去甲斑蝥素对蛋白负荷肾病大鼠干预的研究

目的 观察去甲斑蝥素对蛋白负荷肾病大鼠蛋白尿及肾脏病理的影响。 方法 摘除SD大鼠右肾，腹腔注射牛血清白蛋白，建立蛋白负荷肾病模型后分成模型组和去甲斑蝥素组；对照组仅注射生理盐水。检测各时间点各组大鼠尿蛋白定量（24 h）。第5周末处死大鼠，检测血常规及生化指标；肾组织行光镜、电镜及免疫荧光染色作病理学检查。 结果 与对照组比较，模型组肾重/体重、各时间点尿蛋白定量（24 h）、肾小球硬化指数、小管间质病理损伤积分均显著升高（P均 ＜ 0.01）， 血清白蛋白（Alb）显著降低（P ＜ 0.01)。电镜结果显示模型组小鼠肾小球系膜区有明显电子致密物沉积，足突融合；免疫荧光显示IgG和C3沉积于系膜区（3+～4+）。去甲斑蝥素干预后，肾病大鼠除Alb升高（P ＜ 0.01）外，上述其余指标均显著降低（P ＜ 0.05或0.01)；系膜区有散在电子致密物沉积，足突灶状融合；IgG和C3免疫荧光染色强度减弱。各组间Scr、BUN、ALT及血常规差异均无统计学意义。 结论 去甲斑蝥素能显著降低蛋白负荷肾病大鼠尿蛋白，减轻其肾小管间质病理损伤，且无肝肾毒性及骨髓抑制等严重不良反应。     

三种实验性IgA肾病模型的比较

目的探讨建立一种理想的IgA肾病（IgAN）动物模型方法。方法分别采用葡聚糖G200、大肠杆菌外膜蛋白和金葡菌的细胞膜20肽抗原决定簇诱导小鼠IgA肾病模型。用分子生物学和病理学方法对3组IgAN模型小鼠进行鉴定和比较。结果（1）葡聚糖组尿蛋白增高，伴有血尿；免疫荧光显示部分肾小球大量IgA沉积；光镜下肾小球系膜细胞增多，肝和脾可见弥漫性的粉染物质沉积；电镜下肾小球系膜区少量低电子密度的致密沉积物，肝和脾可见淀粉丝样物质沉积。（2）大肠杆菌外膜蛋白组尿蛋白增高，伴有血尿；免疫荧光显示肾小球有少量IgA沉积；光镜下肾小球系膜细胞轻度增多，间质炎细胞浸润明显；电镜下肾小球系膜区无电子致密沉积物。（3）金葡菌细胞膜20肽抗原决定簇组尿蛋白增高，伴有血尿；免疫荧光显示多数肾小球均可见大量IgA沉积；光镜下肾小球系膜细胞增多，伴系膜基质轻度增生；电镜下肾小球系膜区和基底膜的内皮细胞下可见高电子密度的致密沉积物。结论金葡菌细胞膜20肽抗原决定簇组诱导的IgAN模型从临床表现和病理学变化与人IgAN极其相似，是3种IgAN模型中最理想的IgAN模型。     

不同深度糖尿病大鼠烫伤模型的制备

目的探讨恒温恒压电热烫伤仪制作糖尿病大鼠不同深度烫伤模型的可行性。方法链脲佐菌素诱导正常SD大鼠制作糖尿病大鼠模型，诱导成功1、2、3、4周检测皮肤晚期糖基化终产物、胶原含量，以正常SD大鼠作为对照，判断典型糖尿病性皮肤改变所需的时间。以恒温恒压烫伤仪制作烫伤模型，制模条件为0．5kg压力下，80℃，分别作用时间4．6、12s，48h后取材行苏木素-伊红（HE）染色检测烫伤深度。结果糖尿病大鼠诱导成功后4周，皮肤晚期糖基化终产物含量为（31．40±3．45）U／mg、胶原含量为（12．60±0．57）mg／g，与正常对照组比较差异有统计学意义（P〈0．05），并出现典型的糖尿病性皮肤改变。HE染色烫伤时间4、6、12s时深度依次为浅Ⅱ度、深Ⅱ度和Ⅲ度。结论恒温恒压电热烫伤仪制作糖尿病大鼠不同深度烫伤模型简单、方便，重复性高，为研究糖尿病创面愈合提供较为理想的模型。     

大鼠视神经损伤定量模型的建立

目的建立标准化视神经损伤大鼠动物模型，对致伤强度、损伤程度及两者之间的关系进行量化分析。方法在立体定位下，利用微电极毁损视神经颅内段，毁损电压为5V，频率为60kHz，通过改变电毁损的电流强度，造成不同程度视神经损伤。然后进行视网膜切片，计数视神经节细胞层细胞，定量视神经损伤。结果析因方差分析结果显示：视神经节细胞计数存不同刺激时间之间，差异硅著（F=3472，14，P〈0．001）；在不同电流强度组间，差异显著（F=335．83，P〈0．001）；经LSD法多重比较，视神经节细胞计数在刺激电流之间及刺激时间之间差异在α=0．05水平均有显著性意义。刺激强度和刺激时间的单独效应：同一电流组随着刺激时间增加．视神经节细胞计数呈下降趋势；除对照组和90s组外（F=0．79，P=0．548；F=1．54，P=0．242），刺激时间相同时，随电流强度增加．细胞计数也呈下降趋势，刺激电流强度与刺激时间之间交互效廊显著（F=27．30，P〈0．001）：结论立体定向电毁损大鼠颅内段视神经模型可以测定致伤强度和视神经损伤程度，是较理想的视神经损伤模型。     

动脉瘤模型栓塞前后血流动力学对比研究

目的 评价动脉瘤模型行腔内微弹簧圈栓塞前后血流动力学的改变，用以判断疗效。方法 运用改进的显微外科技术建立犬颈总动脉（CCA）动脉瘤模型22个，其中侧壁型12个，分叉部4个，末端型6个。术后7～14d行彩色多普勒超声、经颅多普勒（TCD）、数字减影动脉血管造影（IADSA）及经微导管动脉瘤内测压，然后以微弹簧圈紧密填塞动脉瘤腔，栓塞后重复进行上述检查，比较栓塞前后血流动力学变化。结果 所建模型均获成功。实验证实，动脉瘤微弹簧圈栓塞前后其血流动力学参数的差异有统计学意义（P〈0．01）。结论 实验所建动物模型是研究动脉瘤血管内栓塞治疗的理想方法；动脉瘤微弹簧圈栓塞后，能减低、改变或消除载瘤动脉及动脉瘤内异常血流动力学状态，终止动脉瘤行为，防止动脉瘤扩大和破裂。     

Assessing the Stiffness of Spinal Fusion in Animal Models

The clinical goal of spinal fusion is to reduce motion and the associated pain. Therefore, measuring motion under loading is critical. The purpose of this study was to validate four-point bending as a means to mechanically evaluate simulated fusions in dog and rabbit spines. We hypothesized that this method would be more sensitive than manual palpation and would be able to distinguish unilateral vs bilateral fusion. Spines from four mixed breed dogs and four New Zealand white rabbits were used to simulate posterolateral fusion with polymethyl methacrylate as the fusion mass. We performed manual palpation and nondestructive mechanical testing in four-point bending in four planes of motion: flexion, extension, and right and left bending. This testing protocol was used for each specimen in three fusion modes: intact, unilateral, and bilateral fusion. Under manual palpation, all intact spines were rated as not fused, and all unilateral and bilateral simulated fusions were rated as fused. In four-point bending, dog spines were significantly stiffer after unilateral fusion compared with intact in all directions. Additionally, rabbit spines were stiffer in flexion and left bending after unilateral fusion. All specimens exhibited significant differences between intact and bilateral fusion except the rabbit in extension. For unilateral vs bilateral fusion, significant differences were present for right bending in the dog model and for flexion in the rabbit. Unilateral fusion can provide enough stability to constitute a fused grade by manual palpation but may not provide structural stiffness comparable to bilateral fusion.     

大鼠肝细胞凋亡和坏死动物模型的建立及评价

目的:通过大鼠肝右叶血供干预分别建立肝细胞凋亡和坏死动物模型,为进一步的磁共振成像实验奠定基础。方法:选取体重为250-300克的SD大鼠90只,随机分为A、B、C三组,每组30只,分别行肝右叶门静脉和肝动脉结扎术、门静脉结扎术及假手术,各组在术后3 h及1、3、7和14 d分别处死6只大鼠,取肝脏标本送病理及电镜检查。结果: A组30只大鼠肝右叶发生凝固性坏死,光镜及电镜下均呈典型的坏死改变,TUNEL染色呈阴性;B组30只大鼠肝右叶发生小灶性凋亡,光镜下可见肝细胞核固缩改变,电镜下见肝组织核边集和凋亡小体,TUNEL染色呈阳性改变。术后3 h 即可见凋亡细胞,24 h时凋亡细胞数最多,7 d后肝组织开始发生小灶性坏死;C组30只大鼠肝右叶未发生凋亡和坏死的病理改变。结论:大鼠肝右叶门静脉和肝动脉双结扎可建立胆脏凝固性坏死模型,单纯肝右叶门静脉结扎能构建肝细胞小灶性凋亡模型。     

Safety of, and biological and functional response to, a novel metallic implant for the management of focal full-thickness cartilage defects: Preliminary assessment in an animal model out to 1 year.

Focal full-thickness cartilage lesions of the human medial femoral condyle (MFC) can cause pain and functional impairment. Affected middle-aged patients respond unpredictably to existing treatments and knee arthroplasty may be required, prompting risk of revision. This study assesses the safety of, and biological and functional response to, a metallic resurfacing implant which may delay or obviate the need for traditional arthroplasty. The anatomic contour of the surgically exposed MFC of six adult goats was digitally mapped and an 11 mm diameter full-thickness osteochondral defect was created. An anchor-based Co-Cr resurfacing implant, matching the mapped articular contour, was implanted. Each goat's contralateral unoperated femorotibial joint was used as a control. Postoperative outcome was assessed by lameness examination, radiography, arthroscopy, synoviocentesis, necropsy, and histology up to 26 (n = 3) or 52 (n = 3) weeks. By postoperative week (POW) 4, goats demonstrated normal range of motion, no joint effusion, and only mild lameness in the operated limb. By POW 26 the animals were sound with only occasional very mild lameness. Arthroscopy at POW 14 revealed moderate synovial inflammation and a chondral membrane extending centrally across the implant surface. Radiographs at POWs 14 to 52 implied implant stability in the operated joints, as well as subchondral bone remodeling and mild exostosis formation in the operated and contralateral unoperated joints of some goats. By POW 26, histology revealed new trabecular bone abutting the implant. At POWs 26 and 52 MFC cartilage was metachromatic and intact in the operated and unoperated femorotibial joints. Proximal tibiae of some operated and unoperated limbs demonstrated limited subchondral bone remodeling and foci of articular cartilage fibrillation and thinning. The chondral membrane crossing the prosthesis possessed a metachromatic matrix containing singular and clustered chondrocytes. Our data imply the safety, biocompatibility, and functionality of the implant. Focal articular damage was documented in the operated joints at POWs 26 and 52, but lesions were much reduced over those previously reported in untreated defects. Expanded animal or preclinical human studies are justified.     

血管性勃起功能障碍动物模型的建立

目的探索建立血管性勃起功能障碍(ED)动物模型。方法雄性新西兰大白兔给予胆固醇及高脂饮食,同时用球囊导管损伤双侧髂内动脉内皮。测定术后4周、8周血脂并观察阴茎勃起情况、交配情况,同时用阴茎海绵体注射盐酸罂粟碱、阴茎血管双核素检查、髂内动脉数字减影造影(DSA)等方法研究勃起功能。结果与对照组相比,术后4周、8周模型组动物出现明显高脂血症,勃起程度明显下降,交配实验的各项观察指标均显著降低(P＜0.01),动脉造影显示双侧髂内动脉管腔直径明显缩小,双核素检查动脉显像指数(PIA)及静脉显像指数(PIV)明显降低,但第4周的模型组与对照组PIV结果没有统计学差异(P＞0.05)。结论高脂、高胆固醇饮食同时用球囊导管扩张动物髂内动脉,可以加速模型的形成,从而用于血管性ED的进一步研究。     

低压状态下猪鼾症模型的建立及其CT研究

目的探讨低压环境对动物上气道软组织形态学的影响。方法将试验猪置于一个低压环境饲养6个月建立猪的鼾症模型,当出现类似鼾症临床症状和鼾症相似的咽腔压力波形时,再进行CT扫描影像学检查。并与正常状态饲养的对照组进行对比。结果模型猪咽后壁及软腭明显增厚,分别为(0.94±0.16)cm和(1.06±0.23)cm;对照组分别为(0.60±0.11)cm和(0.59±0.13)cm。模型猪的气管截面积在在前、中、后部分别为(1.49±0.12)cm2、(1.37±0.32)cm2和(1.00±0.21)cm2,其中以悬雍垂水平(后部)最为狭窄;对照组前、中、后部分别为(1.30±0.14)cm2、(1.57±0.32)cm2和(2.48±0.42)cm2。结论低压状态是鼾症的重要的致病因素之一,低压状态可建立鼾症的动物模型。