混合高脂饲料喂养新西兰白兔建立DHF模型的实验

目的 使用无创方法建立兔舒张性心力衰竭模型.方法 采用混合高脂饲料喂养新西兰白兔12周,并设正常饲料组进行对照观察.结果 模型组与空白对照组比较,心室内压(LVSP)、收缩指数、左心室收缩期最大压力上升下降速率(LV±dp/dtmax)差异有统计学意义(P<0.05或P<0.01),符合舒张性心力衰竭动物模型.结论 采用混合高脂饲料喂养新西兰白兔可以建立动物舒张性心力衰竭的模型.     

高脂高糖饮食诱导胰岛素抵抗大鼠心脏功能和心肌Ⅰ型胶原改变及替米沙坦干预的影响

目的 探讨高脂高糖饮食诱导胰岛素抵抗大鼠心脏功能和心肌Ⅰ型胶原改变及替米沙坦干预后对其影响。方法 27只Wistar大鼠随机分为正常对照组(n=9只)、高脂高糖饮食组（n=18只）,高脂高糖饮食干预12周后确定胰岛素抵抗模型建立,将高脂高糖饮食组随机分为高脂高糖组（n=9只）和替米沙坦组（n=9只）。饮食干预34周后颈动脉插管测左室舒张末内压（LVEDP）、左室收缩压（LVSP）和左室内压最大下降速率（-dP/dtmax）。ELISA方法检测血浆中心肌Ⅰ型胶原代谢标志物Ⅰ型前胶原末端的前肽序列(PICP)和Ⅰ型胶原吡啶交联终肽(ICTP)的含量。心肌组织Masson染色进行心肌间质胶原定量分析。结果 与正常对照组比较,高脂高糖组大鼠LVEDP上升,-dP/dtmax下降(P<0.01),血浆PICP含量及PICP/ICTP升高(P<0.01),左室心肌胶原容积分数增高(P<0.01)。与高脂高糖组大鼠比较,替米沙坦组大鼠LVSP、LVEDP均显著下降(P<0.01),-dP/dtmax升高(P<0.05);血浆PICP含量、PICP/ICTP降低(P<0.05)。左室心肌胶原容积分数含量显著下降(P<0.01)。左室心肌组织胶原含量与胰岛素抵抗指数呈显著正相关(R=0.634,P<0.01),与-dp/dtmax呈显著负相关(P<0.01)。结论 胰岛素抵抗大鼠心肌Ⅰ型胶原合成增加,心肌间质胶原沉积增加,心脏舒张功能下降;替米沙坦可改善胰岛素抵抗,减少胰岛素抵抗大鼠心肌Ⅰ型胶原的合成,减少心肌间质胶原沉积,改善心脏舒张功能。     

基于Notch通路研究蓟黄素对心肌缺血再灌注大鼠的心肌保护作用

目的 探讨蓟黄素对心肌缺血再灌注大鼠Notch信号通路及心肌保护的作用。方法 50只Wistar大鼠随机分为假手术组、心肌缺血再灌注大鼠模型组、蓟黄素组（灌胃100 mg/kg蓟黄素）、抑制剂组、蓟黄素+抑制剂组，每组10只。测定大鼠心律失常发生率、持续时间及大鼠左心室舒张末期压力（left ventricular end-diastolic pressure,LVEDP）、左心室收缩压（left ventricular systolic pressure,LVSP）、左心室内压力下降最大速率（left ventricular pressure drop,LV-dp/dtmax）、左心室内压力上升最大速率（left ventricular pressure rise,LV+dp/dtmax）；染色法测定大鼠心肌梗死百分比；酶联免疫吸附测定（ELISA）法测定大鼠血清白细胞介素（interleukin,IL）-6、IL-10、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)及心肌组织中丙二醛（malondialdehyde,MDA）、超氧化物歧化酶（supe...     

血管内皮生长因子在异丙肾上腺素诱导大鼠心力衰竭中的变化及卡维地洛干预的影响研究

目的探讨异丙肾上腺素（isoproterenol,ISO）诱导心力衰竭大鼠血浆血管内皮生长因子（Vascularendothelial growth factor,VEGF）的变化及卡维地洛对VEGF的影响。方法将36只雄性SD大鼠随机分为3组：（1）ISO组（n=13）：给予致心力衰竭剂量的ISO腹腔注射10d后以0.9%氯化钠溶液灌胃4周;（2）：卡维地洛组（n=13）：给予ISO 10d后再以卡维地洛灌胃4周;（3）：对照组（n=10）：均以0.9%氯化钠溶液先腹腔注射10d再灌胃4周。40d后,随机从各组中选取存活的8只,测定各组大鼠血流动力学指标及左室肥厚指数,在实验前后分别测定血浆VEGF浓度。结果 ISO组与对照组相比,左室舒张末压（LVEDP）明显增高,而左室收缩压（LVSP）、左室压力最大上升速率（dp/dtmax）、左室压力最大下降速率（dp/dtmin）明显降低。左室重量、左室肥厚指数明显增加,血浆VEGF明显增加（P均〈0.01）。卡维地洛组与ISO组相比,LVEDP明显降低,dp/dtmax、dp/dtmin升高,左室重量降低,左室肥厚指数明显下降,VEGF明显降低,差异均有统计学意义。结论 ISO致心力衰竭大鼠血浆VEGF水平明显升高,与心功能相关。卡维地洛能够改善心功能并逆转心力衰竭时VEGF的升高。表明VEGF参与心力衰竭的发生发展,卡维地洛可能通过对VEGF的作用影响心力衰竭进程。     

辛伐他汀联合辅酶Q10对慢性心力衰竭大鼠心肌结缔组织生长因子表达的影响

目的探讨辛伐他汀联合辅酶Q10对慢性心力衰竭大鼠结缔组织生长因子(CTGF)表达的影响。方法利用腹主动脉缩窄法制作雄性SD大鼠慢性心力衰竭模型,随机分为模型组、辛伐他汀组、辅酶Q10组、联合用药组,另设假手术组,每组8只大鼠,观察各组大鼠血流动力学参数(左室舒张末压,左室内压上升、下降最大速率)和左心室心肌组织病理学改变,免疫组化检测各组大鼠左心室心肌中CTGF表达情况。结果与模型组相比,辛伐他汀组、辅酶Q10组和联合用药组左室舒张末压显著降低(P<0.01),最大收缩、舒张速率显著升高(P<0.01),左心室心肌CTGF阳性表达水平显著降低;联合用药组较辛伐他汀组、辅酶Q10组改变更为显著(P<0.01或P<0.05)。结论辛伐他汀与辅酶Q10联合应用较两药单独应用改善心力衰竭大鼠心功能、抑制心室重塑和减少CTGF表达作用明显。     

降糖舒心方混悬液灌胃对大鼠糖尿病心力衰竭的治疗作用及其机制

目的 观察降糖舒心方灌胃对大鼠糖尿病心力衰竭（DHF）的治疗作用，并探讨其机制。方法 将50只SD大鼠随机分为5组各10只，低剂量组、高剂量组、西药组、模型组制备DHF模型，对照组不制备DHF模型。低剂量组灌胃给予1.0 g/（kg·d）的降糖舒心方混悬液，高剂量组灌胃给予1.5 g/（kg·d）的降糖舒心方混悬液，西药组灌胃给予格列喹酮和贝那普利，均连续灌胃2个月，高脂饲料喂养；对照组给予普通饲料喂养。比较各组大鼠空腹血糖（FBG）及血清甘油三脂（TG）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）、C反应蛋白（CRP）、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、肌酸激酶同工酶（CK-MB）、乳酸脱氢酶（LDH）和心肌组织病理形态、NF-κB p65蛋白、IκBα蛋白。结果 与对照组比较，其余4组大鼠FBG及血清TG、LDL-C、CRP、IL-6、TNF-α、CK-MB、LDH水平升高，血清HDL-C水平下降，心肌组织损伤严重，NF-κB p65蛋白表达升高，IκBα蛋白表达下降（P均<0.05）。与模型组比较，低剂量组、高剂量组、西药组...     

舒张功能不全超声心动图分级和左室充盈压的评价

在心力衰竭患者中，单纯性舒张性心力衰竭（DHF）约占30％～50％，高龄和女性患者则更高。DHF主要是由于左室舒张功能不全（DD）引起左室充盈压的增高最终导致心力衰竭，故正确认识DD并定量评价左室充盈压对DHF的治疗和预后都至关重要。本文就从DD的定义、超声心动图分级及左室充盈压的评价等方面进行综述。     

骨髓干细胞移植对AMI后左室重构及心功能影响的实验研究

将雄性Wistar大鼠50只随机分为移植组及对照1、2、3组。用结扎冠状动脉左前降支的方法建立大鼠急性心肌梗死（AMI）模型。对照1组单纯开胸但不结扎冠状动脉；对照2组仅建立AMI模型；对照3组将培养基经心外膜下植入梗死心肌周围；移植组将制备好的同种异体骨髓单个核细胞（BM-MNCs）悬液经心外膜下植入梗死心肌周围。移植术后4周末，超声心动图及心导管检查评价左室形态及功能，并观察梗死区及其周边区心肌内移植BM-MNCs组织形态学特点。结果与对照1组相比，对照2、3组及移植组左室收缩末期内径（LVEDs）、左室舒张末期内径（LVEDd）和左室舒张末压（LVEDP）均显著升高（P〈均0．05），左室射血分数（LVEF）、左室短轴缩短率（LVFS）、左室收缩压（LVSP）、左室压最大上升速率（＋dp／dtmax）和左室压最大下降速率（-dp／dtmax）均显著降低（P均〈0．05）；移植组LVEDs、LVEDd和LVEDP显著低于对照2、3组（P均〈0．05），LVEF、LVFS、＋dp／dmax。和-dp／dtmax显著高于对照2、3组（P均〈0．05）；免疫组织化学检查发现移植组AMI区内有存活的BrdU标记阳性的BM-MNCs。证实同种异体大鼠BM-MNCs移植可减轻急性AMI后的左心室扩大，抑制左室重构，改善AMI后的心脏功能。     

天麻舒心方对SHR左心室舒张功能损伤的保护研究

目的探讨天麻舒心方对自发性高血压大鼠(SHR)降压及左心室舒张功能损伤的保护作用。方法 50只SHR大鼠随机分为天麻舒心方高、中、低剂量组及阳性药对照组、模型组,并以10只Wistar大鼠作为正常对照。分别给予不同剂量天麻舒心浸膏、氯沙坦片混悬液、蒸馏水。每2周测量血压心率;18周后应用心导管术观测左室舒张末压(LVEDP)、左室压力最大下降速度(-dp/dtmax)。结果给药后,各治疗组血压均显著低于模型组(P0.01),心率无统计学意义。模型组LVEDP显著上升(P0.01),-dp/dtmax绝对值显著下降(P0.01),与之相比,西药组与中药各剂量组的LVEDP下降,-dp/dtmax绝对值上升,具有统计学意义(P0.05或P0.01)。结论 SHR左心室舒张功能损伤以LVEDP上升,-dp/dtmax绝对值下降为特点,天麻舒心方有效降压,同时对SHR左室舒张功能损伤具有保护作用。     

家兔颈总动脉不稳定斑块模型的建立

目的 建立家兔颈总动脉斑块模型。方法 选取60只雄性纯种的新西兰大白兔,随机分为3组,即球囊损伤+高脂组、高脂喂养组及普通饲料喂养组,每组20只。喂养12周后,分别给予中国斑点蝰蛇毒和组胺药物触发,诱发斑块破裂及血栓形成。结果 球囊损伤+高脂组存活17只白兔中,有38处病变狭窄程度超过50％,并且脂质核心较大、纤维帽的厚度小于65 μm,故判定以上38处病变为易损斑块。高脂喂养组中的19只白兔仅8处可判定为易损斑块;普通饲料喂养组中未见易损斑块。结论 高脂饮食饲养后,进行颈总动脉球囊拉伤制作兔易损斑块模型是切实可行的方法。     

胸内负压增大对家兔实验性冠脉供血不足的治疗作用

本实验首先以22只家兔为对象用垂体后叶素制造心肌供血不足模型（模型组），待家兔完全恢复正常以后，再同样制造模型，同时增大胸内负压（低胸内压组）。发现低胸内压组心电图缺血性ST-T改变恢复，P-R间期缩短，心率增快（P＜0．05），心肌供血不足比模型组减轻。另外用垂体后叶素造成心功能降低后，增大胸内负压时，左室最大收缩压、左室压最大上升和下降速率均明显增大（P＜0．01），左室舒张末期压降低（P＜0.05）。心功能的增强是由于冠脉血流增加，心肌等长自身调节结果。本研究为临床上呼吸训练治疗心肌缺血提供了科学依据。     

温补心阳和肾阳方对心力衰竭大鼠心功能和心肌磷酸腺苷含量的影响

目的研究温补心阳和肾阳方对心力衰竭大鼠心功能和心肌磷酸腺苷含量的影响。方法采用结扎冠状动脉前降支术制备心力衰竭大鼠模型,用温补心阳和温补肾阳方于术后2周灌胃,以假手术组为空白对照组,曲美他嗪为阳性药物对照组。给药8周,采用酶联免疫吸附法检测心梗后心力衰竭大鼠药物干预前后脑钠肽(BNP)水平,测定治疗后血流动力学改变,包括心率(HR)、左室收缩压(LVSP)、左室舒张压(LVEDP)、左室内压上升下降最大速率(±LVdp/dtmax),并行高效液相法测定心肌组织中AMP、ADP、ATP的含量。结果对心力衰竭大鼠心功能的影响,温补心阳和肾阳组较模型组,显著降低BNP水平(P<0.01),改善心肌收缩、舒张功能。而肾阳组大鼠LVSP、+LVdp/dtmax较心阳组升高(P<0.05),LVEDP、-LVdp/dtmax、HR、BNP较心阳组降低(P<0.05)。对心力衰竭大鼠心肌磷酸腺苷含量的影响:温补心阳和肾阳组大鼠较模型组心肌AMP、ADP降低(P<0.05),ATP含量升高,而肾阳组大鼠心肌ATP含量显著高于模型组(P<0.01),较心阳组更接近曲美他嗪和假手术组。结论温补心阳和温补肾阳可改善心力衰竭大鼠能量代谢,提高心功能,其中以温补肾阳作用更显著。     

携ICAM-1靶向超声造影评估动脉粥样硬化兔心肌微循环的实验研究

目的应用携细胞间黏附分子-1(ICAM-1)靶向超声造影评估动脉粥样硬化兔心肌血流灌注。方法将16只雄性新西兰大白兔随机分为对照组和动脉硬化组,各8只。动脉硬化组高脂喂养12周后建立动脉粥样硬化模型,两组实验兔均行常规超声心动图和携ICAM-1靶向心肌超声造影检查,评估心肌血流灌注,同时取心肌组织进行病理学测定。结果两组室间隔舒张期厚度(IVS)和左室后壁舒张期厚度(LVPW)、左室舒张末期内径(LVEDD)、左室收缩末期内径(LVESD)及左室射血分数(LVEF)比较,差异均无统计学意义(P>0.05)。心肌声学造影显示:两组实验兔心肌血流灌注呈均匀一致性,动脉硬化组心肌灌注峰值强度低于对照组,心肌灌注达峰时间晚于对照组(P<0.01)。结论携ICAM-1靶向造影剂心肌造影检查可敏感评估动脉粥样硬化兔早期心肌微循环障碍,可作为动脉粥样硬化性心脏病早期诊断和动态疗效监测的有效方法。     

Acute haemodynamic effect of taurine on hearts in vivo with normal and depressed myocardial function

The acute haemodynamic effects of taurine were studied in normal and in beta blocker (propranolol) or calcium antagonist (diltiazem) treated rabbits and in rabbits with experimentally produced chronic aortic regurgitation. The administration of taurine (25 mg.kg-1) did not affect heart rate and left ventricular end diastolic pressure but produced significant increases in left ventricular dP/dtmax, cardiac output, and left ventricular systolic pressure in control hearts, indicating that intravascularly administered taurine substantially increased cardiac performance. In propranolol (1 mg.kg-1) treated rabbits taurine significantly improved left ventricular dP/dtmax and cardiac output, which were previously depressed by propranolol. Taurine had the same effect on diltiazem (1 mg.kg-1) treated rabbits. In rabbits with aortic regurgitation a bolus injection of taurine improved cardiac performance. Continuous infusion of taurine (100 mg.h-1) also produced a significant increase in left ventricular dP/dtmax. These results suggest that taurine has a unique action as an inotropic agent and that it may be useful in the treatment of patients with congestive heart failure.     

Development of different phenotypes of hypertensive heart failure: systolic versus diastolic failure in Dahl salt-sensitive rats

OBJECTIVE: There are two phenotypes of heart failure, systolic failure and isolated diastolic heart failure with preserved left ventricular systolic function. Although isolated diastolic heart failure frequently occurs, there are only models for diastolic dysfunction unassociated with heart failure and models with overt diastolic heart failure have not been established. We attempted to develop two different models, i.e. diastolic and systolic failure models, based on hypertension. MATERIALS AND METHODS: Dahl salt-sensitive rats were placed on 8% NaCl diet from 7 weeks old (7-week starting group) or 8 weeks old (8-week starting group). As an age-matched control, Dahl salt-sensitive rats were consistently placed on normal chow. In these rats, echocardiogram was serially recorded, followed by hemodynamic and histological studies. RESULTS: The 7-week starting rats showed a steep elevation in blood pressure and progressive left ventricular hypertrophy, and fell into overt heart failure at approximately 19 weeks. The development of heart failure was not associated with a decrease in left ventricular midwall fractional shortening or an increase in left ventricular end-diastolic dimension as compared with the age-matched control, which mimics the characteristics of clinically observed isolated diastolic heart failure. The 8-week starting rats showed a gradual rise in blood pressure and less progressive left ventricular hypertrophy, and fell into heart failure at approximately 26 weeks with a decrease in mid-wall fractional shortening and an increase in left ventricular end-diastolic dimension. Hemodynamic and histological studies at failing stage revealed comparable elevation of left ventricular end-diastolic pressure and comparable left ventricular fibrosis in both groups. CONCLUSION: These two different models of overt heart failure may be useful as models of isolated diastolic heart failure and systolic heart failure based on the same hypertensive heart disease, respectively, and may contribute to discrimination of the mechanisms of the development of the two different phenotypes of heart failure.     

A diet high in saturated fat and sucrose alters glucoregulation and induces aortic fatty streaks in New Zealand White rabbits

A new and convenient animal model for studying peripheral vascular and coronary artery disease in diabetes was established in this study. Male New Zealand White rabbits weighing approximately 2 kg were divided into 2 groups: a normal control group fed standard laboratory chow and a diabetogenic diet-fed group received a high-fat/high-sucrose diet. The high-fat/high-sucrose diet (contained 10% lard and 37% sucrose) feeding was maintained for 6 months. Plasma total cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride, superoxide dismutase, nitric oxide, nitric oxide synthase, insulin, and glucose were quantitated at monthly or bimonthly intervals. The aortic fatty streak lesions were quantified following lipid staining with Sudan IV. The aortic samples were observed by electron microscopy. High plasma triglyceride and glucose concentrations were induced. At the end of 6 months, the aortic fatty streak lesions were present in the animals' vascular specimens. As far as we know, this is the first report that demonstrates that New Zealand White rabbits can develop obvious aortic fatty streaks by feeding a high-fat/high-sucrose diet. Our results suggest that New Zealand White rabbits fed a high-fat/high-sucrose diet would provide a convenient model for studying peripheral vascular-and coronary artery disease in diabetes.     

Diastolic compliance is reduced in obese rabbits

Obesity often leads to symptoms of cardiopulmonary congestion associated with normal systolic but abnormal diastolic function. This study analyzed alterations in passive diastolic compliance in obesity using the rabbit model. New Zealand White rabbits were fed a normal (n=8) or 10% added fat diet (n=8). After 12 weeks, rabbits fed the high fat diet developed obesity (5.34+/-0.11 versus 3.68+/-0. 04 kg, P相似文献   

Amplitude and velocity of mitral annulus motion in rabbits

OBJECTIVE: During recent years, the amplitude and the maximal systolic velocity of the mitral annulus motion (MAM) have been established as indices of the left ventricular systolic function and the maximal diastolic velocity of the annulus motion has been suggested as an index of diastolic function. The main aims of the present study were to investigate the feasibility of these techniques in rabbits and to investigate age-related changes concerning these variables. METHODS: Twenty-one New Zealand white rabbits were investigated by echocardiographic M-mode and pulsed tissue Doppler. One subgroup (I) included 11 still-growing, 3.0 +/- 0.2 month-old, animals and another group (II) included 10 young grown up rabbits, 12.1 +/- 1.5 months old. RESULTS: The amplitude (4.8 +/- 0.6 and 3.5 +/- 0.3 mm, respectively) and maximal systolic (98 +/- 14 and 66 +/- 7 mm/s, respectively) and diastolic (111 +/- 21 and 80 +/- 12 mm/s, respectively) velocities of the MAM were significantly (P < 0.001) higher in group I than in group II, despite a bigger heart in the animals in the latter group. A coefficient of variation of <5% was found for both inter- and intraobserver variability for both amplitude and velocities. CONCLUSIONS: The amplitude and velocities of MAM are easily recorded in rabbits with excellent reproducibility and the changes with age seem to be very similar to those in humans. These noninvasive M-mode and tissue Doppler methods are therefore suitable for the investigation of left ventricular function in experimental studies in rabbits.     

新西兰兔腹主动脉缩窄术后心肌收缩和舒张功能的变化

目的观察新西兰兔腹主动脉缩窄术后不同时间点心肌收缩和舒张功能的变化。方法30只新西兰兔随机分为2组:手术组(20只)行腹主动脉缩窄术,假手术组(10只)作为对照。术后观察兔精神状态、饮食、活动等变化。手术前后监测血流动力学变化并定期行超声心动图检查。结果术后4周,手术组出现心室肥厚,等容舒张时间延长。术后8周,组织多普勒提示二尖瓣舒张早期血流峰速与舒张晚期血流峰速比值和心肌收缩期血流峰速降低,左心室舒张末压升高(P<0.05);而射血分数无显著差异。结论腹主动脉缩窄术后可造成舒张功能的损伤,同时也伴有轻度收缩功能的损伤。     

辛伐他汀干预对慢性心力衰竭兔模型心室重构的影响

目的观察辛伐他汀对慢性心力衰竭兔心室重构的影响.方法将24只新西兰白兔分为4组,每组6只,第1、第2、第3组通过破坏主动脉瓣和缩窄腹主动脉,增加左心室前、后负荷,建立慢性心力衰竭模型.第1组:心力衰竭对照组;第2组:心力衰竭早干预组,术后每天给予辛伐他汀5 mg/kg灌胃,观察6周;第3组:心力衰竭晚干预组,手术4周后每天给予辛伐他汀5 mg/kg灌胃,观察4周;第4组为假手术组.各组术后及观察结束时行超声心动图检查;观察心肌细胞肥大情况;计算各组凋亡指数.结果早干预组室间隔厚度(LVSd)、左心室舒张期内径(LVIDd)、左心室后壁厚度(LVPwd)、左心室收缩期内径(LVIDs)、心脏重量、左心室重量、心脏/体重、左心室/体重、心肌细胞凋亡指数(AI)显著低于心力衰竭对照组;左心室射血分数(EF)、左心室长轴缩短率(FS)显著高于心力衰竭对照组.晚干预组LVSd、LVIDs、心脏重量、左心室重量、心脏/体重、心肌细胞凋亡指数(AI)显著低于心力衰竭对照组;EF、FS显著高于心力衰竭对照组.结论辛伐他汀干预可抑制慢性心力衰竭兔心脏扩张、室壁增厚、心肌细胞调亡,改善心肌重构.