Comparison of renal damage by iodinated contrast or gadolinium in an acute renal failure rat model based on serum creatinine levels and apoptosis degree

This study was undertaken to compare renal damage, as determined by serum creatinine and degree of apoptosis, caused by iodinated contrast or gadolinium in an acute renal failure (ARF) rat model. Rats were divided into three groups; controls (n=3), a CT contrast medium group (n=9), and an MR contrast medium group (n=9). The CT and MR groups were further subdivided into three groups, namely, low, standard, and high dose subgroups. Renal function was evaluated by determining serum creatinine levels; before ARF, and 48 hr after ARF and contrast administration. Apoptosis was assayed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). No significant creatinine level differences were observed between the CT and MR groups (p=0.116). Degrees of apoptosis in the renal cortex and medulla were more severe in the CT contrast medium group than in the control or MR contrast medium group (p<0.05). The study shows that CT contrast medium did not aggravate renal function more so than MR contrast medium in this ARF rat model. However, apoptosis examination in the renal cortex and medulla indicated that CT contrast medium induced more severe apoptosis than MR contrast medium (p<0.05). We conclude that CT contrast medium can be used for renal imaging studies when subjects are well hydrated and preventive medication is administered.     

Prolonged reversible acute renal failure in focal glomerulonephritis with severe nephrotic syndrome in an elderly patient

Summary A clinical report of a 67-year-old woman who developed reversible acute renal failure due to focal glomerulonephritis with severe nephrotic syndrome is presented. The patient required four weeks' dialysis treatment but recovered completely. The role of temporary dialysis and diuretics on the clinical course and the reversibility of the process in old age is discussed.Abbreviations ARF Acute Renal Failure - Ccr Creatinine clearance - FGN Focal Glomerulonephritis - G.N. Glomerulonephritis - MCD Minimal change disease - N.S. Nephrotic syndrome     

Exploring an animal model of amodiaquine-induced liver injury in rats and mice

Amodiaquine (AQ) is associated with a relatively high incidence of idiosyncratic drug-induced liver injury (IDILI) and agranulocytosis. A previous study reported that a combination of high dose AQ and glutathione (GSH) depletion led to liver injury. However, the characteristics of this toxicity were very different from AQ-induced liver injury in humans. We developed a model of AQ-induced liver injury with characteristics similar to the injury in humans by treating mice with lower doses of AQ for several weeks. In this study we found that not only did GSH depletion not increase AQ covalent binding to hepatic proteins at this lower dose, but also it paradoxically prevented the liver injury. We extended the model to rats and found AQ treatment led to a mild delayed onset liver injury that resolved despite continued treatment with AQ. Immunohistochemistry indicated the presence of Kupffer cell activation, apoptosis and hepatocyte proliferation in the liver. There was also an increase in serum IL-2, IL-5, IL-9, IL-12, MCP-1 and TGFβ, but a decrease in leptin. Coincident with the elevated serum ALT, the number of liver CD4⁺ T-cells, IL-17 secreting cells and T_H17/T_reg cells increased at Week 3 and decreased during continued treatment. Increases in NK1.1+ cells and activated M2 macrophages were also observed during liver injury. These results suggest that the outcome of the liver injury was determined by the balance between effector and regulatory cells. Co-treatment with cyclosporin prevented AQ-induced liver injury, which supports an immune mechanism. Retinoic acid (RA), which has been reported to enhance natural killer (NK) cell activity, exacerbated AQ-induced liver injury. These results suggest that AQ-induced IDILI is immune mediated and the subsequent adaptation appears to represent immune tolerance.     

Computer analysis system of blood oxygen saturation in an animal hypoxia model

An experimental animal hypoxia model has been developed. It consists of two sensors (an in vitro and in vivo model), an experimental device and a computer signal processing system. This method can easily be applied to determine and analyse blood oxygen saturation at various hypoxia levels. It can also be used to evaluate the accuracy of pulse oximetry over a wide range of oxyhemoglobin desaturation levels. The DC and AC components of recorded red and infra-red signals, the dual-wavelength ratio R₁₂ and the reading of a pulse oximeter (SpO₂) can be automatically calculated and displayed on a computer screen. Preliminary results of the animal hypoxia test indicate that the measurements made by the instrument correlate well with the oxygen saturation readings of the automatic blood gas analyser AVL945. The computer analysis system is suitable for repeated estimations in the animal model.     

短暂肾缺血建立急性肾功能衰竭动物模型

目的:建立更加符合临床实际的以肾血流减少为特征的急性肾功能衰竭(ARF)动物模型。方法:家兔双侧肾动脉不完全结扎造成肾缺血,20 min后恢复肾血流。检测动物在肾动脉不完全结扎前、后及恢复血流后的尿量、血清肌酐、电解质、血气分析并做肾脏病理学检查。结果:肾血流减少后,动物尿量明显减少,而血清肌酐水平显著升高;同期血清钾水平升高,pH降低,HCO3-及BE明显减少。恢复肾血流后尿量增多并逐步趋向正常;至恢复血流1 h时血清肌酐水平已降至正常,但代谢性酸中毒持续发展,血清钾水平降低后又有所回升。缺血20 min及恢复血流1 h和5 h的兔肾病理检查无明显改变。结论:双侧肾动脉不完全结扎法复制出的动物模型具有ARF的多重表现和功能性ARF的特点,体现了肾血流因素在ARF发生及治疗方面的临床意义,可供教学和科研参考。     

C-反应蛋白诱导人肾小管上皮细胞凋亡

目的:探讨与微炎症状态相应的C-反应蛋白(CRP)水平是否诱导肾小管上皮细胞凋亡。方法:以微炎症状态相应的CRP浓度刺激HK-2细胞。采用AnnexinⅤ-FITC、PI染色和流式细胞术检测凋亡细胞的百分率。采用Hoechst 33258染色观察肾小管上皮细胞凋亡的形态学改变。比色法检测细胞caspase-3活性。Real-time PCR检测促凋亡基因bax、抗凋亡基因bcl-2的mRNA表达。结果:CRP呈剂量和时间依赖性地诱导HK-2细胞凋亡,细胞凋亡在CRP浓度为10 mg/L时达高峰,在20 mg/L时则以晚期凋亡和坏死为主。Hoechst 33258细胞核染色显示CRP作用的HK-2细胞呈现染色质浓缩、碎裂或染色质边集等细胞凋亡的特点。CRP增高细胞caspase-3的酶活性、上调促凋亡基因bax的表达和下调抗凋亡基因bcl-2的表达。结论:CRP轻度增高可诱导肾小管上皮细胞凋亡。     

中国株庚型肝炎病毒(HGV)感染猕猴的实验研究

应用０．５ｍｌ含中国株庚型肝炎病毒（ＨＧＶ）的血清接种５只猕猴，５只猕猴于接种后１周血清ＨＧＶＲＮＡ均阳转；ＨＧＶＲＮＡ滴度在猴体内可高达１∶１０５，较接种血清中ＨＧＶＲＮＡ滴度（１∶１０２）高出许多，提示ＨＧＶ在猕猴体内复制。其中４只猕猴血清抗－ＨＧＶ阳转；４只出现ＡＬＴ异常。后用其中１只猕猴感染后４５天的血清给另２只猕猴接种，该２只猴也出现血清ＨＧＶＲＮＡ和抗－ＨＧＶ阳转及ＡＬＴ异常。本研究表明，中国猕猴有可能作为ＨＧＶ感染的动物模型。     

供体取双肾的大鼠肾移植模型手术方法和技巧

目的探索一种新的大鼠取肾方法,建立稳定的供体取双肾的大鼠肾移植模型。方法30只180～220gF344大鼠,雌雄各半,随机选取10只做为供体,用一种新的方法摘取双肾,分别对20只受体做左侧原位肾移植,动脉采用供体带盘和受体腹主动脉端侧吻合,静脉采用端端吻合,供体输尿管膀胱瓣和受体膀胱吻合重建尿路,术后第二天背侧右肋肌角入路切除受体右侧健肾,观察大鼠成活天数。结果受体除1例因血尿路梗阻切除健肾后第2天死亡,其余受体均成活超过3个月,手术成功率95%。结论大鼠肾移植模型中,采用新的取肾方法,供体的双肾均能成功加以利用,手术时间和热缺血时间短,受体手术成功率高。     

炎症性肠病动物模型的研究概况

The etiology and pathogenesis of inflammatory bowel disease are up to now still not clear and definite. Establishing the ideal animal model to study its cause and pathogenesis of this disease is very important. The ideal animal model should have the same manifestation with human inflammatory bowel disease on clinical and pathologic feature etc. In this article, the method, the pathologic character isfics and concerning pathogenesis, of a few common useful experiment animal models are discussed.     

Stress vulnerabilities in an animal model of post-traumatic stress disorder

We have studied the effects of inescapable electric foot shocks (ISs) on rats by using a subsequent avoidance/escape task performed in a shuttle box as an animal model of post-traumatic stress disorder (PTSD). In this study, the behavioral differences and the effects of chronic stress exposure prior to IS were examined among male rats of the Wistar, Fischer 344, and Lewis strains. In concordance with our previous report on the Wistar rats, we observed the characteristic features of PTSD in all three rat strains tested, that is, the hyperactive and hypoactive bidirectional behavioral changes that are associated with hypervigilant and hyperarousal behavior, and the numbing and avoidant behavior, respectively. The induction of hypoactive behaviors after IS was most exaggerated in the Fischer and Lewis strains. Although the count of hyperactive behaviors was maximal in the Fischer strain both at basal levels without IS and after IS, the increase in the rate of hyperactive behaviors by IS was the most prominent in the Lewis strain. In addition, preloaded chronic variable stress (CVS) enhanced the degree of hyperactive behavioral changes in the Wistar strain. Thus, we consider that the present study further validates the use of shuttle box paradigm as an animal model of PTSD by demonstrating the vulnerability due to genetic background and environmental preloaded stress.     

大鼠生殖道炎症动物模型的构建

目的:构建苯酚胶浆致大鼠阴道及宫颈炎动物模型。方法:切除双侧大白鼠卵巢,注射苯甲酸雌二醇和氢化可的松,造成假动情期和全身免疫功能低下,然后每鼠阴道内注入苯酚胶浆0.1 ml,隔天一次共3次,每天观察并记录外阴变化,术后第15 d称重后眼球取血以显微镜计数法测定白细胞总数,断颈处死取阴道及宫颈进行病理学检查。结果:大鼠阴道口红肿、有的有脓性物流出;宫颈肥大,阴道及宫颈黏膜上皮细胞变性坏死或脱落,形成溃疡,膜下有充血水肿、炎细胞浸润、腔内有大量炎性或脓性渗出物及坏死组织;腺体有不同程度增生及鳞状化生;白细胞总数明显增高;体重减轻。结论:成功构建了阴道宫颈炎大鼠动物模型,为进一步研究HMGN家族等分子在调控女性生殖道炎症发生发展的机制研究打下了基础。     

原发性肝泡球蚴动物模型的建立

目的 模拟包虫病自然感染途径,建立原发性肝泡球蚴（Ｅｃｈｉｎｏｃｏｃｃｕｓ ｍｕｌｔｉｌｏｃｕｌａｒｉｓ,Ｅ．ｍ）动物模型。方法 采用开腹直视下肝穿刺注射,直穿刺注射和门静脉系侧支血管穿刺注射．Ｅ．ｍ组织混悬液的方法,制备原发性肝Ｅ．ｍ泡球蚴动物模型,并以腹腔穿刺接种制备继发性动物模型作为对照。     

开放爆炸环境下烧冲复合伤动物模型建立的研究

目的：建立理想的开放爆炸环境下烧冲复合伤动物模型。方法以Wistar雌性清洁级成年大鼠460只为研究对象。随机选取90只大鼠设为预实验组,其余370只大鼠随机选取360只大鼠设为实验组,剩余10只大鼠设为正常对照组。预实验组90只大鼠随机分为预单纯烧伤组（n=30）,预烧冲复合伤组（n=30）,预烧冲复合伤组（n=30）;预单纯烧伤组采用凝固汽油涂抹背部点燃25 s造成深Ⅱ度烧伤,烧伤面积分别为10％总体表面积（TBSA）（轻度,n=10）、25％TBSA（中度,n=10）、40％TBSA（重度,n=10）;预单纯冲击伤组采用柱形黑索金炸药在不同距离（70、50、30 cm）造成轻度、中度、重度冲击伤（每组n=10）;按照预单纯烧伤组及预单纯冲击伤组动物死亡率及器官功能障碍等,确定轻度、中度、重度的预烧冲复合伤模型：预轻度烧冲复合伤（轻度烧伤＋轻度冲击伤）,预中度烧冲复合伤（中度烧伤＋中度冲击伤）,预重度烧冲复合伤（重度烧伤＋重度冲击伤）;观察伤后24 h大鼠宏观变化及死亡率。实验组370只大鼠随机分为单纯烧伤组（n=120,其中轻、中、重3组,每组n=40）,单纯冲击伤组（n=120,其中轻、中、重3组,每组n=40）,烧冲复合伤组（n=120,其中轻、中、重3组,每组n=40）,正常对照组（n=10）,模型的建立同预实验,伤后6 h、1 d、2 d、3 d用自动生化仪检测实验组大鼠血清肌酸激酶同工酶（CK-MB）、谷丙转氨酶（GPT）、血肌酐（Scr）,并同时观察实验组大鼠死亡率及用光学显微镜观察各脏器病理变化。结果预轻、中、重度冲击伤组大鼠伤后24 h死亡率分别为10％、30％、100％;预轻、中、重度烧伤组大鼠伤后24 h死亡率分别为10％、20％、40％;预轻、中、重度烧冲复合伤组大鼠伤后24 h死亡率分别为20％、30％、100％;预冲击伤组：预重度冲击伤组大鼠     

Zebrafish as a new animal model to study lymphangiogenesis

The lymphatic system is essential for fluid homeostasis, fat absorption and immune responses, and also plays key roles under pathological conditions, such as tumor metastasis, lymphoedema and inflammation. The main function of the lymphatic vascular system is to return excess interstitial fluid back to the blood vascular system. Lymph, including fluid, macromolecules, leukocytes and activated antigen-presenting cells, is transported from the blind-ended lymphatic capillaries toward the collecting lymphatic vessels; for there, it is returned to the blood circulation through lymphatico-venous junctions (Alitalo et al. in Nature 438:946–954, 2005). Despite its importance, lymphangiogenesis remains poorly understood. The lack of specific markers has complicated the identification of lymph vessels, and a small animal model that could be genetically manipulated to discover the function of novel lymphangiogenic candidates has only recently become available (Ny et al. in Nat Med 11(9):998–1004, 2005). Since 2004, we have worked to make the zebrafish a new genetic model for unraveling the function of candidate genes involved in lymphangiogenesis. We have demonstrated that zebrafish possess a lymphatic vascular system that shares the morphological, molecular and functional characteristics of the lymphatic vessels found in other vertebrates (Yaniv et al. in Nat Med 12(6):711–716, 2006). In this process, we realized that it was necessary to seek a common definition for the lymph system which would be applicable from fish to man. The aim of this article is to review classical, mainly morphological, studies in order to elucidate the nature of the lymphatic system.     

周围神经缺血再灌注损伤动物模型的改良

目的研究周围神经缺血再灌注损伤动物模型的改良与建立。方法采用无损伤动脉夹暂时阻断大鼠一侧髂总动脉起始处血流,同时夹闭髂内、髂外动脉,一段时间后打开动脉夹,观察不同缺血再灌注时间下动物肢体功能情况,以及周围神经缺血导致的脊髓电镜下超微结构的改变,明确改良动物模型的实验效果。结果缺血时间的延长动物后肢的瘫痪症状逐渐加重。电镜观察脊髓神经元显示随再灌注时间的延长,神经元损害明显加重。结论用无损伤动脉夹阻断一侧髂总动脉和髂内、髂外动脉的周围神经缺血再灌注损伤的动物模型是对以往模型的改良。该模型制备操作简单,对动物的损伤更小,可得到理想的实验效果。     

实验性子宫内膜异位症动物模型研究

目的　利用大鼠子宫内膜异位症动物模型 ,探讨卵巢切除术和丹那唑治疗对大鼠子宫内膜异位症的影响。方法　将已成模大鼠随机分为 3组 :对照组 (n =2 3)、卵巢切除术组 (n =2 4)和丹那唑组 (n =2 9) ,在行双侧卵巢切除术或丹那唑治疗后的 2、4、6和 8周处死大鼠 ,同时观察移植物的生长情况。结果　卵巢切除术组和丹那唑组大鼠移植物体积均明显缩小 ,并且 4、6和 8周与 2周相比 ,作用更明显。组织学检查 ,对照组异位子宫内膜呈增生状态 ,而卵巢切除术组和丹那唑组呈萎缩状态。结论　卵巢切除术和丹那唑治疗可使大鼠异位子宫内膜逐渐萎缩退化 ,但未能使其消失 ,丹那唑的治疗作用具有时间相关性。     

奥美沙坦酯对慢性心力衰竭小鼠肾脏损伤的保护作用

目的: 探讨奥美沙坦酯对慢性心力衰竭小鼠肾脏损伤的影响。方法: 健康C57小鼠分为假手术组(sham组)、慢性心力衰竭组(CHF组)和奥美沙坦酯治疗组(OLM+CHF组)。以冠状动脉左前降支结扎法建立慢性心力衰竭小鼠模型,其中奥美沙坦酯治疗组以10 mg/kg剂量每天胃饲。12周时观察各组小鼠心率、血压、心功能状况、血肌酐、血尿素氮、血浆和肾脏血管紧张素Ⅱ水平;real-time PCR法检测肾脏肾素、血管紧张素1型受体(AT1R)和血管紧张素原(AGT)的表达情况,PAS染色观察肾组织结构变化。结果: 与shan组相比,CHF组和OLM+CHF组左室舒张末期内径(LVDd)和左室收缩末期内径(LVDs)显著增加(P＜0.05),短轴缩短率(FS)和射血分数(EF)显著降低(P＜0.05)。与sham组相比,CHF组收缩压、血肌酐和血尿素氮含量显著增高,OLM+CHF组以上指标较CHF组均显著降低(P＜0.05)。与sham组相比,CHF组血浆和肾脏血管紧张素Ⅱ水平增高,肾素、AT1R和AGT表达增高(P＜0.05),OLM+CHF组肾脏血管紧张素Ⅱ水平、肾素、AT1R和AGT表达较CHF组均显著降低(P＜0.05)。CHF组PAS染色可见肾小球系膜区扩张,肾小管间质PAS阳性染色物明显增多。OLM+CHF组肾小球系膜区和肾小管间质PAS染色阳性物质与CHF组相比明显减少。结论: 慢性心力衰竭可使肾内肾素血管紧张素系统激活并导致肾脏损伤,奥美沙坦酯通过抑制血管紧张素Ⅱ起到肾脏保护作用。     

急性脊髓损伤动物模型的建立与评估

BACKGROUND: There are a variety of methods for modeling spinal cord injury at home and abroad, showing their own advantages and disadvantages, but not yet a kind of objective and standardized model meeting the clinical research. OBJECTIVE:To design a simple impactor used for establishing the spinal cord injury model, then to evaluate the parameters and stability of the Allen’s spinal cord injury model through comparing with the New York University (NYU) impactor established model. METHODS: Female rats were equivalently allotted into five groups: sham-operation group (group A), self-made impactor 5 and 10 cm groups (group B1 and B2) and NYU 1.25 and 2.5 cm groups (group C1 and C2). All groups except group A were subjected to striking at different heights. Behavioral scores were detected at 1, 3, 5 and 7 days after modeling. Nissl staining was used to observe the morphological changes after freezing section and semiquantitative analysis. RESULTS AND CONCLUSION:(1) At the same time point, the behavioral scores, damaged area ratio of spinal cord and semiquantitative analysis of dorsal horn neurons showed significant differences in the group A compared with the other groups, also between groups B1 and B2, and groups C1 and C2 (P < 0.05), but no significant differences were found between groups B1 and C1, as well as groups B2 and C2 (P > 0.05). (2) In the group A, there was a clear boundary between the grey and white matter in a butterfly shape, numerous neurons with large nucleus and obvious nucleolus, and plaques or tabby of Nissl body appeared in the cytoplasm. In contrast, in the other four groups, there were few neurons, different degrees of Gore focal, swelling, demyelinating, and vacuole of cellula could be found, and Nissl body was fuzzy or disappeared. These results administrate that the self-made impactor can establish different damage degrees of spinal cord inury models, which are close to the NYU-made models. Moreover, it can be helpful for study on spinal cord injury for reasons of good stability, low cost, and operated easily. 中国组织工程研究杂志出版内容重点：肾移植;肝移植;移植;心脏移植;组织移植;皮肤移植;皮瓣移植;血管移植;器官移植;组织工程     

单侧输尿管梗阻大鼠模型中p38MAPK表达与细胞凋亡

目的： 探讨p38MAPK在大鼠单侧输尿管梗阻(UUO)模型肾组织中的表达及其在肾小管间质细胞凋亡和纤维化过程中可能发挥的作用。方法: 将25只Wistar大鼠中的18只行左侧输尿管结扎术，另外7只行假手术。分别于术后第3、7和14 d处死各组大鼠，行HE和Masson染色，观察肾脏病理变化；免疫组织化学方法测定增殖细胞核抗原（PCNA）表达；原位末端标记法（TUNEL）与DNA电泳观察肾小管间质细胞凋亡情况；Western blotting检测肾组织半胱氨酸天门冬氨酸蛋白酶-3（caspase-3）和p38丝裂素激活蛋白激酶（p38MAPK）及其磷酸化产物（p-p38MAPK）的表达。结果: 与假手术组比较，UUO模型组肾脏病理改变加重，TUNEL染色及DNA琼脂糖凝胶电泳可见大量的肾小管间质细胞凋亡，肾间质细胞PCNA表达明显增加，肾组织caspase-3的表达也显著增加（P<0.05）。p38MAPK蛋白水平在各组之间比较没有明显差别（P>0.05）。p-p38MAPK蛋白在正常肾脏有低水平表达，UUO模型组随着梗阻时间延长表达逐渐增多；第7 d达高峰，第14 d开始下降（P<0.05）。结论: p38MAPK信号通路可能参与了UUO致肾小管间质细胞凋亡和肾间质纤维化过程。     

siRNA targeting Survivin inhibits growth and induces apoptosis in human renal clear cell carcinoma 786-O cells

We investigated the inhibitory effect of small interfering RNA (siRNA) targeting Survivin gene on cell proliferation and apoptosis in human renal clear cell carcinoma 786-O cells. qRT-PCR, immunocytochemistry, and Western Blot were used to detect Survivin gene expression in 786-O cells. Cell proliferation was determined by BrdU assay and PCNA expression. Cell apoptosis was analyzed through detection of caspase-3 activity, and the effect of Survivin-siRNA on Bcl-2 gene expression was also examined. Forty-eight hours after transfection, Survivin expression was markedly inhibited at the mRNA and protein level. Downregulation of Survivin resulted in a significant inhibition of tumor cell growth. Caspase-3 activity showed that siRNA targeting Survivin gene induced cell apoptosis in 786-O cells. Moreover, Bcl-2 protein expression was markedly inhibited by transfection with siRNA against Survivin. These results indicate that siRNA targeting Survivin gene can downregulate Survivin gene expression in 786-O cells, inhibit growth, and induce apoptosis of renal carcinoma cells.