羟基红花黄素A对血管内皮细胞黏附分子的影响

目的考察羟基红花黄素A对氧化损伤血管内皮细胞表达黏附分子[血管内皮细胞黏附分子-1（vascular cell adhesion molecule-1,VCAM-1）和细胞间黏附分子-1（intercellular cell adhesion molecule-1,ICAM-1）]的影响。方法用MTS法测定不同浓度羟基红花黄素A对氧化损伤血管内皮细胞与U937细胞黏附率的影响,用反转录聚合酶链反应（RT-PCR）、酶联免疫吸附试验（ELISA）和Western法检测血管内皮细胞黏附分子的表达。结果羟基红花黄素A可以减轻血管内皮细胞与U937细胞的黏附,反转录聚合酶链反应、酶联免疫吸附试验和Western分析结果表明羟基红花黄素A减轻VCAM-1和ICAM-1的表达。结论羟基红花黄素A可通过减轻黏附分子ICAM-1,VCAM-1的表达,抑制白细胞与血管内皮细胞之间的黏附,从而预防氧化对内皮细胞的损伤。     

羟基红花黄色素A通过MAPK/ERK信号通路对去卵巢骨质疏松大鼠骨组织损伤的保护作用

目的 探究羟基红花黄色素(HSY)A通过丝裂原活化蛋白激酶(MAPK)/细胞外信号调节激酶(ERK)信号通路对去卵巢骨质疏松(OP)大鼠骨组织损伤的保护作用。方法 将SD大鼠分为假手术组、模型组、阿仑磷酸钠组(1.5 mg/kg阿仑磷酸钠)、HSYA-L组(2.5 mg/kg HSYA)、HSYA-M组(5 mg/kg HSYA)和HSYA-H组(10 mg/kg HSYA),每组10只,切除卵巢构建绝经后OP(PMOP)大鼠模型,术后1 w阿仑磷酸钠组、HSYA-L组、HSYA-M组、HSYA-H组分别灌胃相应剂量药物,假手术组、模型组灌胃等量生理盐水;双能X线吸收扫描仪检测大鼠骨密度(BMD);酶联免疫吸附试验(ELISA)检测大鼠血清中核因子κB受体活化因子配体(RANKL)和骨保护素(OPG)含量;测定骨组织生物力学指标;苏木素-伊红(HE)染色观察骨组织病理学情况;实时荧光定量PCR检测骨组织RANKL和OPG mRNA表达水平;Western印迹检测骨组织MAPK/ERK通路蛋白表达水平。结果 与假手术组相比,模型组股骨上下端及股骨BMD、血清OPG含量及mRNA表达水平、...     

红芪多糖对急性心肌梗死大鼠心肌氧化损伤及ERK/Nrf2/HO-1通路的影响

目的:探讨红芪多糖对急性心肌梗死（AMI）大鼠心肌氧化损伤及细胞外信号调节激酶/核因子E2相关因子2/血红素氧合酶-1（ERK/Nrf2/HO-1）通路的影响。方法：采用冠状动脉左前降支结扎法建立AMI大鼠模型,根据随机数字表法将72只雄性大鼠随机分为假手术组（只开胸不结扎）、模型组、阳性对照组（12mg/kg倍他乐克）、低、中、高剂量 [50、100、200mg/(kg·d)]红芪多糖组,每组12只,连续给药31d。给药结束后,采用全自动生化分析仪检测大鼠血清肌酸激酶同工酶（CK-MB）、心肌肌钙蛋白T（cTnT）和心肌肌钙蛋白I（cTnI）水平,酶联免疫法检测心肌组织丙二醛（MDA）含量、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSP-Px）活性,Western blot法检测磷酸化细胞外信号调节激酶（p-ERK）、核因子E2相关性因子2（Nrf2）、血红素氧合酶1（HO-1）、谷胱甘肽半胱氨酸连接酶催化亚基（GCLC）表达水平。结果：与假手术组相比,模型组大鼠血清CK-MB、cTnI和cTnT水平均显著升高（均P<0.05）,心肌组织MDA含量显著升高（P<0.05）,SOD和GSP-Px活力显著降低（均P<0.05）,p-ERK、Nrf2、HO-1、GCLC蛋白表达显著降低（均P<0.05）。与模型组相比,中、高剂量红芪多糖组大鼠血清CK-MB、cTnI和cTnT水平均显著降低（均P<0.05）,心肌组织MDA含量显著降低（P<0.05）,SOD和GSP-Px活力显著升高（均P<0.05）,p-ERK、Nrf2、HO-1、GCLC蛋白表达显著升高（均P<0.05）。结论：红芪多糖可能通过激活ERK/Nrf2/HO-1信号传导通路改善AMI大鼠心肌氧化损伤。     

益母草碱抑制ERK/NF-κB信号通路对心力衰竭大鼠心肌细胞凋亡的影响

目的:观察益母草碱抑制细胞外调节蛋白激酶(ERK)/核转录因子κB(NF-κB)信号通路对心力衰竭(HF)大鼠心肌细胞凋亡的影响。方法:将大鼠随机分为Control组、HF组,低剂量益母草碱(L-益母草碱)组、高剂量益母草碱(H-益母草碱)组及ERK抑制剂组。采用腹腔注射阿霉素法建立HF模型,HF模型建立成功后根据分组进行给药干预,连续14 d。利用彩色多普勒动物超声仪测量心功能指标[左室射血分数(LVEF)、左室收缩末期内径(LVESD)、左室舒张末期内径(LVEDD)、左室短轴缩短率(LVFS)]变化;末端脱氧核苷酸转移酶介导的dUTP缺口末端标记测定法(TUNEL)检测心肌细胞凋亡情况;免疫组化法检测心肌组织凋亡相关蛋白表达情况;蛋白免疫印迹法(Western Blot)检测心肌组织ERK/NF-κB信号通路相关蛋白表达情况。结果:与Control组比较,HF组LVEF、LVFS及心肌组织Bcl-2蛋白表达均减少,LVESD、LVEDD、心肌细胞凋亡率及心肌组织Bax蛋白表达均增加(P<0.05);与HF组比较,L-益母草碱组、H-益母草碱组、ERK抑制剂组LVEF、LVF...     

虎杖苷对急性脑梗死小鼠脑组织ERK1/2信号通路的影响

目的 探究虎杖苷对急性脑梗死(ACI)小鼠脑组织细胞外调节蛋白激酶(ERK)1/2信号通路的影响。方法 将65只SD小鼠随机分为sham组、ACI组、低剂量组、高剂量组、高剂量+抑制剂组各13只。采用改良的Zea Longa法构建ACI模型,sham组暴露、分离颈动脉,线栓未插入颈动脉;低剂量组、高剂量组、高剂量+抑制剂组分别每天腹腔注射相应剂量药物,sham组、ACI组注射等量生理盐水;对小鼠进行神经功能缺损评分(mNSS);氯化三苯基四氮唑(TTC)染色法检测小鼠脑梗死体积;苏木素-伊红(HE)染色观察脑组织病理学变化;检测脑组织含水量;原位末端转移酶标记技术(TUNEL)检测脑组织皮质细胞凋亡情况;Western印迹法检测凋亡及ERK1/2通路相关蛋白表达情况。结果 与sham组相比,ACI组mNSS评分、脑梗死体积、组织病变程度、脑组织含水量、细胞凋亡率、半胱氨酸天冬氨酸蛋白水解酶(Caspase)-3和B细胞淋巴瘤(Bcl)-2相关X蛋白(Bax)表达水平显著增加,而Bcl-2、p-ERK1/2/ERK1/2表达水平显著降低(P<0.05);与ACI组相比,低剂量组和高...     

青蒿琥酯对糖尿病大鼠MEK/ERK通路及心肌纤维化的影响

目的:探索青蒿琥酯对糖尿病大鼠丝裂原细胞外信号调节激酶(MEK)/细胞外信号调节激酶(ERK)通路及心肌纤维化的影响。方法:制作糖尿病大鼠模型,随机分为模型组、青蒿琥酯低剂量(25 mg/kg)组、青蒿琥酯中剂量(50 mg/kg)组、青蒿琥酯高剂量(100 mg/kg)组、二甲双胍(70 mg/kg)组,每组12只,另取12只SD大鼠设为对照组。分组处理后,测定大鼠血糖、总胆固醇(TC)及三酰甘油(TG)水平;Masson染色检测大鼠心肌组织纤维化情况;酶联免疫吸附法(ELISA)检测大鼠血清肌酸激酶同工酶(CK-MB)、肌钙蛋白I(cTnI)、肿瘤坏死因子-α(TNF-α)及白细胞介素-6(IL-6)水平;蛋白免疫印迹法检测心肌组织MEK/ERK通路相关蛋白表达。结果:与对照组比较,模型组大鼠心肌呈现明显纤维化变性,大鼠血糖、TC、TG、CK-MB、cTnI、TNF-α、IL-6水平及心肌组织MEK/ERK通路蛋白p-MEK/MEK、p-ERK/ERK明显升高(P<0.05)。与模型组比较,青蒿琥酯低剂量组、青蒿琥酯中剂量组、青蒿琥酯高剂量组及二甲双胍组大鼠心肌组织纤维化程度...     

茯苓酸对银屑病小鼠皮损组织IRS-1/ERK1/2通路及角质形成细胞增殖的影响

目的 探讨茯苓酸(PA)对银屑病小鼠皮损组织胰岛素受体底物(IRS)-1/细胞外调节蛋白激酶(ERK)1/2通路及角质形成细胞增殖的影响。方法 将BALB/C雄性小鼠随机分为正常对照组、模型组、PA低、中、高(1.25、2.50、5.00 mg/kg)剂量组、阳性药物组(氨甲蝶呤,2 mg/kg),每组10只。除正常对照组外,其余各组于背部涂抹5%咪喹莫特乳膏建立银屑病模型;各组均在分组后当天开始给药,PA各剂量组及阳性药物组灌胃给予相应剂量的PA和氨甲蝶呤,正常对照组和模型组灌胃给予相应体积生理盐水,连续给药1 w, 1次/d。各组末次给药24 h后,观察各组背部皮肤组织,并对银屑病皮损面积和严重程度指数(PASI)进行评分;取背部皮损组织,采用苏木素-伊红(HE)染色观察皮肤组织形态学改变;取血液和皮损组织,用酶联免疫吸附试验检测空腹胰岛素(FINS)、空腹血糖(FBG)水平及皮损组织炎性因子白细胞介素(IL)-6、肿瘤坏死因子(TNF)-α、IL-17、IL-23含量,计算胰岛素抵抗指数(HOMA-IR);Western印迹检测皮损组织IRS-1、ERK1/2、磷酸化ERK1/2...     

红景天苷对高海拔缺氧条件下大鼠心肌自噬相关通路AMPK的影响

目的 探讨红景天苷保护高海拔缺氧损伤大鼠心脏的可能分子机制。方法 将40只Wistar大鼠随机分为5组：空白对照组（1 500 m）、缺氧生理盐水组（6 500 m+NS）、缺氧Compound C组（6 500 m+comC）、缺氧红景天苷组（6 500 m+Sal）、缺氧红景天苷+Compound C组（6 500 m+comC+Sal）。造模完成后进行血气分析、HE染色、荧光TUNEL检测及Western blot检测。结果 (1)缺氧后大鼠心肌结构发生变化,心肌凋亡加重（P<0.05）,红景天苷治疗可改善心肌细胞病理性损伤,减少心肌细胞凋亡（P<0.05）;(2)缺氧后磷酸化AMPK水平上升,磷酸化mTOR水平降低（P<0.05）。而Compound C组AMPK及mTOR表现呈相反趋势,红景天苷治疗后AMPK及mTOR的表达水平介于Compound C组与红景天苷组之间,但是自噬蛋白Beclin-1的表达较Compound C组增加（P<0.05）。结论 红景天苷可以正向调节AMPK信号通路激活自噬,对缺氧损伤的大鼠心脏起保护作用。     

阿托伐他汀对同型半胱氨酸诱导的心肌细胞MEK/ERK通路及心肌线粒体损伤的影响

目的探讨阿托伐他汀对同型半胱氨酸(Hcy)诱导的心肌细胞H9c2丝裂原细胞外信号调节激酶(MEK)/细胞外调节蛋白激酶(ERK)通路及心肌线粒体损伤的影响。方法细胞计数试剂盒8(CCK-8)检测不同浓度Hcy对H9c2细胞存活率的影响,筛选Hcy诱导浓度和时间。将诱导后的H9c2细胞分为模型组、5μmol/L阿托伐他汀组、10μmol/L阿托伐他汀组和15μmol/L阿托伐他汀组,另取正常H9c2细胞为对照组。流式细胞仪检测各组细胞凋亡率;JC-1法检测各组细胞线粒体膜电位的变化;DCFH-DA法检测各组细胞内活性氧(ROS)水平;酶联免疫吸附法(ELISA)检测各组细胞中丙二醛(MDA)、超氧化物歧化酶(SOD)和过氧化氢酶(CAT)含量;Western blot检测各组细胞MEK1/2和ERK1/2磷酸化水平。结果与对照组相比,2μmol/L Hcy可显著降低H9c2细胞存活率(P0.05),本研究使用2μmol/L Hcy处理24 h诱导H9c2细胞。与对照组相比,模型组H9c2细胞凋亡率、ROS水平、MDA含量显著升高(P0.05),线粒体膜电位、SOD、CAT含量及MEK1/2、ERK1/2磷酸化水平显著降低(P0.05);与模型组相比,5μmol/L阿托伐他汀组、10μmol/L阿托伐他汀组和15μmol/L阿托伐他汀组H9c2细胞凋亡率、ROS水平、MDA含量依次降低(P0.05),线粒体膜电位、SOD、CAT含量及MEK1/2、ERK1/2磷酸化水平依次升高(P0.05)。结论阿托伐他汀可能通过激活MEK/ERK通路降低Hcy诱导的H9c2细胞氧化应激反应,减轻心肌线粒体损伤。     

羟基红花黄色素A对缺血损伤脑组织蛋白质硝基化修饰的影响

目的研究羟基红花黄色素A(HSYA)对缺血损伤脑组织蛋白质硝基化修饰的影响。方法模拟体内蛋白质硝基化的2条主要途径,体外以BSA为底物,分为对照组及低、中、高干预组(以HSYA 0.01、0.1和1mmol/L干预),Western blot法检测HSYA对BSA硝基化水平的影响。另选SD大鼠45只,随机分为假手术组、模型组和治疗组(HSYA 10mg/kg),每组15只。后2组大鼠制作大脑中动脉闭塞再灌注模型,采用Western blot法、免疫组织化学法观察脑组织蛋白质硝基化水平及HSYA对硝基化修饰的影响;TTC染色观察脑梗死体积的改变。结果与对照组比较,低、中、高干预组蛋白质硝基化水平呈剂量依赖性地降低,以高干预组的抑制作用最明显,差异有统计学意义(P<0.05)。假手术组脑组织中3-硝基酪氨酸仅有少量表达,与假手术组比较,模型组表达明显增加,而治疗组表达较模型组显著下降,差异有统计学意义(P<0.05)。治疗组脑梗死体积较模型组减少48.86%(P<0.01)。结论 HSYA对缺血损伤脑组织蛋白质硝基化具有抑制作用,这可能是其脑缺血再灌注损伤保护作用的分子机制之一。     

细胞外信号调节激酶通路介导的自噬对七氟烷后处理大鼠心肌缺血再灌注的保护机制

目的研究七氟烷后处理(SP)对大鼠心肌缺血再灌注(I/R)损伤的保护作用,探讨细胞外信号调节激酶(ERK1/2)转导通路介导的自噬在其中的机制作用。方法成年雄性SD大鼠90只,建立急性大鼠心肌I/R损伤模型。随机分为6组:假手术组(Sham组)、I/R组、SP组、七氟烷正常对照组(Control组)、ERK1/2抑制剂PD98059组(PD组)、PD98059溶剂DMSO组(DMSO组),各15只。后5组缺血30min,再灌注4h。再灌注4h末提取心脏,用TTC法测定心肌梗死范围,用Western blot法检测Beclin-1、LC3Ⅱ/Ⅰ及P62蛋白表达水平。结果与I/R组比较,SP组心肌梗死范围减小[(35.7±10.1)%vs(56.4±12.3)%,P<0.05],LC3Ⅱ/Ⅰ、Beclin-1和P62蛋白表达下调(P<0.05);与SP组比较,PD组心肌梗死范围增加[(50.7±8.3)%vs(35.7±10.1)%,P<0.05],LC3Ⅱ/Ⅰ、Beclin-1和P62蛋白表达上调(P<0.05)。结论 SP减轻了大鼠心肌I/R损伤,其机制可能是通过激活ERK1/2信号转导通路,抑制再灌注期间自噬体清除的破坏,进而抑制再灌注期间细胞死亡。     

生长激素释放肽对心衰大鼠心肌细胞中ERK-P表达的影响

目的 研究大鼠慢性心衰时细胞外信号调节激酶(ERK-P)含量的变化以及生长激素释放肽(GHRP)对其的影响.方法 Wistar成年大鼠45只随机分为假手术组、模型组和治疗组,每组15只.采用结扎左冠状动脉前降支建立大鼠慢性心衰模型,假手术组只挤出心脏,不结扎冠状动脉;治疗组造模后给予GHRP尾静脉注射4 w,通过HE染色观察心衰大鼠心肌组织形态学变化、Western印迹法检测各组大鼠心肌细胞中ERK-P蛋白表达水平.结果 模型组与假手术组相比,左室峰压、左室压力最大上升和下降速率(±dp/dtmax)明显降低,心肌组织中ERK-P明显升高(P＜0.0l);治疗组与模型组相比,左室峰压、左室压力最大上升和下降速率(±dp/dtmax)明显增高,心肌组织中ERK-P较模型组明显降低(P＜0.01),与假手术组相比ERK-P升高(P＜0.05).结论 ERK -P在慢性心衰发生过程中起重要作用,GHRP可降低慢性心衰大鼠心肌细胞ERK-P含量,有保护和改善心衰大鼠心功能的作用.     

中药心康方对大鼠心力衰竭模型心肌胶原代谢的影响

目的观察中药心康方对大鼠心力衰竭模型心肌胶原代谢的影响。方法阿霉素腹腔注射法建立大鼠心力衰竭模型,随机分为对照组(10只)、模型组(9只)、心康方组(9只)和卡托普利组(9只)。Masson染色观察心肌胶原变化,Western blot检测心肌Ⅰ型、Ⅲ型胶原、转化生长因子β1(TGF-β1)、核因子κB的抑制蛋白(IκB)和p56的表达,Western blot和RT-q PCR分别检测心肌基质金属蛋白酶(MMP)-2、MMP-9、基质金属蛋白酶组织抑制因子(TIMP)-1和TIMP-2的蛋白和mRNA表达水平。结果与对照组比较,模型组大鼠心肌Ⅰ型和Ⅲ型胶原表达显著增加,胶原容积分数显著升高(均为P<0.01);TGF-β1和p56表达显著增加,IκB显著降低(均为P<0.05);MMP-2、MMP-9、TIMP-1和TIMP-2的蛋白和mRNA表达水平显著升高(P<0.01或P<0.05)。与模型组比较,心康方组和卡托普利组大鼠的心肌Ⅰ型和Ⅲ型胶原表达显著减少,胶原容积分数显著降低(均为P<0.01);TGF-β1和p56显著降低,IκB显著升高(均为P<0.05);MMP-2、MMP-9、TIMP-1和TIMP-2的蛋白和mRNA表达水平显著降低(P<0.01或P<0.05)。结论中药心康方可减轻心力衰竭大鼠的心肌胶原沉积,其机制可能与抑制核因子κB介导的TGF-β1上调有关。     

Effects of Kangdaxin on myocardial fibrosis in heart failure with preserved ejection fraction rats

BackgroundThis study aimed to explore the effects of Kangdaxin oral liquid on myocardial fibrosis in heart failure with preserved ejection fraction (HFpEF) rats.MethodsA total of 30 Sprague Dawley (SD) rats were randomly divided into 3 groups Sham operation group (Sham), HFpEF group (HFpEF), and HFpEF with drug intervention group (HFpEF + I). Rats in HFpEF + I group were given Kangdaxin oral liquid at a dose of 2.7 mL/(kg·d). After modeling or treatment, the value of E/A and E/e'' in each group of rats were measured by echocardiography. The N-terminal pro b-type natriuretic peptide (NT-proBNP) level was determined by enzyme-linked immunosorbent assay (ELISA). Heart weight/body mass index (Hw/W) and left ventricular weight/body mass index (LVw/W) were calculated after the rats were sacrificed; the transforming growth factor-β1 (TGF-β1) protein expression level in cardiac tissue was detected by western blot.ResultsCompared with sham group, the values of diastolic function item (E/A) and mitral annular early diastolic velocity (E/e'') in HFpEF group were significantly decreased, and the level of NT-proBNP was significantly increased (P<0.05). Compared with HFpEF group, the value of E/A and E/e'' in HF + I group were significantly increased, and the level of NT-proBNP was significantly decreased (P<0.05). Compared with sham group, the expression of TGF-β1 protein in heart tissue of HFpEF group were significantly increased (P<0.05). Compared with HFpEF group, the expression of TGF-β1 protein in HFpEF + I group were significantly decreased (P<0.05).ConclusionsKangdaxin oral liquid has protective effect on heart in HFpEF rats, which can reduce the protein expression of TGF-β1 in the heart tissue of HFpEF rats. This may be a possible mechanism to inhibit myocardial fibrosis and improve cardiac diastolic function.     

CRP对人外周血CD14+单核细胞Toll受体信号转导的影响

Objectives In this work,we explore the effect of atorvastatin on myocardial apoptosis and caspase-8 acti- vation after coronary microembolization(CME) in rats. Methods Fifty rats were randomly divided into five groups; the coronary microembolization(CME) group,the sham-operated (sham) control group,the gastric lavage control group, the atorvastatin lavage group,and the caspasse-8 inhibitor (N-acetyl-Ile-Glu-Thr-Asp-CHO,abbreviated as CHO) group,with 10 rats for each group.A microembolization ball was injected through the left ventricle for constructing the CME model.Animals in the sham control group were given an injection of physiological saline instead of the microembolization ball.Seven days before the operation,the atorvastatin group underwent gastric lavage with 20 mg/kg of atorvastatin once a day.Gastric lavage control animals underwent gastric lavage with an equivalent dose of physiological saline instead of the atorvastatin.Animals in the CHO group were given an intraperitoneal injection of 10 mg/kg of CHO 30 min before the operation.Six hours after the operation,cardiac ultrasonic detection was conducted on each group to measure the cardiac function indexes.TUNEL(Terminal-deoxynucleoitidyl transferase mediated dUTP nick end labeling) assays were used to measure myocardial apoptosis,and western blots were used to quantify the expression levels of activated caspase-3 and -8.Results(1) The echocardiographic parameters showed that,compared to the sham control animals,the left ventricular ejection fraction(LVEF) of the CME group was significantly decreased(P<0.05).In addition, cardiac sonography revealed a decrease in the left ventricular shortening fraction(FS) and cardiac output(CO), but an increase in the left ventricular end-diastolic dimension (LVEDd).Compared to the CME group,the atorvastatin and CHO groups exhibited significantly improved cardiac function (P<0.05).(2) When compared with the sham control,the myocardical apoptotic rate of the CME group,as well as the levels of activated caspase-3     

The role of ERK1/2 signaling pathway in coronary microembolization-induced rat myocardial inflammation and injury

Objectives In this work,we explore the effect of atorvastatin on myocardial apoptosis and caspase-8 acti- vation after coronary microembolization(CME) in rats. Methods Fifty rats were randomly divided into five groups; the coronary microembolization(CME) group,the sham-operated (sham) control group,the gastric lavage control group, the atorvastatin lavage group,and the caspasse-8 inhibitor (N-acetyl-Ile-Glu-Thr-Asp-CHO,abbreviated as CHO) group,with 10 rats for each group.A microembolization ball was injected through the left ventricle for constructing the CME model.Animals in the sham control group were given an injection of physiological saline instead of the microembolization ball.Seven days before the operation,the atorvastatin group underwent gastric lavage with 20 mg/kg of atorvastatin once a day.Gastric lavage control animals underwent gastric lavage with an equivalent dose of physiological saline instead of the atorvastatin.Animals in the CHO group were given an intraperitoneal injection of 10 mg/kg of CHO 30 min before the operation.Six hours after the operation,cardiac ultrasonic detection was conducted on each group to measure the cardiac function indexes.TUNEL(Terminal-deoxynucleoitidyl transferase mediated dUTP nick end labeling) assays were used to measure myocardial apoptosis,and western blots were used to quantify the expression levels of activated caspase-3 and -8.Results(1) The echocardiographic parameters showed that,compared to the sham control animals,the left ventricular ejection fraction(LVEF) of the CME group was significantly decreased(P<0.05).In addition, cardiac sonography revealed a decrease in the left ventricular shortening fraction(FS) and cardiac output(CO), but an increase in the left ventricular end-diastolic dimension (LVEDd).Compared to the CME group,the atorvastatin and CHO groups exhibited significantly improved cardiac function (P<0.05).(2) When compared with the sham control,the myocardical apoptotic rate of the CME group,as well as the levels of activated caspase-3 and-8,increased significantly (P<0.05).The myocardial apoptotic rate,as well as the levels of activated caspase-3 and caspase-8 in the atorvastatin and CHO groups,decreased significandy(P<0.05) in comparison to the CME group.Conclusions The atorvastatin pretreatment clearly suppressed post-CME myocardial apoptosis and improved cardiac function.The most likely mechanism for these effects is the blockade of the myocardial death receptor -mediated apoptosis pathway.     

曲美他嗪对慢性心力衰竭大鼠心肌能量代谢及超微结构的影响

目的研究曲美他嗪对异丙肾上腺素诱导的慢性心力衰竭大鼠心肌能量代谢和超微结构的影响。方法72只雄性SD大鼠随机分为对照组(14只)和模型组(58只),模型制备采用皮下多点注射异丙肾上腺素法,4周后模型组大鼠死亡12只,再将存活的46只模型组大鼠随机分为未治疗组(M组,16只)、曲美他嗪治疗组(T组,15只)和培哚普利治疗组(P组,15只)。治疗5周后行二维心脏超声检查和病理形态学观察,并测定心肌组织能量代谢相关指标。结果与M组比较,T组大鼠LVEF、左心室短轴缩短率均提高;光镜和电镜下观察T组和P组心肌损伤程度较M组明显减轻。T组与P组大鼠心肌二磷酸腺苷(ADP)、一磷酸腺苷、ATP/ADP和总腺苷含量与对照组比较差异无统计学意义(P>0.05)。T组大鼠心肌肌浆网Ca2+-ATPase活性与对照组和P组比较差异无统计学意义。结论曲美他嗪能够改善心力衰竭大鼠心肌能量代谢、病理和超微结构,并且有改善大鼠心功能的趋势。