肝衰竭动物模型的制备及其现状

生物人工肝是一种新型体外人工肝支持系统，它以培养肝细胞为材料，旨在充分代替肝脏的生物功能，为急性肝功能衰竭(ALF)患者提供可靠的过渡支持治疗。各种类型的生物人工肝研究都离不开体外肝支持的动物实验，合适的动物模型是其性能评价和进一步临床应用的重要条件。     

急性肝衰竭动物模型及人工肝支持系统动物实验

在过去的40年中,对于急性肝衰的认识和治疗发展很快,从而使病死率有所下降。通过研究能够反映人类临床、生化和病史特征的动物模型对这个疾病的认识有了很大的进展。而急性肝衰竭通过体外人工肝支持系统治疗也越来越受到重视。这篇综述评价了手术和药物等各种建立急性肝衰动物模型的方法,简要介绍其在生物型人工肝支持系统研究中的应用。     

急性肝衰竭动物模型及人工肝支持系统动物实验

在过去的40年中，对于急性肝衰的认识和治疗发展很快，从而使病死率有所下降。通过研究能够反映人类临床、生化和病史特征的动物模型对这个疾病的认识有了很大的进展。而急性肝衰竭通过体外人工肝支持系统治疗也越来越受到重视。这篇综述评价了手术和药物等各种建立急性肝衰动物模型的方法，简要介绍其在生物型人工肝支持系统研究中的应用。     

急性缺血性肝衰犬模型的制作

肝衰模型的制作有很多种方法。包括手术和药物诱导等方法。我们建立了一种生存期合适。制作周期不长的模型。     

人工肝干预肝衰竭凝血项变化的研究

急性肝衰竭是一种复杂的多系统疾病,短期内可迅速出现凝血功能障碍和肝性脑病 等并发症,凝血功能障碍严重者可导致大量出血,是肝功能衰竭患者死亡的主要原因。目前急性肝衰竭 的治疗主要包括内科综合治疗、人工肝支持系统、肝移植三种方法。本文就人工肝支持系统治疗对肝功 能衰竭患者凝血项变化的影响做一综述。     

第五届国际暨全国肝衰竭与人工肝学术会议纪要

2009年1月20-22日,由中华医学会感染病学分会肝衰竭与人工肝学组、中国生物医学工程学会人工器官分会和中华临床感染病杂志主办的第五届国际暨全国肝衰竭与人工肝学术会议于在历史悠久的榕城福州顺利召开。本次大会为期3天,共收到论文149篇,其中专题报告25篇,有来自我国及美国、俄罗斯、澳大利亚、日本和印度尼西亚等国家的600余名相关专家和学者到会作了专题报告并进行了学术交流。     

体外生物人工肝系统对暴发性肝衰竭兔的支持作用

目的探讨培养肝细胞用于生物人工肝及其作为肝移植辅助支持手段的可能性。方法以培养人肝细胞和中空纤维反应器为主要材料构成体外生物人工肝系统,对Ｄ-氨基半乳糖诱导的暴发性肝衰竭（ＦＨＦ）免进行人工肝支持实验。结果尽管两组实验动物的存活时间没有明显差异,但支持治疗组兔的血清转氨酶、总胆红素和肌酐水平均低于对照组,肝组织病理检查见肝细胞坏死程度明显轻于对照组,实验所用肝细胞保持较好的活力和贴壁能力。结论所用体外生物人工肝支持系统已发挥出培养肝细胞的生物作用,能够部分代偿ＦＨＦ兔的肝脏功能。【关键词】##4人工肝;;支持;;暴发性肝衰竭;;兔     

犬缺血性暴发肝衰模型的制备

为了给生物人工肝治疗暴发肝衰（ＦＨＦ）的实验研究提供可靠稳定的动物模型，我们采用一期肝周韧带离断，膈动脉缝扎，端侧门腔分流，肝动脉和胃十二指肠动脉结扎（即一期入肝血流完全阻断）法成功地制备了稳定的犬急性缺血性ＦＨＦ模型，现报道如下。一、材料与方法１．...     

兔慢性肝损害急性肝衰竭动物模型的建立

Objective To establish an ideal animal model of acute-on-chronic liver failure (ACLF) in New Zealand white rabbits in order to provide a large animal model for further researches.Methods Totally 75 New Zealand rabbits were randomly divided into experimental group (n =70) and control group (n = 5 ). Rabbits in the experimental group were injected with CCl4 into the abdominal cavity twice every week and the doses of CCl4 were modified according to the index of liver function and the body weight, whereas those in the control group were treated with the same volume of saline. At the 10th week,48 New Zealand rabbits with hepatic fibrosis were randomly assigned to 4 groups and injected with CCl4 as before, D-Gal at a dose of 0. 65 g/kg body weight (BW), 0. 70 g/kg BW and 0. 75 g/kg BW, respectively. By observing and comparing the general state, survival time, biochemical indexes, and the histopathology, a method of establishing a stable animal model of acute hepatic failure was found. Results As compared with those in control group, the levels of ALT, AST, GGT, HA, LN and PC-Ⅲ in the experiment group were increased significantly, while the level of ALB was decreased at the end of 10 weeks. Typical features of hepatic fibrosis and the formation of pseudo-lobules were observed at the end of 10 weeks. After treatment with D-Gal, all rabbits in group Ⅰ survived with minimal changes in liver function tests. In group Ⅱ , there was a temporary hepatic injury, but no hepatic coma. Four of the 12 rabbits died (33. 3% ). In group Ⅲ , biochemical indexes changed obviously 12 h after the administration and hepatic injury reached its peak after 48 h. Ten of 12 rabbits were died of severe hepatic failure with a survival time of ( 53. 00 ± 25. 69) h. Histology of liver section revealed massive necrosis in nodules. In group Ⅳ , hepatic injury occurred early and severely. All the rabbits died of severe hepatic failure with a survival time of (32. 70 ± 17. 46) h. Conclusion The experimental model of ACLF could be established by injected with D-Gal in New Zealand rabbits with hepatic fibrosis, induced by CCl4 intraperitoneal injection for 10 weeks.The one induced by 0. 70 g/kg of D-galactosamine was more stable and showed similar clinical pathophysiological changes in human beings. So it can be a good experimental platform for studies of ACLF.     

兔慢性肝损害急性肝衰竭动物模型的建立

Objective To establish an ideal animal model of acute-on-chronic liver failure (ACLF) in New Zealand white rabbits in order to provide a large animal model for further researches.Methods Totally 75 New Zealand rabbits were randomly divided into experimental group (n =70) and control group (n = 5 ). Rabbits in the experimental group were injected with CCl4 into the abdominal cavity twice every week and the doses of CCl4 were modified according to the index of liver function and the body weight, whereas those in the control group were treated with the same volume of saline. At the 10th week,48 New Zealand rabbits with hepatic fibrosis were randomly assigned to 4 groups and injected with CCl4 as before, D-Gal at a dose of 0. 65 g/kg body weight (BW), 0. 70 g/kg BW and 0. 75 g/kg BW, respectively. By observing and comparing the general state, survival time, biochemical indexes, and the histopathology, a method of establishing a stable animal model of acute hepatic failure was found. Results As compared with those in control group, the levels of ALT, AST, GGT, HA, LN and PC-Ⅲ in the experiment group were increased significantly, while the level of ALB was decreased at the end of 10 weeks. Typical features of hepatic fibrosis and the formation of pseudo-lobules were observed at the end of 10 weeks. After treatment with D-Gal, all rabbits in group Ⅰ survived with minimal changes in liver function tests. In group Ⅱ , there was a temporary hepatic injury, but no hepatic coma. Four of the 12 rabbits died (33. 3% ). In group Ⅲ , biochemical indexes changed obviously 12 h after the administration and hepatic injury reached its peak after 48 h. Ten of 12 rabbits were died of severe hepatic failure with a survival time of ( 53. 00 ± 25. 69) h. Histology of liver section revealed massive necrosis in nodules. In group Ⅳ , hepatic injury occurred early and severely. All the rabbits died of severe hepatic failure with a survival time of (32. 70 ± 17. 46) h. Conclusion The experimental model of ACLF could be established by injected with D-Gal in New Zealand rabbits with hepatic fibrosis, induced by CCl4 intraperitoneal injection for 10 weeks.The one induced by 0. 70 g/kg of D-galactosamine was more stable and showed similar clinical pathophysiological changes in human beings. So it can be a good experimental platform for studies of ACLF.     

兔慢性肝损害急性肝衰竭动物模型的建立

目的 建立新西兰兔的慢加急性肝衰竭(ACLF)动物模型.方法 将75只新西兰兔随机分为实验组(n=70)与对照组(n=5),实验组采用四氯化碳(CCl4)腹腔注射建立兔代偿性肝纤维化模型,每周2次,通过体质量及谷丙转氨酶(ALT)/谷草转氨酶(AST)改变调整药物剂量,共10周,获得48只肝纤维化新西兰兔,在此基础上将动物随机分为4组(n=12),Ⅰ组:继续腹腔注射CCl4,Ⅱ组:静脉注射D-氨基半乳糖(D-Gal)0.65 g/kg,Ⅲ组:静脉注射D-Gal 0.70 g/kg,Ⅳ组:静脉注射D-氨基半乳糖0.75 g/kg,观察各组动物的一般情况、生化指标及病理改变.结果 与对照组比较,肝纤维化实验组兔10周时ALT、AST、ALB、γ-谷氨酰转肽酶(GGT)、透明质酸(HA)、层粘连蛋白(LN)、Ⅲ型前胶原(PC-Ⅲ)差异均有统计学意义(P＜0.05),可观察到肝纤维化的病理表现,出现典型的假小叶,在肝纤维化基础给予D-Gal后,Ⅰ组动物全部存活,生化指标轻度改变;Ⅱ组动物死亡率为33.3%(4/12),生化指标仅出现一过性的改变;Ⅲ组动物死亡率为83.3%(10/12),平均存活时间为(53.00±25.69)h,给药后12 h生化指标及临床表现出现改变,48 h达到高峰,病理显示肝脏大块坏死;Ⅳ组动物均死于肝衰竭,平均存活时间为(32.70±17.46)h,肝损害出现时间早,损伤剧烈.结论 对CCl4诱导的肝纤维化新西兰兔给予D-Gal急性攻击可建立ACLF模型.其中给予D-Gal 0.70 g/kg的模型稳定性好,能较大程度上的模拟临床上ACLF的病理生理过程.

Abstract：

Objective To establish an ideal animal model of acute-on-chronic liver failure (ACLF) in New Zealand white rabbits in order to provide a large animal model for further researches.Methods Totally 75 New Zealand rabbits were randomly divided into experimental group (n =70) and control group (n = 5 ). Rabbits in the experimental group were injected with CCl4 into the abdominal cavity twice every week and the doses of CCl4 were modified according to the index of liver function and the body weight, whereas those in the control group were treated with the same volume of saline. At the 10th week,48 New Zealand rabbits with hepatic fibrosis were randomly assigned to 4 groups and injected with CCl4 as before, D-Gal at a dose of 0. 65 g/kg body weight (BW), 0. 70 g/kg BW and 0. 75 g/kg BW, respectively. By observing and comparing the general state, survival time, biochemical indexes, and the histopathology, a method of establishing a stable animal model of acute hepatic failure was found. Results As compared with those in control group, the levels of ALT, AST, GGT, HA, LN and PC-Ⅲ in the experiment group were increased significantly, while the level of ALB was decreased at the end of 10 weeks. Typical features of hepatic fibrosis and the formation of pseudo-lobules were observed at the end of 10 weeks. After treatment with D-Gal, all rabbits in group Ⅰ survived with minimal changes in liver function tests. In group Ⅱ , there was a temporary hepatic injury, but no hepatic coma. Four of the 12 rabbits died (33. 3% ). In group Ⅲ , biochemical indexes changed obviously 12 h after the administration and hepatic injury reached its peak after 48 h. Ten of 12 rabbits were died of severe hepatic failure with a survival time of ( 53. 00 ± 25. 69) h. Histology of liver section revealed massive necrosis in nodules. In group Ⅳ , hepatic injury occurred early and severely. All the rabbits died of severe hepatic failure with a survival time of (32. 70 ± 17. 46) h. Conclusion The experimental model of ACLF could be established by injected with D-Gal in New Zealand rabbits with hepatic fibrosis, induced by CCl4 intraperitoneal injection for 10 weeks.The one induced by 0. 70 g/kg of D-galactosamine was more stable and showed similar clinical pathophysiological changes in human beings. So it can be a good experimental platform for studies of ACLF.     

Animal models of craniosynostosis

BackgroundVarious animal models mimicking craniosynostosis have been developed, using mutant zebrafish and mouse. The aim of this paper is to review the different animal models for syndromic craniosynostosis and analyze what insights they have provided in our understanding of the pathophysiology of these conditions.Material and methodsThe relevant literature for animal models of craniosynostosis was reviewed.ResultsAlthough few studies on craniosynostosis using zebrafish were published, this model appears useful in studying the suture formation mechanisms conserved across vertebrates. Conversely, several mouse models have been generated for the most common syndromic craniosynostoses, associated with mutations in FGFR1, FGFR2, FGFR3 and TWIST genes and also in MSX2, EFFNA, GLI3, FREM1, FGF3/4 genes. The mouse models have also been used to test pharmacological treatments to restore craniofacial growth.ConclusionsSeveral zebrafish and mouse models have been developed in recent decades. These animal models have been helpful for our understanding of normal and pathological craniofacial growth. Mouse models mimicking craniosynostoses can be easily used for the screening of drugs as therapeutic candidates.     

Animal models of scoliosis

Multiple techniques designed to induce scoliotic deformity have been applied across many animal species. We have undertaken a review of the literature regarding experimental models of scoliosis in animals to discuss their utility in comprehending disease aetiology and treatment. Models of scoliosis in animals can be broadly divided into quadrupedal and bipedal experiments. Quadrupedal models, in the absence of axial gravitation force, depend upon development of a mechanical asymmetry along the spine to initiate a scoliotic deformity. Bipedal models more accurately mimic human posture and consequently are subject to similar forces due to gravity, which have been long appreciated to be a contributing factor to the development of scoliosis. Many effective models of scoliosis in smaller animals have not been successfully translated to primates and humans. Though these models may not clarify the aetiology of human scoliosis, by providing a reliable and reproducible deformity in the spine they are a useful means with which to test interventions designed to correct and prevent deformity. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:458–467, 2015.