冠脉结扎法制做大鼠心肌缺血模型

目的探讨大鼠心肌缺血动物模型的构建。方法缝扎大鼠冠脉左前降支,于左室前外侧壁形成缺血区域,约占左室壁面积的20%～50%。结果完成85例动物模型制作,存活74只,其中60只据术中所见、心电图、及病理检查证实有明确的心肌缺血,心功能下降。结论该方法制作简单可行,动物存活率满意;但模型欠稳定,需标本量较大以充分筛选。     

灯延颗粒对结扎冠状动脉所致大鼠心肌缺血的影响

目的:观察灯延颗粒对结扎冠状动脉所致大鼠心肌缺血的影响。方法:采用结扎冠状动脉左前降支致心肌缺血模型,灯延颗粒0.35、0.70、1.40g/kg灌胃给药14天后,观察灯延颗粒的药理作用。结果:①灯延颗粒对心肌缺血大鼠的心脏功能有明显的改善作用,能增强心肌收缩力,改善心肌舒张的顺应性,表现为心率加快、颈动脉血压、左心室内收缩压、左心室压力微分±dp/dt明显增高,与模型组比较有明显差异(P<0.05或P<0.01);②模型组与假手术组比较血清中SOD、LDH、CK含量显著升高,MDA显著降低;灯延颗粒能明显减少血清中SOD、LDH、CK含量,明显增加血清中MDA含量,与模型组比较有显著差异(P<0.05或P<0.01);③模型组大鼠出现明显的心肌缺血和心肌梗死;灯延颗粒各组心肌缺血及心肌梗死程度与模型组比较,其病变程度显著减轻(P<0.01);④光镜观察可见灯延颗粒能明显减轻心肌病理损伤。结论:灯延颗粒对大鼠结扎冠状动脉所致心肌缺血损伤具有明显的保护作用。     

Temporal Profile of Levels of Monoamines and Their Metabolites in Striata of Rats Implanted with Dialysis Tubes

We have measured the levels of monoamines and their metabolites in rat striata implanted with a dialysis tube, in contralateral nonimplanted striata, and in dialysates obtained from the dialysis tube. The perfusion was done with Ringer solution. The animals were perfused either for a continuous period of 7 h at 1 day after implantation or for periods of 2 h on days 1, 4, and 7 after implantation. In animals perfused for 7 h, levels of monoamine metabolites in dialysates remained stable for the first 4 h of perfusion, but a reduction was observed during the last 3 h. In animals perfused for 2 h on days 1, 4, and 7 after implantation, we observed a progressive reduction in levels of metabolites in dialysates with respect to the first day of perfusion. The levels of dopamine and its metabolites in the striata in which a dialysis cannula had been implanted showed a progressive reduction during the period postimplantation comparable to that observed in dialysates. The levels of 3-methoxytyramine, 3,4-dihydroxyphenylacetic acid, and homovanillic acid were elevated 24 h after implantation in the implanted striata with respect to the contralateral nonimplanted striata, but 7 days after implantation, the levels of dopamine were decreased in the implanted striata, and the levels of metabolites were unchanged.     

Wistar大鼠运动皮层代表区的微刺激测定

在１５例氯胺酮麻醉的Ｗｉｓｔａｒ大鼠利用皮层内微刺激技术测定了躯体的运动皮层代表区。电刺激为３５０Ｈｚ的阴极串脉冲,电流最大值限为８０μＡ。结果表明大多数皮层点诱发对侧肌肉反应。虽然代表区的大小有很大个体差异,分区的相对位置是恒定的。但在分区内部未见分域排列。部分大鼠存在前部前肢区,但无一例发现前部后肢区。比较文献结果提示Ｗｉｓｔａｒ大鼠的运动皮层的分化程度比Ｌｏｎｇ－Ｅｖａｎｓ黑顶鼠低。     

Regional and Temporal Changes in Proteomic Profile after Middle Cerebral Artery Occlusion with or without Reperfusion in Rats

Although DNA microarray studies showed up-regulation of various genes, failures of translation of many genes are expected to occur under ischemic conditions even in the penumbra with mild reduction in cerebral blood flow. We applied surface enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI-TOF-MS) technology to study proteomic profile at 6, 12, and 24 h after photothrombotic middle cerebral artery (MCA) occlusion with or without YAG laser-induced reperfusion in adult male spontaneously hypertensive rats. Of the 43 protein peaks that differed from the sham-operation group with a criterion (no overlap of peak intensities between the two groups), 36 peaks (84%) were down-regulated, and seven were up-regulated. All increased peaks showed greater than twofold increases (up to 8.1 fold) compared with those in the sham-operation group. Effects of reperfusion were observed mainly at 24 h after 1 h of MCA occlusion only in the penumbra, where 23 of 32 peaks returned toward the control values, whereas none of 33 peaks showed such attenuation in the ischemic core. Major ischemia-induced changes in protein peaks detected with SELDI-TOF-MS were down-regulations. The present study showed that dynamic changes of protein profile were associated with progression and recovery of the ischemic core and penumbra.     

Temporal Profile of Astrocytes and Changes of Oligodendrocyte-Based Myelin Following Middle Cerebral Artery Occlusion in Diabetic and Non-diabetic Rats

The long-term impacts of cerebral ischemia and diabetic ischemia on astrocytes and oligodendrocytes have not been defined. The objective of this study is to define profile of astrocyte and changes of myelin in diabetic and non-diabetic rats subjected to focal ischemia.Focal cerebral ischemia of 30-min duration was induced in streptozotocin-induced diabetic and vehicle-injected normoglycemic rats. The brains were harvested for immunohistochemistry of glial fibrillary acidic protein (GFAP) and 2'', 3''-cyclic nucleotide 3''-phosphodiesterase (CNPase) at various reperfusion endpoints ranging from 30 min up to 28 days. The results showed that activate astrocytes were observed after 30 min and peaked at 3 h to 1 day after reperfusion in ischemic penumbra, and peaked at 7 days of reperfusion in ischemic core. Diabetes inhibited the activation of astrocytes in ischemic hemisphere. Demyelination occurred after 30 min of reperfusion in ischemic core and peaked at 1 day. Diabetes caused more severe demyelination compared with non-diabetic rats. Remyelination started at 7 days and completed at 14 and 28 days in ischemic region. Diabetes inhibited the remyelination processes. It is concluded that ischemia activates astrocytes and induces demyelination. Diabetes inhibits the activation of astrocytes, exacerbates the demyelination and delays the remyelination processes. These may contribute to the detrimental effects of hyperglycemia on ischemic brain damage.     

大鼠视网膜变性相关组织形态及功能研究

目的　探讨视网膜变性RCS (RoyalCollegeSurgeon)大鼠的视网膜形态及功能特点。 方法　应用HE染色、免疫组化染色和眼电生理技术 ,对比研究正常和变性两组大鼠视网膜特点。结果　 1 RCS大鼠在 3月龄时 ,视网膜外核层和感光细胞内外节完全消失 ;突触素免疫组化染色显示外丛状层不着色 ;视紫红质免疫组化染色显示原视网膜外层部位有阳性反应 ;胶质纤维酸性蛋白染色显示原视网膜外层部位有强阳性反应。 2 RCS大鼠的闪光视网膜电图 (flashelectronicretinogram ,FERG)a、b波振幅较正常Wistar大鼠明显降低 (P <0 0 1)。结论　在形态和功能上 ,3月龄RCS大鼠视网膜与人类晚期视网膜色素变性极为相似 ,因此可用于视网膜联合移植研究。     

Risk Factors and Mechanisms of Cardiovascular Diseases in Posttraumatic Stress Disorder Model in Wistar Rats as Dependent on Stress Resistance and Age

Doklady Biological Sciences - The article focuses on the pathogenetic mechanisms of posttraumatic stress disorder (PTSD), which is associated with psychological stress because of the coronavirus...     

Coronary Artery Ligation and Intramyocardial Injection in a Murine Model of Infarction

Mouse models are a valuable tool for studying acute injury and chronic remodeling of the myocardium in vivo. With the advent of genetic modifications to the whole organism or the myocardium and an array of biological and/or synthetic materials, there is great potential for any combination of these to assuage the extent of acute ischemic injury and impede the onset of heart failure pursuant to myocardial remodeling. Here we present the methods and materials used to reliably perform this microsurgery and the modifications involved for temporary (with reperfusion) or permanent coronary artery occlusion studies as well as intramyocardial injections. The effects on the heart that can be seen during the procedure and at the termination of the experiment in addition to histological evaluation will verify efficacy. Briefly, surgical preparation involves anesthetizing the mice, removing the fur on the chest, and then disinfecting the surgical area. Intratracheal intubation is achieved by transesophageal illumination using a fiber optic light. The tubing is then connected to a ventilator. An incision made on the chest exposes the pectoral muscles which will be cut to view the ribs. For ischemia/reperfusion studies, a 1 cm piece of PE tubing placed over the heart is used to tie the ligature to so that occlusion/reperfusion can be customized. For intramyocardial injections, a Hamilton syringe with sterile 30gauge beveled needle is used. When the myocardial manipulations are complete, the rib cage, the pectoral muscles, and the skin are closed sequentially. Line block analgesia is effected by 0.25% marcaine in sterile saline which is applied to muscle layer prior to closure of the skin. The mice are given a subcutaneous injection of saline and placed in a warming chamber until they are sternally recumbent. They are then returned to the vivarium and housed under standard conditions until the time of tissue collection. At the time of sacrifice, the mice are anesthetized, the heart is arrested in diastole with KCl or BDM, rinsed with saline, and immersed in fixative. Subsequently, routine procedures for processing, embedding, sectioning, and histological staining are performed. Nonsurgical intubation of a mouse and the microsurgical manipulations described make this a technically challenging model to learn and achieve reproducibility. These procedures, combined with the difficulty in performing consistent manipulations of the ligature for timed occlusion(s) and reperfusion or intramyocardial injections, can also affect the survival rate so optimization and consistency are critical.     

SPF级近交系Wistar大鼠繁殖性能的观察

目的对近交系Wistar大鼠进行繁殖性能的测定。方法选取血缘扩大群共18对,90日龄开始按1♀＊1♂进行交配,统计其生长繁殖性能。结果第二、三、四胎的平均窝产仔数和断奶窝重比第一和第五胎高。第一胎仔鼠从出生第3天到第7天（增重9．42g）、第14天到第21天（13．98g）快速生长。母鼠怀孕期、哺乳期体重、饲料和水的日消耗量有明显的差异,母鼠哺乳期饲料和水的日消耗量均比怀孕期高,母鼠怀孕期体重明显比哺乳期重,母鼠怀孕期体重后期比初期增加150g左右,曲线呈上升趋势。结论本群Wistar近交系大鼠的生长繁殖符合近交系大鼠的生长繁殖规律。     

SD大鼠和Wistar大鼠实验性自身免疫性脑脊髓炎发病情况比较

目的比较Wistar大鼠和Sprague-Dawley（SD）大鼠实验性自身免疫性脑脊髓炎（EAE）发病情况。方法注射以豚鼠脊髓匀浆-完全福氏佐剂制备的完全抗原,辅以百日咳疫苗加强诱导,复制Wistar大鼠和SD大鼠EAE模型,比较两组大鼠EAE的神经症状及中枢神经不同部位病理学改变。结果Wistar大鼠组发病数、潜伏期、发病达峰时间以及神经症状最高评分分别为9/12、12.33±1.37、15.17±3.19、1.33±0.41;SD大鼠组分别为11/12、15.88±0.64、18.63±1.52、3.13±1.89;两组大鼠相比,SD大鼠EAE潜伏期延长（P〈0.01）,达峰时间相应推迟（P〈0.05）,但神经症状较Wistar大鼠严重（P〈0.05）;病理结果显示,两组大鼠CNS均以脑干病理改变最为严重,而大脑病变最轻,SD大鼠总体中枢系统炎症改变较Wistar大鼠严重（标准评分P〈0.01,血管套计数P〈0.05）。结论SD大鼠EAE与Wistar大鼠EAE比较,发病过程很相似：发病率接近,中枢炎症病理改变相仿,两者均以脑干炎症变化最严重;略有不同点是：SD大鼠EAE发病潜伏期较长（P〈0.01）,神经症状较严重（P〈0.05）,总体中枢炎症改变较为严重。故SD大鼠也是制备EAE模型的理想实验动物。     

Wistar大鼠心脏自发性病变的病理学观察

目的了解Wistar大鼠心脏自发性病变发病情况,为长期致癌性研究、老年病学研究及毒性病理学提供背景资料。方法采用160只清洁级Wistar大鼠,雌雄各半,常规饲养,分别在9月龄、12月龄、18月龄、24月龄时处死40只大鼠,HE及Masson三色法染色,观察心脏的病理改变。结果 9月龄Wistar大鼠心脏未见明显病理改变;12月龄Wistar大鼠月龄心脏病变的发病率为2.5%（1/40）,表现为少数心肌细胞变性坏死伴少量以单核细胞为主的炎细胞浸润;18月龄大鼠心脏病变的发病率为57.5%（23/40）,表现为轻至中度心肌病,雄性发病率高于雌性。24月龄大鼠100%（40/40）出现不同程度的心肌病,并有2.5%（1/40）发生心内膜下纤维组织增生。Masson染色显示9月龄大鼠心脏血管周围及心脏瓣膜环下有少量胶原纤维,随年龄增长,血管周围及心脏瓣膜环下胶原纤维逐渐增多,并延伸入心肌细胞间。结论随年龄增长,大鼠心脏自发病变比率升高,主要病变为心肌病,偶尔可发生心内膜下纤维组织增生;胶原纤维沉积首先发生于血管周围及心脏瓣膜环下,随年龄增长而增多,可能与大鼠心肌病的的发生密切相关。     

Wistar大鼠胶原诱导的关节炎造模因素的分析

目的通过比较不同的造模方法,分析影响胶原诱导关节炎（collagen-induced arthritis,CIA）大鼠模型建立的因素。方法选用Wistar大鼠造模,通过改变性别、剂量、年龄、注射部位及免疫方式,来比较造模成功率。结果不同性别、剂量、年龄及免疫方式造模成功率不同。结论4～5周龄Wistar雌性大鼠,初次免疫注射乳剂4点共0.20 mL,加强免疫在14 d之后3点共0.15 mL的造模成功率最高。     

Universal Temporal Profile of Replication Origin Activation in Eukaryotes

Although replication proteins are conserved among eukaryotes, the sequence requirements for replication initiation differ between species. In all species, however, replication origins fire asynchronously throughout S phase. The temporal program of origin firing is reproducible in cell populations but largely probabilistic at the single-cell level. The mechanisms and the significance of this program are unclear. Replication timing has been correlated with gene activity in metazoans but not in yeast. One potential role for a temporal regulation of origin firing is to minimize fluctuations in replication end time and avoid persistence of unreplicated DNA in mitosis. Here, we have extracted the population-averaged temporal profiles of replication initiation rates for S. cerevisiae, S. pombe, D. melanogaster, X. laevis and H. sapiens from genome-wide replication timing and DNA combing data. All the profiles have a strikingly similar shape, increasing during the first half of S phase then decreasing before its end. A previously proposed minimal model of stochastic initiation modulated by accumulation of a recyclable, limiting replication-fork factor and fork-promoted initiation of new origins, quantitatively described the observed profiles without requiring new implementations.The selective pressure for timely completion of genome replication and optimal usage of replication proteins that must be imported into the cell nucleus can explain the generic shape of the profiles. We have identified a universal behavior of eukaryotic replication initiation that transcends the mechanisms of origin specification. The population-averaged efficiency of replication origin usage changes during S phase in a strikingly similar manner in a highly diverse set of eukaryotes. The quantitative model previously proposed for origin activation in X. laevis can be generalized to explain this evolutionary conservation.     

HFJ和Wistar大鼠脂肪肝及胰岛素抵抗动物模型的比较

目的建立近交系HFJ大鼠和封闭群Wistar大鼠脂肪肝胰岛素抵抗动物模型及比较其生物学特性。方法雄性HFJ大鼠和Wistar大鼠,分别随机分为模型组和正常组,模型组喂养高脂饮食,正常组喂养普通饮食,两组脂肪分别占摄入能量的44.2%和19.2%,共饲养12周。每周称体质量,测定血糖、甘油三酯、胆固醇、ALT、AST、HDLC、LDLC和血胰岛素水平。实验期末处死动物摘取肝脏并称质量,计算肝指数;鼠肝脏用10%甲醛固定,石蜡包埋切片,HE染色,光镜下评估肝脂肪变性和炎症活动情况。结果镜下可见,HFJ和Wistar大鼠模型组肝细胞均呈现弥漫性脂肪变性,小叶内可见炎症细胞浸润,HFJ比Wistar脂肪变性较重,对照组肝脏均未见异常。两种动物的模型组ALT、AST、肝指数、HOMA-IR指数均显著高于其正常组,HFJ和Wistar种系间各指标的差异无显著性;HFJ大鼠模型组体重和正常组体重具有显著性差异(P<0.01),而Wistar大鼠模型组体重与正常组体重间无显著差异(P>0.05);HFJ大鼠TG和TC含量均显著高于Wistar大鼠。结论通过高脂饮食喂养成功建立了HFJ大鼠和Wistar大鼠脂肪肝与胰岛素抵抗疾病动物模型,与Wistar大鼠比较,HFJ大鼠具有自发性高血脂特征,造模更易成功,可为胰岛素抵抗和脂肪肝的发病机制研究、防治高血脂药物筛选提供一种新的实验动物。     

Tracing of Zinc Nanocrystals in the Anterior Pituitary of Zinc-Deficient Wistar Rats

The aim of this study was to trace zinc nanocrystals in the anterior pituitary of zinc-deficient Wistar rats by using autometallographic technique. Male Wistar rats (30–40 days of age, pre-pubertal period) of 40–50 g body weight were divided into the following: the ZC (zinc control) group—fed with 100 ppm zinc in diet, the ZD (zinc-deficient) group—fed with zinc-deficient (1.00 ppm) diet and the PF (pair-fed) group—received 100 ppm zinc in diet. The experiments were set for 2 and 4 weeks. Pituitary was removed and processed for the autometallographic technique. The control and pair-fed groups retained their normal morphological features. However, male Wistar rats fed on zinc-deficient diet for 2 and 4 weeks displayed a wide range of symptoms such as significant (P < 0.05) decrease in diet consumption, body weight and pituitary weight and decrease in gradation of intensity of zinc nanocrystals in the nuclei. The present findings suggest that the dietary zinc deficiency causes decreased intensity of zinc nanocrystals localization and their distribution in the pituitary thereby contributing to the dysfunction of the pituitary of the male Wistar rats. The severity of zinc deficiency symptoms progressed after the second week of the experiment. Decreased intensity of zinc nanocrystals attenuates the pituitary function which would exert its affect on other endocrine organs impairing their functions indicating that the metabolic regulation of pituitary is mediated to a certain extent by zinc and/or hypothalamus-hypophysial system which also reflects its essentiality during the period of growth.     

冠脉结扎和介入两种方法制备犬心肌梗死模型的比较

目的观察开胸结扎冠状动脉与闭胸明胶海绵栓塞法制备急性心肌梗死（AMI）动物模型的特点。方法分别经开胸结扎犬冠状动脉左前降支主干及闭胸冠脉栓塞的方法阻断冠脉血流;采用单级肢体导联和胸导联方式,在阻断前后监测心电图波形变化;造模72h后取心肌组织行病理切片染色。结果经心电图和病理验证,两种方法均可成功制备犬心梗模型,开胸冠脉结扎犬死亡率较高,而冠脉栓塞成活率高。结论相较开胸冠脉结扎法,闭胸栓塞法制备心梗模型对动物损伤小,成活率高,具推广价值。     

链脲佐菌素诱导SD和Wistar大鼠糖尿病模型的影响因素

目的通过注射链脲佐菌素（STZ）制作SD和Wistar大鼠糖尿病模型,观察大鼠品系、给药剂量、给药次数对大鼠成模率、死亡率的影响,同时研究利用口服葡萄糖耐量试验（OGTT）判断大鼠糖尿病成模率的意义。方法设置共同的正常对照组,①Wistar大鼠随机分为中剂量组（55 mg/kg）和高剂量组（65 mg/kg）;②SD大鼠一次性腹腔注射STZ（55 mg/kg）,与①中的Wistar大鼠作对比;③SD大鼠随机分为一次给药组和两次给药组,注射剂量均为55 mg/kg,观察期间进行OGTT。结果①Wistar大鼠成模率和死亡率均高于SD大鼠;②采用SD大鼠、中剂量给药和两次给药的方式可提高成模率,并降低死亡率;③在有明确胰岛病理改变的模型组大鼠,其OGTT异常阳性率显著高于空腹血糖异常阳性率。结论用STZ诱导糖尿病模型是一种稳定可靠的方法。Wistar大鼠成模率和死亡率均高于SD大鼠;选用中剂量给药及两次给药的方式可提高SD大鼠成模率,并降低死亡率,维持时间较长。在动物实验中OGTT比空腹血糖监测更有诊断意义,不易造成漏诊。     

辽宁地区普通级和SPF级Wistar大鼠血液生化指标检测

目的建立本省、本地区实验动物生理指标数据背景资料,为科学研究和新药安全性评价提供准确、可靠、科学的参考依据。方法普通级、SPF级Wistar大白鼠（6～8周龄）各60只,雌雄各半,腹主动脉采血,用全自动生化分析仪及配套试剂盒检测血液生化指标。结果普通级Wistar大白鼠的ALT、ALP、CHO、CK、CRE雌雄之间差异显著（P〈0．05或P〈0．01）;SPF级Wistar大白鼠的ALB、ALT、ALP、CHO、BUN、CK、AST、GLU、TBIL雌雄之间差异显著（P〈0．05或P〈0．01）;普通级与SPF级Wistar大白鼠的ALT、ALP、TP、BUN、TBIL、CRE、CHO、CK、AST、ALB、GLU差异显著（P〈0．01）。结论本研究的结果证明普通级与SPF级Wistar大白鼠的血液生化指标差异显著,多数生化指标雌雄之间存在显著差异,为应用提供了有价值的参数。