,灌胃6周,假手术组和模型组不予治疗.第6周末以超声心动图检测各组大鼠左心室形态功能变化,测定左室心肌肥厚指数(LVHI).假手术组取位于左心室游离壁心肌组织,心肌梗死各组取位于左心室梗死区、交界区心肌组织分别以免疫荧光激光共聚焦显微镜及Western blot检测白细胞介素(IL)-6表达. 结果模型组、阿托伐他汀高、低剂量组大鼠左室舒张期内径(LVEDD)、左室收缩内径(LVESD)、舒张末期容积(EDV)、收缩末期容积(ESV)、LVHI、心肌IL-6水平较假手术组均显著升高(P<0.05或P<0.01);左室射血分数(LVEF)较假手术组降低(P<0.05或P<0.01).与模型组比较,高、低剂量阿托伐他汀组大鼠LVEDD、LVESD、EDV、ESV、LVHI、心肌IL-6水平均显著降低(P<0.05或P<0.01),LVEF显著升高(P<0.05或P<0.01).与阿托伐他汀低剂量组比较,高剂量组大鼠LVEDD、LVESD、EDV、ESV、LVHI、心肌IL-6水平均显著降低(P<0.05),LVEF显著升高(P<0.05).结论 阿托伐他汀可能通过抑制IL-6过度表达而发挥抑制心室重塑作用,其作用呈剂量依赖性.     

IL-17对大鼠心肌梗死后心律失常和心室重塑的影响分析

目的 探讨白细胞介素-17(IL-17)对大鼠心肌梗死后心律失常和心室重塑的影响.方法 液氮冷冻法获取心肌梗死大鼠共72只,按照随机原则分为心梗对照组、IgG1处理组和IL-17抗体处理组,剩余24只大鼠作为空白对照组,四组大鼠组内按照随机原则分别实验处理1个月和2个月,检测四组大鼠心肌IL-17表达水平,记录心律失常和心室重塑相关指标.结果 实验处理后心梗对照组和IgG1处理组大鼠各项指标均未表现出明显差异(P>0.05),心肌梗死各组大鼠心肌IL-17表达水平、心律失常诱发率、Ⅰ/Ⅲ胶原比例均明显高于空白对照组(P<0.05),超声心动图显示心脏功能明显次于空白对照组(P<0.05),IL-17抗体处理组上述指标较心梗对照组和IgG1处理组明显改善(P<0.05),心肌IL-17表达水平与心律失常诱发率呈明显的正相关关系(r=0.89,P<0.05).结论 心肌梗死大鼠心肌IL-17大量表达,对心律失常和心室重塑的形成具有很大的诱导作用.     

二苯乙烯苷对糖尿病大鼠心肌损伤的保护作用

目的探讨二苯乙烯苷(TSG)对糖尿病大鼠心肌损伤的作用及对沉默信息调节因子2的哺乳动物同源体1(SIRT1)和磷酸腺苷活化的蛋白激酶(AMPK)蛋白影响。方法建立2型糖尿病大鼠模型,分组给药,16周时处死大鼠,生化法测定血糖、血脂、肝功能及肌酸激酶(CK)、乳酸脱氢酶(LDH)和心肌组织游离脂肪酸(NEFA);酶联免疫吸附法测定心肌肌钙蛋白Ⅰ(cTnⅠ)、心肌组织脂代谢相关酶脂肪酸跨膜转运载体蛋白(FATPs)和脂肪酸β氧化酶(FA-β-oxidase)的含量;放射免疫法测定血浆炎症因子肿瘤坏死因子(TNF-α)、白细胞介素6(IL-6)、白细胞介素1β(IL-1β)的含量,Western blot检测心肌组织中TNF-α、IL-6、IL-1β、SIRT1和AMPK蛋白的表达;并测定左心室胶原含量。结果TSG干预后能减低血脂水平,对血糖和胰岛素水平无明显影响。TSG能减低糖尿病大鼠心肌组织中胶原含量,减少心脏游离脂肪酸含量,增加心肌组织脂代谢相关酶(FATPs和FA-β-oxidase)含量,抑制外周血和心肌组织中炎症因子(TNF-α、IL-6、IL-1β)的分泌。TSG能明显增加糖尿病大鼠心脏SIRT1和p AMPK蛋白表达。结论 TSG对糖尿病大鼠心肌具有保护作用,其机制可能与抑制心肌炎症因子和改善能量代谢有关。     

雷公藤甲素通过上调miR-137调控小胶质细胞极化改善大鼠抑郁样行为

目的 探讨雷公藤甲素通过上调miR-137调控小胶质细胞极化改善抑郁症的作用及潜在分子机制。方法 50只SD大鼠随机分为对照组、模型组、雷公藤甲素组、雷公藤甲素+NC抑制剂组和雷公藤甲素+miR-137抑制剂组,每组10只。通过构建慢性不可预知性应激（CUS）抑郁大鼠模型,采用糖水偏好实验、强迫游泳实验和悬尾实验检测大鼠的行为学变化,实时定量聚合酶链反应（RT-qPCR）检测大鼠海马中miR-137的表达水平,Western blotting分别检测大鼠海马组织中离子钙接头蛋白分子-1(Iba-1)、诱导型一氧化氮合酶（iNOS）和精氨酸酶1(Arg1)蛋白表达,ELISA法检测大鼠海马中神经递质5-羟色胺（5-HT）和多巴胺（DA）水平以及炎性因子白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、白细胞介素-4(IL-4)、白细胞介素-10(IL-10)的水平。结果 与对照组比较,模型组大鼠糖水偏好百分比显著降低,不动时间显著增加,体质量明显下降,海马中miR-137表达显著降低,Iba-1和iNOS蛋白以及IL-1β和IL-6水平显著增加,Arg1蛋白、5-HT、DA、I...     

麻芩消咳颗粒平喘消炎作用研究

目的探讨麻芩消咳颗粒的平喘抗炎作用。方法SD大鼠随机分为6组,分别为肺宁颗粒2.5 g·kg^-1组、麻芩消咳颗粒(1、2、4 g·kg^-1)组、模型组和溶剂对照组。第0、7天皮下注射卵蛋白混悬液致敏。第15天开始给药并用1%的OVA溶液激发哮喘,每天给药1次,连续给药4周。给药结束后检测大鼠肺泡盥洗液中白细胞介素6(IL-6)、白细胞介素17(IL-17)含量及血清中免疫球蛋白E(IgE)、白细胞介素4(IL-4)水平,观察肺组织病理学变化,Western blot检测肺组织中PI3K、p-PI3K、AKT、p-AKT的表达水平。结果麻芩消咳颗粒2 g·kg^-1能够降低大鼠肺泡盥洗液中白细胞介素6、白细胞介素17含量及血清中免疫球蛋白E、白细胞介素4水平,降低PI3K、ATK磷酸化水平。结论麻芩消咳颗粒对卵蛋白诱发的大鼠过敏性哮喘模型有显著的平喘抗炎作用,与PI3K/AKT调节的炎症信号通路有关。     

豨莶草对大鼠佐剂型关节炎的治疗作用及机制研究

摘要：目的:通过佐剂型大鼠关节炎模型探讨豨莶草对类风湿关节炎的治疗作用及机制研究。方法:豨莶草药材粉碎后乙醇加热回流制成干浸膏。60只雄性大鼠随机分为6组:正常对照组、模型组、美洛昔康组(40.0 mg·kg-1)、豨莶草高、中、低剂量组(1.6,0.8,0.4 g·kg-1),每组10只。通过注射完全弗氏佐剂进行刺激,构建佐剂型关节炎模型,造模成功后美洛昔康和豨莶草组灌胃给药,模型组和正常对照组给予等体积生理盐水,1次/d,持续28 d。测量大鼠足跖肿胀度、脾脏脏器系数,HE染色观察关节滑膜组织病理变化,Western blot检测关节滑膜NLRP3炎性小体的表达,ELISA检测血浆白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、C反应蛋白（CRP）、干扰素-γ（IFN-γ）、白细胞介素18（IL-18）的表达。结果:与正常对照组比较,模型组大鼠足跖肿胀度和脾脏系数明显增大,关节滑膜内NLRP3蛋白表达及血浆IL-1β、IL-6、TNF-α、CRP、IFN-γ、IL-18明显升高（P<0.05）。与模型组比较,豨莶草各剂量组大鼠足跖肿胀度和脾脏系数明显减少,关节滑膜内NLRP3蛋白表达及血浆IL-1β、IL-6、TNF-α、CRP、IFN-γ、IL-18明显降低（P<0.05）。结论:豨莶草高、中剂量组均可能通过抑制NLRP3炎性小体的表达,从而抑制滑膜细胞增殖,调节炎性因子生成,进而抑制类风湿关节炎的炎性反应,以达到减轻关节损伤的作用。     

罗格列酮对慢性阻塞性肺疾病炎症损伤的保护机制研究

目的探讨罗格列酮对慢性阻塞性肺疾病(COPD)大鼠的作用及潜在作用机制。方法 30只雄性SD大鼠随机均分为对照组、COPD模型组和罗格列酮组。通过烟雾暴露联合气道滴入脂多糖构建大鼠COPD模型。罗格列酮组在烟雾暴露前30 min给予罗格列酮(20μg/只)灌胃,对照组和模型组给予等量生理盐水灌胃,共30 d。处死大鼠前观察大鼠一般情况,并行肺功能测定和收集支气管肺泡灌洗液(BALF)行细胞分类计数,处死后收集肺脏和血清。HE染色观察肺组织病理形态; ELISA和RT-PCR检测血清、BALF和肺组织中白细胞介素(IL)-6、IL-1β和肿瘤坏死因子(TNF-α)表达水平; Western blot检测肺组织PI3K、p-AKT和AKT蛋白表达水平。结果与模型组比较,罗格列酮预处理可明显减轻肺组织病理损伤,改善大鼠肺功能和一般情况,降低IL-6、IL-1β、TNF-α的表达水平,降低BALF中的中性粒细胞总数和中性粒细胞比,提高PI3K和p-AKT表达水平,而对AKT表达无影响。结论罗格列酮可通过抑制炎症减轻COPD大鼠肺功能的恶化,其作用机制与促进PI3K/AKT信号通路激活相关。     

Regulation of inflammation and myocardial fibrosis in experimental autoimmune myocarditis

Autoimmune responses and inflammation are involved in the pathogenesis of many cardiovascular diseases. There is compelling evidence that inflammatory mechanisms may contribute to progressive heart failure. Thus, myocardial infiltration of lymphocytes and mononuclear cells, increased expression of pro-inflammatory chemokines and cytokines and circulating autoantibodies are frequently observed in myocarditis and dilated cardiomyopathy (DCM). Experimental autoimmune myocarditis (EAM) in rodents may be elicited by immunization of cardiac myosin and EAM in rats mimics human fulminant myocarditis in the acute phase and human DCM in the chronic phase. Our animal model, EAM was demonstrated to progress into the clinicopathological state similar to DCM in the chronic phase, and was found to be characterized by the enlargement of the heart, dilatation of ventricles, diffuse and extensive myocardial fibrosis, besides being a cellular immunity and inflammation mediated disease. Severity of myocarditis was characterized by increased inflammation, cardiac fibrosis and decreased myocardial performance in rats with DCM. Pharmacological interventions such as angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARBs) significantly attenuated the myosin-induced inflammation and cardiac fibrosis and thereby improving myocardial function in rats with DCM. A growing body of evidence shows that ACEI and ARBs contribute to the pharmaceutical management of patients with heart failure mediated by immune and inflammatory response. The purpose of this review is to emphasize the role of inflammation and myocardial fibrosis in rats with DCM after EAM and study the effects of pharmacological interventions such as ACEI, ARBs in the treatment of heart failure through the suppression of inflammatory cytokines and fibrosis.     

Effects of humoral factors on left ventricular remodeling under chronic heart failure

Chronic heart failure is a slowly progressive disease. Hemodynamic deterioration activates various neuro-humoral factors and increases stresses, such as catecholamine, angiotensin II (AII), cytokines, endothelin, wall stress, ischemia, tachycardia, and oxidative stress. These factors affect the myocardium to cause phenotype switching, leading to ventricular remodeling. We investigated the effects of pharmacological blocking for neuro-humoral factors in rats with dilated cardiomyopathy. Experimental autoimmune myocarditis (EAM) was elicited in Lewis rats by immunization with cardiac myosin. After acute inflammation healed, rats were treated with angiotensin converting enzyme inhibitors (ACEI), type 1 AII receptor blockers, and amiodarone. These agents had favorable effects on hemodynamics and myocardial contractility, prevented fibrosis, suppressed the expression of ANP, and reversed phenotypic change of cardiac myosin. AII receptor blockers were less effective than ACEI. In order to prevent ventricular remodeling in chronic heart failure, wide and complete blocking of neuro-humoral factors is important.     

童心康合剂对实验性自身免疫性心肌炎大鼠心肌纤维化的影响

目的:探讨童心康合剂对实验性自身免疫性心肌炎(EAM)模型大鼠心肌纤维化的影响。方法:将60只Lewis大鼠随机分为正常对照组、EAM模型组、玉丹荣心丸组、童心康合剂高、中、低剂量组,每组10只。于免疫56d处死存活大鼠,观察心肌病理变化、Masson染色观察心肌纤维化,免疫组化测心肌组织金属蛋白酶-9(MMP-9)及其组织抑制物-1(TIMP-1)的表达。结果:童心康合剂大中剂量组与玉丹荣心丸组心肌病理积分均低于EAM模型组(P<0.05),3组之间差异无显著性(P>0.05),童心康合剂小剂量组与EAM模型组病理积分差异无显著性(P>0.05)。童心康合剂大中剂量、玉丹荣心丸均能抑制心肌纤维化,童心康合剂大中剂量均优于玉丹荣心丸(P<0.05),且2组之间差异无显著性(P>0.05)。童心康合剂中剂量能上调心肌组织MMP-9的表达,下调其TIMP-1的表达。结论:童心康合剂大中剂量、玉丹荣心丸可减轻EAM模型大鼠心肌炎症,抑制心肌纤维化,此作用可能与调节MMP-9/TIMP-1平衡有关。     

Chinese medicinal herb Radix Astragali suppresses cardiac contractile dysfunction and inflammation in a rat model of autoimmune myocarditis

Radix Astragali, a Chinese medicinal herb, consists of polysaccharides and flavonoids as its main active ingredients. It has been widely used for treatment of cardiovascular diseases such as heart failure, angina pectoris, myocardial infarction and stroke in Asian countries. This study was designed to evaluate the effect of Radix Astragali on myocardial dysfunction, cardiac remodeling and morphological alteration in an experimental model of autoimmune myocarditis, a clinical condition often resulting in dilated cardiomyopathy. Experimental autoimmune myocarditis was established with a subcutaneous injection of porcine cardiac myosin into rear footpad in Lewis rats. Radix Astragali treatment was delivered via an intravenous injection (0.2 ml/100g body weight, daily) for 3 weeks. Results from transthoracic echocardiography indicated that experimental autoimmune myocarditis led to impaired myocardial contractile function which was reconciled by Radix Astragali. The experimental autoimmune myocarditis triggered profound inflammation and fibrosis in myocardium as assessed by hematoxylin and eosin (H and E) and Masson's trichrome staining. Interestingly, Radix Astragali significantly attenuated autoimmune myocarditis-induced myocardial inflammation and fibrosis. Similarly, Radix Astragali treatment alleviated autoimmune myocarditis-triggered overt lymphocyte proliferation. Furthermore, Radix Astragali significantly attenuated elevated levels of the Th1 cytokines (IFN-gamma and IL-2), and increased the Th2 cytokines (IL-4 and IL-10) in autoimmune myocarditis. Collectively, our data revealed that Radix Astragali effectively protected against cardiac functional and morphological aberrations in experimental autoimmune myocarditis.     

The emerging role of galectins in cardiovascular disease

Galectins are an ancient family of β-galactoside-specific lectins and consist of 15 different types, each with a specific function. They play a role in the immune system, inflammation, wound healing and carcinogenesis. In particular the role of galectin in cancer is widely studied. Lately, the role of galectins in the development of cardiovascular disease has gained attention. Worldwide cardiovascular disease is still the leading cause of death. In ischemic heart disease, atherosclerosis limits adequate blood flow. Angiogenesis and arteriogenesis are highly important mechanisms relieving ischemia by restoring perfusion to the post-stenotic myocardial area. Galectins act ambiguous, both relieving ischemia and accelerating atherosclerosis. Atherosclerosis can ultimately lead to myocardial infarction or ischemic stroke, which are both associated with galectins. There is also a role for galectins in the development of myocarditis by their influence on inflammatory processes. Moreover, galectin acts as a biomarker for the severity of myocardial ischemia and heart failure.This review summarizes the association between galectins and the development of multiple cardiovascular diseases such as myocarditis, ischemic stroke, myocardial infarction, heart failure and atrial fibrillation. Furthermore it focuses on the association between galectin and more general mechanisms such as angiogenesis, arteriogenesis and atherosclerosis.     

Suppression of experimental autoimmune myocarditis by sodium fusidate (fusidin)

Fusidic acid and its sodium salt sodium fusidate (fusidin) are widely used antibiotics that possess immunomodulating properties. It has been shown that fusidin ameliorates the course of several organ-specific immunoinflammatory diseases and thus we investigated the effect of fusidin on myosin-induced experimental autoimmune myocarditis (EAM) in rats, a well-established animal model for human giant cell myocarditis and postmyocarditis dilated cardiomyopathy (DCM). Fusidin at doses of 80 mg kg(-1) was administrated i.m. to male Dark Agouti (DA) rats, either from days 0 to 10 (early treatment group), or from days 10 to 20 (late treatment group) after induction of EAM. Efficacy of fusidin treatment was determined on day 21 of EAM development. It was observed that both early and late treatment with fusidin markedly ameliorated clinical, histological and immunohistochemical signs of the disease. The treated rats had significantly decreased incidence of EAM, heart weight and heart weight/body weight ratio (Hw/Bw) compared with untreated animals. In contrast to the severe myocardial damage and cellular infiltration in the EAM rats, there was only focal infiltration of inflammatory cells in the myocardium of the treated rats. In both treated groups the mean microscopic score was markedly lower compared with vehicle-treated animals. In addition, the number of CD4+, ED1+ and OX6+ cells was significantly lower in myocardium of fusidin-treated rats than that in untreated group. The present findings suggest that fusidin exhibited both early and late therapeutical effect in EAM.     

卡托普利和低剂量阿司匹林相互作用对心衰大鼠左室心肌组织c-fos蛋白表达的影响

目的 观察卡托普利和低剂量阿司匹林相互作用对冠状动脉结扎致心衰大鼠模型左室心肌组织c—fos蛋白表达的影响。方法 采用冠状动脉结扎致急性心肌梗死和心梗后慢性心力衰竭大鼠模型，按照正交设计试验方案给药5wk，采用免疫组织化学方法观察联用两药对左室心肌组织c—fos蛋白表达的影响。结果 急性心肌梗死组c—fos蛋白阳性颗粒数目明显增多，卡托普利各剂量组对心肌组织c—fos蛋白表达均无影响，且与低剂量阿司匹林无显的相互作用，而低剂量阿司匹林增加c—fos蛋白免疫反应阳性细胞分布，尤以急性心肌梗死组多见。结论 低剂量阿司匹林介导c—fos蛋白表达增加，可能是其拮抗卡托普利减轻心衰大鼠左室重建作用的机制之一。     

缬沙坦降低慢性肾衰竭大鼠心肌内皮素的表达

目的：观察缬沙坦对慢性肾衰竭大鼠心肌肥厚及心肌内皮素-1（ET-1）表达的影响,探讨其作用机制。方法：SD雄性大鼠24只,通过5/6肾切除法制备慢性肾衰竭模型,术后2周随机分为模型组、缬沙坦组,并设假手术组作为对照。术后第10周末测定各组大鼠血压及肾功能（BUN、Cr）后处死大鼠,取出心脏进行病理组织形态学观察;并采用原位杂交方法检测心肌ET-1 mRNA转录水平。结果：模型组术后第10周收缩压、心脏重量、心脏重量指数、左室重量及左室重量指数均明显增加,缬沙坦组能显著降低5/6肾切除大鼠收缩压、心脏重量、心脏重量指数、左室重量及左室重量指数（P〈0.01）;缬沙坦组心肌ET-1 mRNA转录水平较模型组减弱。结论：缬沙坦能改善慢性肾衰竭大鼠的左室肥厚,其机制可能是通过下调心肌ET-1 mRNA转录来实现的。     

Beneficial effects of milrinone and enalapril on long-term survival of rats with healed myocardial infarction

The long-term survival of rats with healed myocardial infarction and congestive heart failure treated with milrinone, enalapril and the combination of milrinone plus enalapril, was documented. Seven days after sham or coronary ligation, 200 rats (99 sham and 101 myocardial infarcted) were randomized based on electrocardiographic criteria to receive tap water, milrinone (20-40 mg/l drinking water), enalapril (17-25 mg/l) or the combination of milrinone plus enalapril (20-40 mg/17-25 mg per l). The date of spontaneous death was recorded and heart weights and myocardial infarct size (by planimetry) were determined. Long-term enalapril therapy prolonged survival with a median 50% survival (MS50) of 233 days compared to 203 days in the tap water group. Milrinone therapy also prolonged survival with a MS50 of 297 days. The combination therapy prolonged survival with a MS50 of 277 days. In general, there were three times as many rats alive in the treatment groups at the end of one year compared to untreated control groups. Cardiac hypertrophy was evident in all myocardial infarcted groups and heart weights were significantly reduced by all treatments. The average myocardial infarct sizes and the distribution of infarct sizes were not different between groups (36.8-43% of left ventricle). This study demonstrates that long-term therapy with enalapril and milrinone prolongs survival in rats with healed myocardial infarctions. The prolongation of survival was comparable in the milrinone plus enalapril groups, indicating that there was no synergy with these two agents with survival as the end point.     

Torasemide, a long-acting loop diuretic, reduces the progression of myocarditis to dilated cardiomyopathy

Torasemide is a long-acting loop diuretic that combines the effects of both furosemide and spironolactone. It has been reported that torasemide may block the renin-angiotensin-aldosterone system and therefore it might attenuate myocardial remodeling accompanied by left ventricular dysfunction. However, nothing is known about the effect of torasemide on myocardial remodeling in a rat model in which myosin-induced experimental autoimmune myocarditis might develop into dilated cardiomyopathy. Experimental autoimmune myocarditis was elicited in Lewis rats by immunization with porcine cardiac myosin. Twenty-eight days after immunization, we investigated the effects of torasemide on metabolic and neurohumoral parameters, cardiac fibrosis and remodeling in experimental autoimmune myocarditis rats. Diuresis was increased dose-dependently by torasemide; the urinary potassium and sodium excretion was significantly decreased and increased, respectively. Myocardial functional parameters measured by hemodynamic and echocardiographic studies were significantly improved by torasemide treatment in a dose-dependent manner. The area of fibrosis, myocyte size and the myocardial protein levels of transforming growth factor-beta1, collagen III, and aldosterone synthase were significantly decreased, and the sarcoplasmic reticulum Ca2+ ATPase2 protein level was significantly increased by torasemide treatment. Moreover, the plasma levels of angiotensin II and aldosterone were increased and atrial natriuretic peptide was decreased in a dose-dependent manner. Our results indicate that torasemide treatment significantly improved left ventricular function and ameliorated the progression of cardiac remodeling beyond its renal effects in rats with chronic heart failure after experimental autoimmune myocarditis.