阿托伐他汀对糖尿病大鼠急性心肌梗死后心功能及HGF/c-Met信号通路的影响*

 目的： 糖尿病患者急性心肌梗死（AMI）后的心室重构及心功能恶化较非糖尿病者更为明显。本研究旨在观察阿托伐他汀对糖尿病大鼠AMI后心肌细胞凋亡、心室重构及心功能的影响,并探讨其作用是否与肝细胞生长因子及其受体 (HGF/c-Met)信号通路有关。方法: 70只雄性SD大鼠经链脲霉素 (STZ, 65 mg/kg)腹腔注射,诱导糖尿病大鼠模型。8周后对糖尿病大鼠结扎左冠状动脉前降支构建AMI大鼠模型,术后存活32只大鼠随机分为2组：AMI对照组(n=16)和阿托伐他汀干预组(n=16, 阿托伐他汀20 mg·kg-1·d-1),并在糖尿病大鼠中设假手术组(n=11),术后24 h予以灌胃给药。2周后比较各组大鼠心功能、心肌组织病理改变、心肌细胞凋亡、HGF和c-Met mRNA及蛋白表达差异。结果: (1) AMI对照组心功能显著低于假手术组（P<0.05）,胶原容积分数、心肌细胞凋亡指数、HGF及c-Met mRNA及蛋白表达均显著高于假手术组（P<0.05）;(2) 阿托伐他汀干预组的胶原容积分数和心肌细胞凋亡指数显著低于AMI对照组（P<0.05）,心功能、HGF及c-Met mRNA及蛋白表达均显著高于AMI对照组（P<0.05）。结论: 阿托伐他汀对糖尿病大鼠AMI后心肌细胞凋亡、心室重构及心功能具有显著改善作用;HGF/c-Met信号通路在AMI后会激活,阿托伐他汀的上述作用机制可能与其进一步增强HGF/c-Met信号通路有关。     

阿托伐他汀联合丙泊酚治疗能够抑制NLRP3炎症小体缓解大鼠心肌缺血再灌注损伤

目的 探讨阿托伐他汀与丙泊酚联合治疗在大鼠心肌缺血再灌注损伤中的作用机制及其与NLRP3炎症小体之间的关系。方法 构建心肌细胞缺血再灌注模型;将大鼠随机分为假手术组（Sham）、模型组（MIRI）、阿托伐他汀组（Atorvastatin）、丙泊酚组（Propofol）和阿托伐他汀与丙泊酚联合组（Atorvastatin+Propofol）。应用TTC染色法检测各组大鼠心肌损伤面积;应用TUNEL染色法检测心肌细胞的凋亡情况;免疫荧光法检测ROS的表达水平;ELISA法检测心肌细胞中TNF-α、IL-6、IL-1β和IL-18的表达情况;应用Western blot法检测NLRP3、Caspase-1、IL-1β及GSDMD-N的变化。结果 与模型组相比,阿托伐他汀和丙泊酚联合治疗组中大鼠的心肌梗死面积降低显著降低（P<0.05）;心肌细胞的凋亡率显著降低（P<0.05）;ROS的水平显著下降（P<0.05）;TNF-α、IL-6、IL-1β和IL-18的表达明显下降（P<0.05）以及NLRP3、Caspase-1、IL-1β及GSDMD-N等蛋白的水平显著降低（P<0.05）。结论 阿托伐他汀与丙泊酚联合治疗能够降低心肌细胞的凋亡、氧化应激反应和炎症反应,其机制与下调NLRP3炎症小体及其相关的蛋白表达有关。     

阿托伐他汀对高血压大鼠肾脏CTGF表达的影响

目的:观察自发性高血压大鼠(SHR)肾脏结缔组织生长因子(CTGF)的表达,探讨3-羟基-3-甲基戊二酞辅酶A(HMG-CoA)还原酶抑制剂阿托伐他汀(Atorvastin)对高血压肾损害的保护作用。方法:20只12周龄雄性SHR随机分为阳性对照组和阿托伐他汀干预组各10只,药物干预组每只大鼠予以阿托伐他汀20mg/kg/天灌胃(共12周);10只12周龄雄性WKY大鼠作为正常对照组。测量不同时期各组大鼠尾动脉收缩压(SBP)、血脂、尿β2-微球蛋白(β2-MG)及肾功能指标;用免疫组织化学方法检测CTGF蛋白在各组大鼠肾脏中的表达;用RT-PCR方法检测CTGFmRNA在肾脏的表达水平。结果:⑴与正常对照组、药物干预组相比,阳性对照组血清尿素氮(BUN)、肌酐(Cr)水平无显著差异,而SBP、血脂、尿β2-MG均显著增高(P<0.01)。⑵CTGF蛋白及mRNA在阳性对照组肾脏中的表达较正常对照组明显增强,药物干预组比阳性对照组明显减少(P<0.05)。结论:CTGF表达增加可能是导致高血压肾损害的重要机制之一;阿托伐他汀通过降低血压及血脂,显著减少尿β2-MG,改善肾组织的病理变化,抑制CTGF在SHR肾脏表达而发挥对高血压肾损害的保护作用。     

阿托伐他汀对心肌梗死大鼠心肌细胞核内FoxO3a表达的影响

目的探讨阿托伐他汀对大鼠心肌梗死(myocardial infarction,MI)后心肌细胞核内FoxO3a表达和心室重构的影响。方法建立大鼠MI模型,24 h后存活大鼠随机分成MI组(n=8)、阿托伐他汀10 mg组[10 mg/(kg.d),Ato组,n=8],同时另设假手术组(Sham组,n=10)。4周后观察左心室质量指数(left ventricular mass index,LVMI),免疫组化染色和RT-PCR检测FoxO3a在左心室非梗死区(non-infarction zone,NIZ)心肌细胞核内蛋白质和mRNA表达水平,流式细胞技术(flow cytometry,FCM)检测FoxO3a蛋白在NIZ心肌细胞核内表达含量。SAS9.1统计软件分析数据。结果 MI组与Sham组相比,LVMI显著增加(P<0.05);左室心肌非梗死区FoxO3a mRNA、FoxO3a蛋白表达(免疫组化)、FCM检测心肌细胞核内蛋白表达量表达均降低(P<0.05)。与MI组相比,Ato组LVMI显著下降(P<0.05);但高于Sham组(P<0.05);与MI组比较Ato组左室心肌非梗死区FoxO3a mRNA、Fox-O3a蛋白表达(免疫组化)、FCM检测心肌细胞核内蛋白表达量表达均显著增高(P<0.05);但低于Sham组(P<0.05)。结论阿托伐他汀能够有效地改善MI后心室重构,机制可能与上调细胞核内FoxO3a表达量有关。     

Akt信号蛋白在阿托伐他汀作用于UUO大鼠肾小管-间质中的表达

目的： 探讨PI3K/Akt信号通路是否参与了阿托伐他汀延缓UUO大鼠肾小管-间质纤维化过程。方法: 将45只SD大鼠随机分为假手术组、模型组及阿托伐他汀治疗组（简称阿乐组）。模型组与阿乐组大鼠均行左侧输尿管梗阻（UUO）术。阿乐组于术前3 d开始阿托伐他汀（10 mg·kg^-1·d^-1）灌胃，其余两组予等量生理盐水灌胃。术后第5、10、15 d分别处死各组中的5只大鼠，取左肾行HE和Masson染色，并用免疫组化方法检测肾小管间质中TGF-β₁、Akt1、磷酸化Akt1的表达。结果: 模型组大鼠肾小管间质细胞增多，纤维化明显。阿乐组大鼠肾小管间质病变程度较同期模型组明显减轻（P<0.05）。模型组大鼠梗阻肾小管-间质中Akt1、磷酸化Akt1、TGF-β₁表达较假手术组明显增加（P<0.01），Akt1活性增加（P<0.01）。阿乐组大鼠上述指标在肾小管-间质的表达程度均较同期模型组明显减轻（P<0.05）。梗阻肾术后第5 d和第15 d肾组织Akt1活性与TGF-β₁表达呈正相关（r=0.63, P<0.05；r=0.64, P<0.05）。结论: 阿托伐他汀可减少输尿管梗阻后磷酸化Akt1、总的Akt1、TGF-β₁的表达，抑制Akt1活性，提示PI3K/Akt信号通路可能参与了阿托伐他汀延缓UUO大鼠肾小管-间质纤维化的过程。     

阿托伐他汀对急性心梗大鼠心肌血管新生及eNOS及RhoA表达的影响

目的观察不同剂量阿托伐他汀对急性心梗大鼠心肌血管新生及心肌eNOS及RhoA表达的影响。方法雄性急性心肌梗死大鼠60只,随机分为四组,即小剂量阿托伐他汀(3 mg.kg-1.d-1)组、中剂量阿托伐他汀(12 mg.kg-1.d-1)组、大剂量阿托伐他汀(50 mg.kg-1.d-1)组、对照组,每组15只。每只给予连续灌胃2周,对照组给予生理盐水。2周后处死动物,α-SMA及vWF免疫组化染色检测心肌血管密度;逆转录-聚合酶链反应法(RT-PCR)检测内皮型一氧化氮合酶(eNOS)及RhoA mRNA的表达。结果大剂量组α-SMA染色阳性血管计数较对照组明显减少,有极显著性差异(P<0.01);中剂量组vWF染色阳性微血管计数较对照组明显增加,有极显著差异(P<0.01)。中剂量组eNOS mRNA表达较对照组明显增加,有显著性差异(P<0.05)。大剂量组RhoA mRNA表达较对照组明显减少,有显著性差异(P<0.05)。结论阿托伐他汀对大鼠急性心肌梗死后心肌血管新生的作用与剂量有关。eNOS、RhoA可能参与阿托伐他汀对急性梗死心肌血管新生作用过程。     

阿托伐他汀对自发性高血压大鼠血压、循环和心肌血管紧张素Ⅱ水平的影响

目的：观察阿托伐他汀对自发性高血压大鼠（SHR）血压、循环和心肌血管紧张素Ⅱ(Ang Ⅱ)水平的影响。 方法: 24只SHR随机分为4组（每组6只）：SHR对照组、阿托伐他汀50 mg组、阿托伐他汀10 mg组和缬沙坦组, 6只WKY大鼠作为正常血压对照组（WKY组）。给药前和给药后每两周测量大鼠尾动脉收缩压（SBP）。测定血清脂质及血浆和心肌血管紧张素Ⅱ（AngⅡ）水平。 结果: SHR各组SBP于给药前无显著差异（P>0.05），但均显著高于WKY组（P<0.01）；给药后第4、6周,阿托伐他汀50 mg组SBP明显低于SHR对照组（P<0.01）,10 mg组则不明显；缬沙坦组自给药后第2周，SBP进行性下降（P<0.01）。SHR对照组与WKY组血脂各项指标无显著差异（P>0.05）；阿托伐他汀50 mg组TC、TG及LDL-C水平明显低于SHR对照组（P<0.05，P<0.01），10mg组仅LDL-C水平明显下低于SHR对照组（P<0.05）。SHR对照组血浆AngⅡ浓度无明显差异，但心肌AngⅡ浓度明显高于WKY组（P<0.05）；给药6周后，阿托伐他汀各剂量组和缬沙坦组血浆AngⅡ浓度显著高于SHR对照组（均P<0.01），而心肌AngⅡ浓度在阿托伐他汀50 mg组和缬沙坦组明显低于SHR对照组（P<0.05）。 结论: 阿托伐他汀能降低SHR的血压，机制可能与降低心肌AngⅡ浓度含量有关。     

高脂血症大鼠主动脉HSP22、TNF-α和eNOS的表达及阿托伐他汀的影响

 目的:研究高脂血症大鼠主动脉热休克蛋白22（HSP22）、肿瘤坏死因子 α（TNF-α）及内皮型一氧化氮合酶（eNOS）的表达,以及阿托伐他汀对其的影响。方法:复制高脂血症大鼠模型后,实验分为正常对照组、高脂对照组和高脂+阿托伐他汀干预组。免疫组化法检测大鼠主动脉HSP22及TNF-α表达,Western blotting检测eNOS蛋白表达。结果:正常对照组未见HSP22和TNF-α阳性表达;高脂对照组与他汀干预组可见HSP22和TNF-α阳性表达;他汀干预组HSP22和TNF-α平均吸光度值明显低于高脂对照组（0.211±0.014 vs0.345±0.042,0.218±0.090 vs0.377±0.094,均P<0.05）。高脂对照组和他汀干预组eNOS表达均较正常对照组明显降低(P<0.01),高脂对照组和他汀干预组差异无显著。结论: HSP22和TNF-α在高脂血症大鼠主动脉中的表达升高,而eNOS的表达降低,阿托伐他汀的干预可降低HSP22和TNF-α的表达,但未能改变eNOS的表达。     

阿托伐他汀对实验性自身免疫性心肌炎MHCⅡ类分子表达的调节作用

目的探讨阿托伐他汀对实验性自身免疫性心肌炎（experimental autoimmune myocarditis,EAM）的作用及对心肌MHCⅡ类分子表达的影响.方法以纯化猪心肌肌球蛋白免疫Lewis大鼠诱导EAM模型.随机分为阿托伐他汀治疗组和未治疗组.治疗组给予阿托伐他汀每天10 mg/kg,未治疗组给予等体积饮用水,分别以灌胃器给药,连续用药3周.以未免疫的同周龄Lewis大鼠为正常对照组.用药21 d后,检测超声心动图,脾T淋巴细胞增殖试验、HE染色观察心肌组织炎症浸润程度,免疫组化检测心肌内CD4＋或CD8＋T细胞的浸润及心肌组织MHCⅡ类分子的表达.RT-PCR检测心肌Ⅰ型、Ⅲ型及Ⅳ型MHCⅡ类分子转录活化因子（classⅡ transactivator,CⅡTA）启动子转录.结果阿托伐他汀显著改善EAM大鼠心功能,治疗组心肌组织炎症浸润减轻,MHCⅡ类分子表达减少,抗原诱导的T淋巴细胞增殖显著受抑制.Ⅳ型CⅡTA启动子表达下调,而Ⅰ、Ⅲ型CⅡTA启动子表达与未治疗组比较差异无统计学意义.结论阿托伐他汀显著改善EAM大鼠心功能及组织病理学表现,其机制可能通过下调Ⅳ型CⅡTA启动子转录,抑制心肌非专职性APC MHCⅡ类分子表达.表明他汀类对EAM具有免疫调节效应,从而在器官特异性自身免疫性心肌损伤的治疗中具有应用前景.     

氟伐他汀对缺血再灌注损伤兔心肌细胞间粘附分子的影响

目的:探讨氟伐他汀短期预处理对缺血再灌注损伤兔心肌的保护作用及其机制。方法:日本大耳白兔21只随机分为3组:①假手术对照组(Sham组),②缺血再灌注组(IR组),③氟伐他汀干预组(F组)。实验中持续监测左室收缩压(LVSP)、左室舒张末压(LWEDP)、左室内收缩压最大上升速率和下降速率(±dp/dtmax)的变化,再灌注结束后用伊文氏蓝和TTC染色法确定缺血和梗死心肌范围,用RT-PCR进行心肌局部ICAM-1 mRNA表达测定。结果:缺血再灌注后,F组上述心功能各项指标较IR组明显改善,心肌组织ICAM-1 mRNA水平较IR组显著降低;心肌梗死面积较IR组明显减小。结论:氟伐他汀短期预处理可降低心肌缺血再灌注后心肌ICAM-1 mRNA表达,降低心肌梗死程度,改善心功能,对心肌缺血再灌注损伤有明显的保护作用。     

α-亚麻酸减轻糖尿病大鼠心肌缺血/再灌注损伤

 目的 研究摄食?-亚麻酸（ALA）对糖尿病大鼠心肌缺血/再灌注（MI/R）损伤的影响。方法 构建高脂饲料-链脲霉素诱导的2型糖尿病大鼠模型（HFD-STZ）,每日灌胃给予正常或HFD-STZ大鼠ALA处理（500 μg/kg）,4周后行心肌缺血（30 min）/再灌注（4或6 h）,并检测心肌梗死范围、血清肌酸激酶（CK）、乳酸脱氢酶（LDH）活性、细胞凋亡,用Western blot检测PI3K、Akt等。结果 HFD-STZ大鼠MI/R损伤加重,虽摄食ALA 4周对正常动物MI/R损伤无影响,但可将HFD-STZ大鼠的心梗面积减小至37.7% ± 5.4%,显著低于对照组的45.6% ± 8.5%（P < 0.05）,且血清CK、LDH活性及细胞凋亡减少;还可增加HFD-STZ大鼠心肌PI3K表达及Akt磷酸化。结论 长期摄食ALA有效减轻糖尿病大鼠MI/R损伤,可能与激活PI3K-Akt信号有关。     

Time course of hydrogen peroxide-thioredoxin balance and its influence on the intracellular signalling in myocardial infarction

We investigated the myocardial thioredoxin-1 and hydrogen peroxide concentrations and their association with some prosurvival and pro-apoptotic proteins, during the transition from myocardial infarction (MI) to heart failure in rats. Male Wistar rats were divided into the following six groups: three sham-operated groups and three MI groups, each at at 2, 7 and 28 days postsurgery. Cardiac function was analysed by echocardiography; the concentration of H(2)O(2) and the ratio of reduced to oxidized glutathione were measured spectrophotometrically, while the myocardial immunocontent of thioredoxin-1, angiotensin II, angiotensin II type 1 and type 2 receptors, p-JNK/JNK, p-ERK/ERK, p-Akt/Akt, p-mTOR/mTOR and p-GSK3β/GSK3β was evaluated by Western blot. Our results show that thioredoxin-1 appears to make an important contribution to the reduced H(2)O(2) concentration. It was associated with lower JNK expression in the early period post-MI (2 days). However, thioredoxin-1 decreased, while renin-angiotensin system markers and levels of H(2)O(2) increased, over 28 days post-MI, in parallel with some signalling proteins involved in maladaptative cardiac remodelling and ventricular dysfunction. These findings provide insight into the time course profile of endogenous antioxidant adaptation to ischaemic injury, which may be useful for the design of therapeutical strategies targeting oxidative stress post-MI.     

Functional Effects of WNT1-Inducible Signaling Pathway Protein-1 on Bronchial Smooth Muscle Cell Migration and Proliferation in OVA-Induced Airway Remodeling

Upregulation of WISP1 has been demonstrated in lung remodeling. Moreover, it has been recently found that some signaling components of WNT pathway can activate GSK3β signaling to mediate remodeling of airway smooth muscle (ASM) in asthma. Therefore, we hypothesized that WISP1, a signaling molecule downstream of the WNT signaling pathway, is involved in PI3K/GSK3β signaling to mediate ASM remodeling in asthma. Our results showed that WISP1 depletion partly suppressed OVA-induced ASM hypertrophy in vivo. In vitro, WISP1 could induce hBSMC hypertrophy and proliferation, accompanied by upregulation of levels of PI3K, p-Akt, p-GSK3β, and its own expression. TGF-β treatment could increase expression of PI3K, p-Akt, p-GSK3β, and WISP1. SH-5 treatment could partly suppress TGF-β-induced hypertrophy and proliferation of hBSMC, and depress expression of p-GSK3β and WISP1. In conclusion, WISP1 may be a potential inducer of ASM proliferation and hypertrophy in asthma. The pro-remodeling effect of WISP1 is likely due to be involved in PI3K-GSK3β-dependent noncanonical TGF-β signaling.     

Cardiac oxidative stress and remodeling following infarction: role of NADPH oxidase

BackgroundThere is growing recognition that oxidative stress plays a role in the pathogeneses of myocardial repair/remodeling following myocardial infarction (MI). Nicotinamide adenine denucleotide phosphate (NADPH) oxidase is a major source for cardiac reactive oxygen species production. Herein, we studied the importance of NADPH oxidase in development of cardiac oxidative stress and its induced molecular and cellular changes related to myocardial repair/remodeling.MethodsMI was created by coronary artery ligation in C57/BL (wild type) and NADPH oxidase (gp91^phox) knockout mice. Cardiac oxidative stress, inflammatory/fibrogenic responses, apoptosis, and hypertrophy were detected by in situ hybridization, immunohistochemistry, terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL), picrosirius red staining, and image analysis, respectively, at different stages post MI.ResultsIn wild-type mice with MI, and compared to sham-operated animals, we observed significantly increased gp91^phox and 3-nitrotyrosine, a marker of oxidative stress, in the infarcted myocardium; accumulated macrophages and myofibroblasts at the infarct site; abundant apoptotic myocytes primarily at border zones on Day 3; and numerous apoptotic inflammatory/myofibroblasts in the later stages. In addition, we detected significantly increased transforming growth factor β1, tissue inhibitor of metalloprotease 2, and type 1 collagen gene expression; continuously increasing collagen volume in the infarcted myocardium; and hypertrophy in noninfarcted myocardium. Compared to wild-type mice with MI, we did not observe significant difference in infarct size/thickness, cardiac hypertrophy, myocyte apoptosis, inflammatory/fibrogenic responses, as well as cardiac oxidative stress in gp91^phox knockout mice.ConclusionOur findings indicate that during NADPH oxidase deficiency, superoxide production can be compensated by other sources, which leads to cardiac oxidative stress and its related molecular/cellular events in the infarcted heart.     

心肌梗死大鼠缺血心肌中内皮抑素的表达

目的： 观察心肌梗死后大鼠不同时间缺血心肌中内皮抑素的表达及其与新生血管密度和血管内皮生长因子（VEGF）的关系。 方法： 32只心肌梗死SD大鼠随机分为心肌梗死后7、14、21、28 d 4个组，以假手术组作为正常对照组，每组8只。应用免疫组织化学染色方法，观察各组心肌梗死大鼠缺血心肌中内皮抑素、VEGF 的表达和新生血管密度。 结果： 心肌梗死大鼠缺血心肌中内皮抑素的表达明显增加，弥散分部于心肌细胞和组织间隙，第7 d表达量最高，至14、21、28 d表达量逐渐降低，28 d基本降至基础水平，与VEGF表达的变化趋势一致，并与新生血管密度相关。 结论： 内皮抑素在心肌梗死大鼠的缺血心肌中表达增加，与VEGF的动态变化一致，并与新生血管密度呈正相关，提示内皮抑素可能参与缺血心肌血管新生的调节。     

Intracoronary delivery of DNAzymes targeting human EGR-1 reduces infarct size following myocardial ischaemia reperfusion

Despite improvements in treatment, myocardial infarction (MI) remains an important cause of morbidity and mortality. Inflammation arising from ischaemic and reperfusion injury is a key mechanism which underpins myocardial damage and impairment of cardiac function. Early growth response-1 (Egr-1) is an early immediate gene and a master regulator that has been implicated in the pathogenesis of ischaemia-reperfusion (IR) injury. This study sought to examine the effect of selective inhibition of Egr-1 using catalytic deoxyribonucleic acid molecules (DNAzymes, DZs) delivered via the clinically relevant coronary route in a large animal model of myocardial IR. It was hypothesized that Egr-1 inhibition with intracoronary DZ would reduce infarction size by modulating its downstream effector molecules. Egr-1 DZs inhibited the adherence of THP-1 monocytes to IL-1β-activated endothelial cells in vitro and retained its catalytic activity up to 225 min after in vivo administration. In a porcine model of myocardial IR (45 min ischaemia/3 h reperfusion), DZ was taken up in the cytoplasm and nuclei of cardiomyocytes and endothelial cells in the myocardium after intracoronary delivery. Egr-1 DZs reduced infarct size and improved cardiac functional recovery following intracoronary delivery at the initiation of IR in this large animal model of MI. This was associated with inhibition of pro-inflammatory Egr-1 and ICAM-1 expression, and the reduced expression of TNF-α, PAI-1, TF, and myocardial MPO activity in tissue derived from the border zone of the infarct. Taken together, these data suggest that strategies targeting Egr-1 via the intracoronary route after IR injury in pigs have potential therapeutic implications in human MI.     

GYY4137 protects against myocardial ischemia and reperfusion injury by attenuating oxidative stress and apoptosis in rats

Hydrogen sulfide（H₂S） is a gasotransmitter that regulates cardiovascular functions.The present study aimed to determine the protective effect of slow-releasing H₂S donor GYY4137 on myocardial ischemia and reperfusion（I/R） injury and to investigate the possible signaling mechanisms involved.Male Sprague-Dawley rats were treated with GYY4137 at 12.5 mg/（kg·day）,25 mg/（kg·day） or 50 mg/（kg·day） intraperitoneally for7 days.Then,rats were subjected to 30 minutes of left anterior descending coronary artery occlusion followed by reperfusion for 24 hours.We found that GYY4137 increased the cardiac ejection fraction and fractional shortening,reduced the ischemia area,alleviated histological injury and decreased plasma creatine kinase after myocardial I/R.Both H₂S concentration in plasma and cystathionine-γ-lyase（CSE） activity in the myocardium were enhanced in the GYY4137 treated groups.GYY4137 also decreased malondialdehyde and myeloperoxidase levels in serum,attenuated superoxide anion level and suppressed phosphorylation of mitogen activated protein kinases in the myocardium after I/R.Meanwhile,GYY4137 increased the expression of Bcl-2 but decreased the expression of Bax,caspase-3 activity and apoptosis in the myocardium.The data suggest that GYY4137 protects against myocardial ischemia and reperfusion injury by attenuating oxidative stress and apoptosis.     

芪苈强心对心肌梗死后大鼠心肌细胞凋亡的影响

目的: 探讨芪苈强心对心肌梗死大鼠心肌细胞凋亡的影响。方法: 结扎冠脉前降支制作大鼠心肌梗死模型,随机分为假手术组(sham, n=5)、心肌梗死组(MI, n=16)和芪苈强心组(4 g·kg^-1·d^-1, n=15),28 d后检测心肌梗死面积,TUNEL法检测心肌细胞凋亡指数(AI),免疫组化法检测Fas蛋白表达,Western blotting检测黄嘌呤氧化酶(XO)和caspase-3蛋白表达,比色法测定XO和清除活性氧活性。结果: MI组非梗死区心肌细胞AI升高,Fas、XO和caspase-3蛋白表达增强,XO活性增加,清除活性氧活性降低(P<0.01)。芪苈强心组与MI组比较,非梗死区心肌细胞AI降低,Fas和caspase-3蛋白表达减少,XO活性降低,清除活性氧活性升高(P<0.01),但梗死面积和XO蛋白表达在两组间无显著差异(P>0.05)。结论: 芪苈强心能够抑制非梗死区心肌细胞凋亡,其作用机制可能与减少活性氧簇生成及降低Fas和caspase-3的表达有关。