高尿酸血症肾病的实验动物模型研究

以酵母、腺嘌呤饲料喂养SD大鼠,观察大鼠血清中尿酸、肌酐、尿素氮含量的动态变化以及停用该饲料后大鼠自然恢复情况,同时观察大鼠肾脏病理改变.结果用高酵母、腺嘌呤饲料喂养19d,大鼠血清中尿酸、肌酐、尿素氮明显升高(P＜0.01),肾脏出现与临床痛风性肾病相类似的病理改变.停用酵母、腺嘌呤饲料后,大鼠有自然恢复趋势,但周期较长(＞ 52d).     

糖心宁胶囊治疗糖尿病性冠心病的实验研究

目的：探讨糖心宁胶囊治疗糖尿病性冠心病的作用机理。方法：采用链佐菌素造高血糖大鼠模型。并对高血糖大鼠模型进行冠脉结扎术造心肌缺血模型。结果：糖心宁胶囊能显著降低高血糖模型大鼠空腹血糖,提高其胰岛素分泌能力,降低其总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白（LDL）水平,升高高密度脂蛋白水平（HDL）,并能够明显改善心肌缺血模型大鼠心肌缺血状态,结论：糖心宁胶囊具有清除脂质过氧化物,对抗或消除动脉粥样硬化斑块的作用。能显著改善冠脉左前降支结扎引起的心肌缺血大鼠的异常心电图,延长其存活时间。     

大鼠运动力竭后生理生化因素对PWN粘弹性影响的实验研究

本文利用微吸管实验方法，研究了ｐＨ值，乳酸，肾上腺素和能量物质对大鼠运动力竭前后多形核中性粒细胞（Ｐｏｌｙｍｏｒｐｈｏｎｃｌｅａｒ ｎｅｕｔｒｏｐｈｉｌｓ，ＰＭＮｓ）粘弹性的影响。结果发现随着乳酸浓度、肾上腺素浓度的增加，大鼠ＰＭＮ粘弹性参数发生不同程度的增加，变形性发生相应的变化；随着ｐＨ值从 ７．４下降到６．４，ＰＭＮ粘弹性参数逐渐增大；但是ＰＭＮ粘弹性不受葡萄糖和ＡＴＰ浓度的影响。     

中药喘可治对小鼠胸腺细胞抗凋亡作用研究

目的:研究中药喘可治(CKZ)对小鼠胸腺细胞的抗凋亡作用。方法:以地塞米松(DEX )诱导小鼠胸腺细胞凋亡建模,以CKZ保护小鼠胸腺细胞;6h时点以AnnexinV -FITC/PI双染流式细胞术检测早期凋亡和坏死细胞、以PI染色流式细胞术检测晚期凋亡。结果:CKZ +DEX组早期凋亡比率(3 5 2 9±2 73 ) %显著低于DEX组(4 5 97±1 3 9) %(P <0 0 1) ;该两组坏死细胞比率差异不显著。DEX +CKZ组晚期凋亡百分率为(17 2 6±4 5 8) % ,显著低于CKZ组(3 3 88±5 61) % (P <0 0 1)。上述各组数据与对照组差异显著(P <0 0 1)。结论:CKZ可以显著的抑制DEX诱导的小鼠胸腺细胞早期和晚期凋亡     

Clinical and Histopathologic Features of a Feline SARS-CoV-2 Infection Model Are Analogous to Acute COVID-19 in Humans

The emergence and ensuing dominance of COVID-19 on the world stage has emphasized the urgency of efficient animal models for the development of therapeutics for and assessment of immune responses to SARS-CoV-2 infection. Shortcomings of current animal models for SARS-CoV-2 include limited lower respiratory disease, divergence from clinical COVID-19 disease, and requirements for host genetic modifications to permit infection. In this study, n = 12 specific-pathogen-free domestic cats were infected intratracheally with SARS-CoV-2 to evaluate clinical disease, histopathologic lesions, and viral infection kinetics at 4 and 8 days post-inoculation; n = 6 sham-inoculated cats served as controls. Intratracheal inoculation of SARS-CoV-2 produced a significant degree of clinical disease (lethargy, fever, dyspnea, and dry cough) consistent with that observed in the early exudative phase of COVID-19. Pulmonary lesions such as diffuse alveolar damage, hyaline membrane formation, fibrin deposition, and proteinaceous exudates were also observed with SARS-CoV-2 infection, replicating lesions identified in people hospitalized with ARDS from COVID-19. A significant correlation was observed between the degree of clinical disease identified in infected cats and pulmonary lesions. Viral loads and ACE2 expression were also quantified in nasal turbinates, distal trachea, lungs, and other organs. Results of this study validate a feline model for SARS-CoV-2 infection that results in clinical disease and histopathologic lesions consistent with acute COVID-19 in humans, thus encouraging its use for future translational studies.     

Development of thrombopoietin receptor agonists for clinical use

Summary.  Thrombopoietin (TPO) is an essential hematopoietic cytokine for megakaryopoiesis. In 2002, we demonstrated that pegylated-recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) increased platelet counts in patients with chronic immune thrombocytopenic purpura (ITP) in a Phase I/II clinical trial. After the cessation of clinical trials of PEG-rHuMGDF because of severe thrombocytopenia or pancytopenia due to the development of the neutralizing antibody cross-reacting with endogenous TPO, second generation non-immunogenic TPO receptor agonists have been developed. A small molecule eltrombopag and Romiplostim were approved for clinical use by FDA in 2008 to treat patients with chronic ITP who are refractory to the prior therapy. Although the efficacy of both TPO receptor agonists is convincing for the refractory ITP, further investigation is necessary to assess the potential long-term side effects and clinical applications of these therapies for other thrombocytopenic conditions.     

大鼠急性心肌缺血后心肌细胞凋亡的研究

目的探讨早期心肌缺血心肌细胞凋亡的意义。方法采用末端脱氧核糖核酸酶标记法（TUNEL）对大鼠实验性心肌缺血早期内（6 h内）不同时间缺血损伤区心肌细胞凋亡的情况进行观察。结果缺血30 min在缺血区域发现少数散在的凋亡阳性细胞,3 h达高峰,随后下降。正常区域未发现凋亡细胞。缺血边缘区域也在缺血1 h局部开始出现心肌细胞凋亡,并随缺血时间延长心肌细胞凋亡指数增加,缺血5 h达高峰。结论大鼠心肌缺血后,缺血区及其边缘区均有心肌细胞凋亡发生,表明凋亡是早期缺血性心肌细胞损伤的主要方式。     

Reflux injury of esophageal mucosa: experimental studies in animal models of esophagitis, Barrett''s esophagus and esophageal adenocarcinoma

Barrett's esophagus (BE), a gastroesophageal reflux associated complication, is defined as the replacement of normal esophageal squamous mucosa by specialized intestinal columnar mucosa with the appearance of goblet cells. The presence of BE is associated with an increased risk of developing esophageal adenocarcinoma (EAC). Although the exposure of gastroduodenal contents to the esophageal mucosa is considered to be an important risk factor for the development of esophagitis, BE and EAC, the mechanisms of reflux esophageal injury are not fully understood. Animal models are now being used extensively to identify the mechanisms of damage and to devise protective and mitigating strategies. Experimental studies on animal models by mimicking the processing of gastroesophageal reflux injury have bloomed during the past decades, however, there is controversy regarding which experimental model for reflux esophagitis, experimental BE and experimental EAC is best. In this review article we aim to clarify the basic understanding of gastroesophageal reflux injury and its complications of BE and EAC, as well as to present current understanding of the reflux experimental models. The animal models of experimental esophageal injury are summarized with focus on the surgical procedures to guide the investigator in choosing or developing a correct animal model in future studies. In addition, our own experimental studies of the animal models are also briefly discussed.     

在大鼠关节滑膜细胞表达人白细胞介素10的基因转移系统的建立

目的 建立一个在大鼠关节滑膜细胞表达人白细胞介素１０（ｈｕｍａｎ ｉｎｔｅｒｌｅｕｋｉｎ１０,ｈＩＬ－１０）的重组逆转录病毒载体基因转移系统,为下一步的研究工作做准备。方法 构建表达人白细胞介素１０的 转灵病毒重组体的ｐＬＸ（ｈＩＬ－１０）ＳＮ,经ＰＡ３１７细胞包装,Ｇ４１８筛选,ＮＩＨ３Ｔ３细胞进行病毒滴度测定,选滴度最高的克隆（６×１０＾８集落形成单位／Ｌ）作为感染大鼠关节滑膜细胞的感染细胞;     

In vivo relevance for platelet glycoprotein Ibα residue Tyr276 in thrombus formation

Summary.  Background:  Platelet glycoprotein (GP) Ib-IX-V supports platelet adhesion on damaged vascular walls by binding to von Willebrand factor (VWF). For several decades it has been recognized that the α-subunit of GP (GPIbα) also binds thrombin but the physiological relevance, if any, of this interaction was unknown. Previous studies have shown that a sulfated tyrosine 276 (Tyr276) is essential for thrombin binding to GPIbα. Objectives:  This study investigated the in vivo relevance of GPIbα residue Tyr276 in hemostasis and thrombosis. Methods:  Transgenic mouse colonies expressing the normal human GPIbα subunit or a mutant human GPIbα containing a Phe substitution for Tyr276 (hTg^Y276F) were generated. Both colonies were bred to mice devoid of murine GPIbα. Results:  Surface-expressed GPIbα levels and platelet counts were similar in both colonies. hTg^Y276F platelets were significantly impaired in binding α-thrombin but displayed normal binding to type I fibrillar collagen and human VWF in the presence of ristocetin. In vivo thrombus formation as a result of chemical damage (FeCl₃) demonstrated that hTg^Y276F mice have a delayed time to occlusion followed by unstable blood flow indicative of embolization. In models of laser-induced injury, thrombi developing in hTg^Y276F animals were also less stable. Conclusions:  The results demonstrate that GPIbα residue Tyr276 is physiologically important, supporting stable thrombus formation in vivo .