新西兰兔慢性肾功能衰竭合并动静脉内瘘模型的建立

Animal model of arteriovenous fistula combined with chronic renal failure in New Zealand white rabbits

目的:建立慢性肾功能衰竭(chronic renal failure,CRF)合并颈部动静脉内瘘(arteriovenous fistula,AVF)的新西兰兔模型,研究CRF对AVF静脉内膜增生(venous neointimal hyperplasia,VNH)的影响。方法:32只健康新西兰兔随机等分为肾衰组和健康组,每组16只。肾衰组以腺嘌呤诱导新西兰兔CRF后建立AVF模型,健康组不做CRF诱导建立AVF模型。术后第4周取瘘口静脉段行HE染色评估内膜厚度、面积,免疫组织化学检测增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)的表达评估其增殖活性,取肾组织行HE染色观察病理学改变。结果:肾衰组血尿素氮、肌酐水平于第4周明显增加,第6周时达正常值3倍左右,光镜下可见肾小管萎缩消失、结晶物沉着、间质纤维化伴炎症细胞浸润;肾衰组AVF静脉平均内膜厚度、面积及PCNA表达量均明显高于健康组(P﹤0.05)。结论:腺嘌呤可诱导家兔CRF形成,CRF对VNH具有促进作用,加快AVF的功能障碍,因此在研究AVF早期功能障碍时需建立CRF的AVF模型,以保证研究的科学性。

Objective:To establish a rabbit model of chronic renal failure(CRF)combined with arteriovenous fistula(AVF),and to investigate the effect of CRF on venous neointimal hyperplasia(VNH)of AVF. Methods:Thirty-two healthy rabbits were randomly divided into renal failure group and health group(16 in each group). Rabbits in renal failure group were fed chow containing adenine.After induction of CRF,an AVF model in neck was established in renal failure group. Whereas,the same AVF model with no intervention was established in health group. Four weeks after operation,the pathological changes of fistula tissue,specifically the thickness and area of intimal in venous segment was observed by HE staining;the proliferation activity of the neointimal cells was evaluated by immunohistochemical staining of proliferating cell nuclear antigen(PCNA);the pathological changes of renal tissue was observed by HE staining. Results:Compared with those in health group,the levels of SCr and BUN in the renal failure group were increased significantly in the first four weeks,and were three times higher than baseline at the sixth weeks. HE staining of renal tissue in renal failure group showed amounts of crystals deposition within the tubules with partial atrophy,and the renal interstitium infiltrated with inflammatory cells and fibrosis. Compared with those of health group,the average thickness and area of VNH and PCNA-positive cells in venous segment were increased significantly in the renal failure group(P<0.05). Conclusion:The CRF rabbit model is successfully established by feeding adnine,which promotes the VNH and AVF dysfunction. Therefore,AVF combined with CRF model should be established for the early AVF dysfunction studies in the further.