大鼠自主呼吸下建立急性心肌梗死模型

目的大鼠自主呼吸情况下,快捷、简便地建立大鼠急性心肌梗死模型。方法 180～220gSD大鼠60只,于胸骨左缘第4-5肋间隙切开皮层作荷包缝合,逐层钝性分离肌肉,挤出心脏,快速结扎左冠状动脉前降支(LAD)后,送回心脏同时挤压胸廓,拉紧荷包以建立心肌梗死模型。记录结扎前、结扎后3h心电图;结扎3h后取出心脏,冰冻切片TTC染色。结果 50只大鼠成功建立心肌梗死模型,模型成功率为83.33%。心电图显示结扎冠脉后出现R波峰降低,ST段拱背抬高及ST-T融合,TTC染色后左心室出现明显灰白色梗死区。结论本方法可在大鼠自主呼吸情况下,较短的时间内以简便的手术、较小的创伤建立大鼠急性心肌梗死模型。     

大鼠心肌梗死模型构建和评价方法的改良

目的 优化和改良大鼠心肌梗死模型的构建和评价方法,提高模型的可靠性和稳定性.方法 取雄性SD大鼠结扎左冠状动脉前降支建立心肌梗死模型,在模型的构建过程中从麻醉、插气管、保温、手术操作、术后护理等环节进行优化和改进,并观察不同的麻醉方法和术后时间对心肌梗死程度的影响,用不同的染色方式进行心肌梗死模型的评价.结果 对比大鼠心肌梗死模型构建过程中各组大鼠麻醉时间、术后恢复以及心肌梗死面积的结果,戊巴比妥钠是更合适的麻醉药;结扎手术后时间对模型心肌梗死范围无明显影响（P＆gt;0.05）,但心肌缺血危险区面积随术后时间的延长明显减少（P〈0.01）;TTC与依文思蓝双重染色相对TTC染色能明显观察到心肌缺血危险区和梗死区范围.结论 优化和改进后的大鼠心肌梗死模型,提高了动物福利,制备和评价方法更加客观准确.     

急性正后壁心肌梗死心电图表现及临床意义

急性心肌梗死的早期诊断是临床上早期溶栓治疗的关键。急性正后壁心肌梗死临床上并非少见．但因常规12导联心电图上不呈现心肌梗死典型表现,常易被漏诊,错过了最佳溶栓时机。因此,当胸痛时V1—3导联ST段压低则可作为其早期的心电图特征。从1995～2003年,我院收治急性正后壁心肌梗死患者14例,现对其心电图表现及临床意义进行分析。     

单侧输尿管结扎再通大鼠模型的建立方法及其评价

目的比较单侧输尿管结扎（UUO）与单侧输尿管结扎再通（RUUO）建立的SD大鼠肾纤维化模型的优劣,从而得到更符合临床慢性肾衰进展特点的动物模型,以供临床药物筛选、疗效评介、科研、教学使用。方法健康SPF级雄性SD大鼠54只,随机分成假手术组、UUO组及UUO再通组各18只,造模成功后检测血肌酐（Scr）、尿素氮（BUN）及尿N-乙酰-β-D-氨基葡萄糖苷酶（NAG）,病理检查肾小管间质纤维化指数和免疫组化检查α-肌动蛋白（α-SMA）。结果无论从肾功能方面,还是病理检查方面,UUO再通的大鼠肾纤维化动物模型均优于UUO大鼠模型。结论再通UUO肾纤维化大鼠模型在功能及病理方面及其相关的免疫组化方面优于UUO组,其病理特点更符合慢性肾小管间质纤维化进程的动物模型。     

急性大鼠心肌梗死实验模型的制备

目的建立一种稳定可重复的急性心肌梗死动物模型。方法Wistar大鼠经戊巴比妥钠麻醉后,气管切开插管,连通呼吸机,开胸后结扎左冠状动脉前降支。4周后取出心脏做病理组织学和心肌特异性肌钙蛋白T免疫组织化学染色检测。结果成功制备心肌梗死动物模型,并进行了病理组织学和免疫组织化学染色证实。结论本建立的实验方法操作简单,成功率高,结果可靠。     

液氮冷冻大鼠左冠状动脉前降支中上1／3所支配区域建立心肌梗死模型

目的探讨大鼠左冠状动脉前降支中上1／3所支配的区域液氮冷冻处理后对心肌形态学及心功能的影响,以建立适合移植干细胞再生修复心肌梗死研究的一种新的大鼠心肌梗死模型制作方法。方法80只雄性SD大鼠,随机分为3组即：冷冻组、结扎组、对照组。大鼠麻醉后,行气管插管连通动物呼吸机,打开胸廓暴露心脏,用特制的直径为0．6cm冷冻头置入液氮中冷冻降温后迅速冷冻大鼠左冠状动脉前降支中上1／3所支配的区域,或结扎左冠状动脉前降支中上1／3处。分别于处理后1d、3d、7d、14d、28d观察心脏病理组织学变化,并于处理28d后检测心功能的变化。结果在液氮冷冻大鼠心脏后,大鼠心肌组织出现凝固性坏死,继而有肉芽组织长人梗死灶内,最后形成疤痕。用液氮冷冻法可成功复制心肌梗死大鼠动物模型。与冠状动脉结扎法相比较,操作简单,手术时间短,死亡率低．心肌梗死面积变异小。结论液氮冷冻法作为一种复制心肌梗死模型的方法,有其自身的优势．可用于心肌梗死发生机制和干细胞治疗等方面的研究。     

SD大鼠与Wistar大鼠脑胶质瘤动物模型的建立及比较

目的比较利用SD大鼠、Wistar大鼠建立脑胶质瘤动物模型的不同,为研究脑胶质瘤的发病机制及治疗方法提供操作平台。方法利用立体定向仪建立SD大鼠、Wistar大鼠大脑皮层接种C6细胞（2.5×105个细胞/只）,建立脑胶质瘤动物模型,利用组织病理学、免疫组织化学以及核磁共振成像等技术,比较两种动物模型在成瘤率、肿瘤生长状况、死亡率以及动物一般情况等方面的异同。结果SD大鼠组、Wistar大鼠组的成瘤率均为100%,两组均未见转移;但SD大鼠组肿瘤成瘤时间较长,且部分肿瘤有自愈倾向,而Wistar大鼠组则未出现类似情况。结论Wistar大鼠大脑皮层脑胶质瘤动物模型的肿瘤性状更接近于人的脑胶质瘤,因此更适合探索和研究脑胶质瘤的发病机制和治疗方法;而SD大鼠的肿瘤由于性状类似转移瘤,且有自愈倾向,不适合作为上述相关研究的动物模型。     

大鼠慢性心肌梗死模型制备的改进

目的 改进制备大鼠心肌梗死模型的方法,提高术后大鼠存活率.方法 采用戊巴比妥钠腹腔注射麻醉,开胸行冠状动脉前降支结扎法,术后给予呼吸道管理.结果 术后存活率达到76%,4周存活率达到67.5%.结论 准确结扎前降支才能保证造模成功,加强呼吸道管理是提高术后大鼠存活率的重要措施.     

MIJ和HFJ近交系大鼠心电图表现

目的 测定近交系MIJ、HFJ大鼠心电图,并与Wistar大鼠比较分析,观察MIJ和HFJ大鼠心电图表现.方法 大鼠麻醉后,仰卧位固定于大鼠固定板上,用短针电极刺入皮下2～3 mm位置,麻醉5 min后,用福田青岛FX-102B心电图机做心电图,并对心电图进行分析.结果 三种大鼠均为窦性心律,心律齐整,雄性HFJ、MIJ心率均高于同性别Wistar.HFJ和MIJ品系、性别间心率差异均无显著性.HFJ和MIJ心电轴与Wistar相同,主要在0°～90°间.三种大鼠的P波方向及QRS波群基本相同,但各波振幅和各波时限,在不同品系和性别之间存在较明显的差异.结论 近交系MIJ和HFJ大鼠各有其独特的心电图表现.     

子宫内膜异位症大鼠模型的建立及其病理学改变

目的构建子宫内膜异位症（内异症）大鼠动物模型,为阐明内异位症发病机理以及寻找有效的治疗方法提供理想的动物模型。方法取性成熟雌性Sprague-Dawley（SD）大鼠30只,通过手术将大鼠自体子宫组织移植到子宫旁韧带上,建立诱发型内异症大鼠动物模型。术后8周,再次剖腹观察异位组织的存活情况、病灶大小、与周围组织的粘连程度以及病理学变化。结果25只大鼠有明显的异位病灶。所有病灶都与周围组织有不同程度的粘连,病灶外观呈囊泡状。光镜观察见大部分异位子宫内膜形态和结构与在位子宫内膜基本相同,但内膜细胞、间质细胞、腺体,与在位内膜相比较少。少数病灶只有上皮组织或只有问质组织。结论自体子宫移植法可成功建立内异症大鼠模型。     

Differential cytokine expression in myocytes and non-myocytes after myocardial infarction in rats

The proinflammatory cytokines interleukin (IL)-1 and IL-6 are increased after acute myocardial infarction (MI). Moreover, serum IL-6 level is elevated after MI, but has also been associated with heart failure. In the present study, heart function was monitored in a rat model of chronic MI. Cytokine expression in the infarcted and non-infarcted myocardium as well as in hearts of sham-operated controls was measured by the ribonuclease-protection assay. To identify the cells contributing to the increased cytokine expression, we further analyzed myocytes and non-myocytes isolated in the acute phase as well as during congestive heart failure (CHF) after MI. There was a strong induction in cytokine expression in the myocytes of the infarct area 6 h after MI. In the non-infarcted myocardium, cytokine expression increased only slightly in the non-myocytes after 6 h. This was not different from sham-operated controls and may, therefore, be induced by stress and catecholamines. In CHF, however, cytokine expression level in myocytes was normal. It increased slightly but significantly in the non-myocytes 4 and 8 weeks after MI. In conclusion, we suggest that pro-inflammatory cytokines, produced by the ischemic myocytes may be involved in the initiation of wound healing of the necrotic area, whereas the effect of pro-inflammatory cytokines in CHF, if any, seems not to be crucial.     

Curcumin ameliorated myocardial infarction by inhibition of cardiotoxicity in the rat model

Cardiovascular diseases are the main cause of death globally. Many attempts have been done to ameliorate the pathological changes after the occurrence of myocardial infarction. Curcumin is touted as a polyphenol phytocompound with appropriate cardioprotective properties. In this study, the therapeutic effect of curcumin was investigated on acute myocardial infarction in the model of rats. Rats were classified into four groups; control, isoproterenol hydrochloride (ISO) (100 mg/kbw), curcumin (50 mg/kbw), and curcumin plus ISO treatment groups. After 9-day administration of curcumin, levels of lactate dehydrogenase (LDH), creatine kinase (CK), and cardiac troponin I (cTnI) were determined. Superoxide dismutase (SOD) and malondialdehyde (MDA) contents were measured to investigate the oxidative status in infarct rats received curcumin. By using H & E staining, tissue inflammation was performed. Masson’s trichrome staining was conducted to show cardiac remodeling and collagen deposition. The number of apoptotic cells was determined by using the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Data showed the serum decrease of LDH, CK, and cTnI in infarct rats after curcumin intake compared to the rats given (ISO) ( P < 0.05). Curcumin was found to reduce oxidative status by reducing SOD and MDA contents ( P < 0.05). Gross and microscopic examinations revealed that the decrease of infarct area, inflammation response and collagen deposition in rats given ISO plus curcumin ( P < 0.05). We noted the superior effect of curcumin to reduce the number of apoptotic cardiomyocytes after 9 days. Data point the cardioprotective effect of curcumin to diminish the complication of infarction by the reduction of cell necrosis and apoptosis in a rat model of experimental infarction.     

Effect of propranolol on cardiac cytokine expression after myocardial infarction in rats

The pro-inflammatory cytokines interleukin (IL)-1 and IL-6 have been shown to be upregulated in the myocardium after injury and after adrenergic receptor stimulation. Together with other cytokines, such as the transforming growth factor (TGF)-, the pro-inflammatory cytokines have been implicated in the initiation of tissue repair and wound healing after myocardial infarction (MI). In the present study, the effect of -adrenergic receptor blockade with propranolol (2 mg/kg·h s.c. by miniosmotic pumps) on cardiac cytokine expression and on wound healing was analyzed in rats from 6–72 h after MI. IL-1 and IL-6 gene expression strongly increased in the infarcted myocardium 6 h after MI and peaked after 12 h, while TGF-, progressively increased from 12 h onwards. Also, TGF-₂ increased after 12 h, peaked after 24 h and declined thereafter, while TGF-, was only elevated after 72 h. Treatment with propranolol had a negative chronotropic effect throughout the observation period of 72 h. It attenuated the initial elevation in LVEDP and increased cardiac output ultimately. Furthermore, propranolol attenuated IL-1 mRNA expression, but had not effect on the other cytokines. Moreover, MMP-9 gelatinolytic activity was markedly attenuated by propranolol indicating a delayed resorption of the necrotic tissue and, possibly, collagen turnover. Replacement by scar tissue, however, was not affected as indicated by normal collagen expression.     

Losartan inhibits myosin isoform shift after myocardial infarction in rats

Hypertrophy and heart failure following a myocardial infarction in rodents are accompanied by a switch of myosin isoforms from V₁ to V₃. The angiotensin II receptor blocker, Losartan, has been demonstrated to improve cardiac function and long-term survival after myocardial infarction. In this study we have investigated whether chronic Losartan treatment affects myosin isoform composition in the hearts of rats following a myocardial infarction. Rats were subjected to coronary artery ligation and received either Losartan (1 g/L) in the drinking water or water only. Four months after myocardial infarction, rats were classified as having either congestive heart failure (cMI) or uncomplicated myocardial infarction (uMI) based on their lung weight to body weight ratio (LW/BW). Compared with sham operated rats, uMI rats showed a 68.5% increase in the relative contribution of V₃ and a 33.7% decrease in the relative contribution of V₁ (p < 0.05). Untreated cMI showed 39.7% more V₃ and 38.2% less V₁ when compared with untreated uMI (p < 0.05). Losartan treatment after myocardial infarction reduced the incidence of cMI from 30.4 to 4.5% and scar size from 1.52 ± 0.07 to 0.94 ± 0.11 cm² respectively. The percentage of V₁ in Losartan treated uMI (LuMI) was 25.2% higher than the percentage of V₁ in untreated uMI (p < 0.05), whereas the percentage of V₃ in LuMI was 24.2% lower than that in untreated uMI (p < 0.05). A positive correlation of V₃ myosin and scar area was observed. Our study suggests that expression of V₃ myosin in the left ventricle is associated with scar size and the progress of hemodynamic changes after myocardial infarction. Losartan treatment reduces scar size and wall stress of the heart after the infarct, and therefore inhibits the signals shifting myosin isoform expression from V₁ to V₃ after a myocardial infarction.     

Overexpression of sema3a in myocardial infarction border zone decreases vulnerability of ventricular tachycardia post‐myocardial infarction in rats

The expression of the chemorepellent Sema3a is inversely related to sympathetic innervation. We investigated whether overexpression of Sema3a in the myocardial infarction (MI) border zone could attenuate sympathetic hyper‐innervation and decrease the vulnerability to malignant ventricular tachyarrhythmia (VT) in rats. Survived MI rats were randomized to phosphate buffered saline (PBS, n = 12); mock lentivirus (MLV, n = 13) and lentivirus‐mediated overexpression of Sema3a (SLV, n = 13) groups. Sham‐operated rats served as control group (CON, n = 20). Cardiac function and electrophysiological study (PES) were performed at 1 week later. Blood and tissue samples were collected for histological analysis, epinephrine (EPI), growth‐associated factor 43 (GAP43) and tyrosine hydroxylase (TH) measurements. QTc intervals were significantly shorter in SLV group than in PBS and MLV groups (168.6 ± 7.8 vs. 178.1 ± 9.5 and 180.9 ± 8.2 ms, all P < 0.01). Inducibility of VT by PES was significantly lower in the SLV group [30.8% (4/13)] than in PBS [66.7% (8/12)] and MLV [61.5% (8/13)] groups (P < 0.05). mRNA and protein expressions of Sema3a were significantly higher and the protein expression of GAP43 and TH was significantly lower at 7 days after transduction in SLV group compared with PBS, MLV and CON groups. Myocardial EPI in the border zone was also significantly lower in SLV group than in PBS and MLV group (8.73 ± 1.30 vs. 11.94 ± 1.71 and 12.24 ± 1.54 μg/g protein, P < 0.001). Overexpression of Sema3a in MI border zone could reduce the inducibility of ventricular arrhythmias by reducing sympathetic hyper‐reinnervation after infarction.     

Berbamine ameliorates isoproterenol-induced myocardial infarction by inhibiting mitochondrial dysfunction and apoptosis in rats

Berbamine (BBM), a bisbenzylisoquinoline alkaloid from roots, bark, and stem of Berberis plant such as Berberis aristata has a wide range of pharmacological activities. However, the evidence for the cardioprotective effect of BBM is inadequate and the molecular mechanism of BBM remains unclear. This study investigated the underlying molecular mechanism of BBM-mediated cardioprotection on isoproterenol (ISO)-induced mitochondrial dysfunction and apoptosis in rats. The assays of mitochondria antioxidant status, mitochondrial marker enzymes, and electron microscopic analysis of mitochondria revealed BBM significantly prevented the mitochondrial dysfunction induced by ISO. The ISO-induced elevation of mitochondrial oxidative stress was also curbed by BBM. Furthermore, pretreatment with BBM protected the heart tissue from ISO-induced apoptosis as evident from decreased terminal dUTP nickend-labeling positive cells and decreased expression of Bax, cytochrome c, cleaved caspase-9, and caspase-3, and poly (ADP-ribose) polymerase and increased expression of Bcl-2 in ISO-induced rats. These current findings suggest that BBM exerts a significant cardioprotective effect on ISO-induced myocardial infarction in rats.     

Mesenchymal stem cells are superior to angiogenic growth factor genes for improving myocardial performance in the mouse model of acute myocardial infarction

Summary Both cell therapy and angiogenic growth factor gene therapy have been applied to animal studies and clinical trials. Little is known about the direct comparison between cell therapy and angiogenic growth factor gene therapy. The goal of this study was to compare the effects of human bone marrow-derived mesenchymal stem cells (hMSCs) transplantation and injection of angiogenic growth factor genes in a model of acute myocardial infarction in mice. The hMSCs were obtained from adult human bone marrow and expanded in vitro. The purity and characteristics of hMSCs were identified by flow cytometry and immunophenotyping. Immediately after ligation of the left anterior descending coronary artery in male severe combined immunodeficient (SCID) mice, culture-expanded hMSCs or angiogenic growth factor genes were injected intramuscularly at the left anterior free wall. The engrafted hMSCs were positive for cardiac marker, desmin. Infarct size was significantly smaller in the hMSCs-treated group than in the angiopoietin-1 (Ang-1) or vascular endothelial growth factor (VEGF)-treated group at day 28 after infarction. hMSCs transplantation was better in decreasing left ventricular end-diastolic dimension and increasing fractional shortening than Ang1 or VEGF gene therapy. Capillary density was markedly increased after hMSCs transplantation than Ang1 and VEGF gene therapy. In conclusion, intramyocardial transplantation of hMSCs improves cardiac function after acute myocardial infarction through enhancement of angiogenesis and myogenesis in the ischemic myocardium. hMSCs are superior to angiogenic growth factor genes for improving myocardial performance in the mouse model of acute myocardial infarction. Transplantation of MSCs may become the future therapy for acute myocardial infarction for myocardial regeneration.     

Diagnostic value of the electrocardiogram in the assessment of prior myocardial infarction

BackgroundThe best available imaging technique for the detection of prior myocardial infarction (MI) is cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE). Although the electrocardiogram (ECG) still plays a major role in the diagnosis of prior MI, the diagnostic value of the ECG remains uncertain. This study evaluates the diagnostic value of the ECG in the assessment of prior MI.MethodsIn this retrospective study, data from electronic patient files were collected of 1033 patients who had undergone CMR with LGE between January 2014 and December 2017. After the exclusion of 59 patients, the data of 974 patients were analysed. Twelve-lead ECGs were blinded and evaluated for signs of prior MI by two cardiologists separately. Disagreement in interpretation was resolved by the judgement of a third cardiologist. Outcomes of CMR with LGE were used as the gold standard.ResultsThe sensitivity of the ECG in the detection of MI was 38.0% with a 95% confidence interval (CI) of 31.6–44.8%. The specificity was 86.9% (95% CI 84.4–89.1%). The positive and negative predictive value were 43.6% (95% CI 36.4–50.9%) and 84.0% (95% CI 81.4–86.5%) respectively. In 170 ECGs (17.5%), the two cardiologists disagreed on the presence or absence of MI. Inter-rater variability was moderate (κ 0.51, 95% CI 0.45–0.58, p < 0.001).ConclusionThe ECG has a low diagnostic value in the detection of prior MI. However, if the ECG shows no signs of prior MI, the absence of MI is likely. This study confirms that a history of MI should not be based solely on an ECG.     

改良气管插管法在小鼠心肌梗死模型制备中的应用

目的：小鼠心肌梗死模型制备中采用改良气管插管方法,提高模型制备成功率。方法：小切口暴露小鼠气管,直视下进行经口气管插管,左冠状动脉前降支结扎制备心肌梗死模型,观察、记录小鼠心脏颜色和心电图、术后14d存活情况和心肌组织病理学变化。结果：采用改良气管插管,成功完成40只小鼠心肌梗死模型制作,均可见冠状动脉结扎后,心室前壁颜色变暗,心电图Ⅱ导联ST段明显抬高。除去手术过程中意外死亡,术后14d存活27只,心肌梗死小鼠实际成活率达到87．1％。开胸后,肉眼可见模型组小鼠左室心腔明显扩大,心室壁变薄;病理切片HE染色,镜下可见心肌纤维断裂溶解,心肌细胞坏死,大量炎性细胞浸润。结论：在小鼠心肌梗死模型制备中,采用改良气管插管法,操作简单、易行、创伤小,模型制备成功率高。     

Intramyocardial transplantation of cardiac telocytes decreases myocardial infarction and improves post‐infarcted cardiac function in rats

The midterm effects of cardiac telocytes (CTs) transplantation on myocardial infarction (MI) and the cellular mechanisms involved in the beneficial effects of CTs transplantation are not understood. In the present study, we have revealed that transplantation of CTs was able to significantly decrease the infarct size and improved cardiac function 14 weeks after MI. It has established that CT transplantation exerted a protective effect on the myocardium and this was maintained for at least 14 weeks. The cellular mechanism behind this beneficial effect on MI was partially attributed to increased cardiac angiogenesis, improved reconstruction of the CT network and decreased myocardial fibrosis. These combined effects decreased the infarct size, improved the reconstruction of the LV and enhanced myocardial function in MI. Our findings suggest that CTs could be considered as a potential cell source for therapeutic use to improve cardiac repair and function following MI, used either alone or in tandem with stem cells.