腺嘌呤诱导的肾衰竭大鼠腹主动脉腔静脉内瘘模型的构建
Establishment of abdominal aortocaval fistula in adenine-induced renal failure rats
张艺斐 1梁黎明 2孔祥雷 2许姝琦 1王群 1王尊松 2许冬梅2
作者信息
- 1. 山东第一医科大学(山东省医学科学院),济南 250000;山东第一医科大学第一附属医院(山东省千佛山医院)肾病学科,济南 250014
- 2. 山东第一医科大学第一附属医院(山东省千佛山医院)肾病学科,济南 250014;山东省肾病研究所,济南 250014
- 折叠
摘要
目的 探索通过腺嘌呤诱导的肾衰竭大鼠构建腹主动脉腔静脉内瘘(abdominal aortocavalfistula,ACF)模型,为后续机制及干预研究提供合适的动物模型.方法 选择成年雌性Sprague-Dawley大鼠(250～300 g),按6∶1比例采用区组随机分组法随机分为肾衰竭组(n=60,0.75％腺嘌呤饲料)和对照组(n=10,不含腺嘌呤的相同饲料),喂饲4周后,肾衰竭组按1∶1比例采用区组随机分组法选取30只行开腹手术构建ACF模型(肾衰竭+ACF组).通过血肌酐及血尿素氮检测及Masson染色评估肾衰竭模型的建立,应用小动物超声成像系统验证ACF模型的构建情况.ACF手术6周后取材,心脏采血法取血并留取ACF大鼠血管组织进行病理学(HE染色)研究.结果 喂饲4周时,与对照组(n=10)比较,肾衰竭组(n=10)大鼠血肌酐[(63.8±23.5)μmol/L比(33.0±3.8)μmol/L,Z=3.651,P＜0.001]和血尿素氮[(13.1±6.9)mmol/L 比(5.3±0.6)mmol/L,Z=3.254,P=0.001]水平均较高.Masson染色结果显示肾衰竭组肾小管间质炎性细胞浸润、肾小管上皮细胞萎缩、间质纤维化及血管损伤等病理改变.ACF术后5只大鼠死亡,存活率为83.3％.多普勒超声结果显示,肾衰竭+ACF组通畅(23/25)的ACF吻合口处探及动脉向静脉分流的湍流血流.HE染色结果显示,肾衰竭+ACF组ACF静脉流出道出现典型的偏心性新生内膜增生.结论 腺嘌呤诱导的肾衰竭大鼠ACF模型构建成功,ACF表现典型的偏心性新生内膜增生,该模型可为自体动静脉内瘘新生内膜增生的机制研究及干预研究提供可靠的动物模型.
Abstract
Objective To explore the construction of abdominal aortocaval fistula(ACF)model in adenine-induced renal failure rats,and to provide a suitable animal model for subsequent mechanism and intervention researches.Methods Adult female Sprague-Dawley rats(250-300 g)were fed with 0.75％adenine diet(renal failure group,n=60)and the same diet without adenine(control group,n=10)for 4 weeks,and the rats were randomly grouped by block randomization method with a ratio of 6∶1.Thirty rats in the renal failure group were randomly selected by block randomization method at a ratio of 1∶1 to undergo laparotomies to establish ACF models(renal failure+ACF group).The serum creatinine,blood urea nitrogen detection and Masson staining were used to evaluate the establishment of renal failure model.Small animal ultrasound imaging system was applied to verify the successful construction of the ACF model.After 6 weeks of ACF observation,blood samples were collected from the heart of rats,and ACF-vascular tissues were collected for pathological study(HE staining).Results At 4 weeks of feeding,compared with the control group,serum creatinine[(63.8±23.5)μmol/L vs.(33.0±3.8)μmol/L,Z=3.651,P＜0.001]and blood urea nitrogen[(13.1±6.9)mmol/L vs.(5.3±0.6)mmol/L,Z=3.254,P=0.001]in the renal failure group were both higher.Masson staining showed renal tubulointerstitial inflammatory cell infiltration,renal tubular epithelial cell atrophy,interstitial fibrosis and vascular injury.Five rats sacrificed after ACF surgeries,and the survival rate was 83.3％.Doppler ultrasound showed turbulent blood flow of arterial to venous shunt at the anastomosis of open ACF(23/25)in the renal failure+ACF group.HE staining showed typical eccentric neointimal hyperplasia in the outflow tract of ACF vein in the renal failure+ACF group.Conclusions The adenine-induced ACF rat model is successfully constructed,and ACF shows typical eccentric neointimal hyperplasia.The ACF construction would provide a reliable animal model to study the mechanism and intervention of neointimal hyperplasia for autologous arteriovenous fistula.
关键词
腺嘌呤/肾功能不全/大鼠,Sprague-Dawley/腹主动脉腔静脉内瘘/静脉内膜增生Key words
Adenine/Renal insufficiency/Rats,Sprague-Dawley/Abdominal aortocaval fistula/Neointimal hyperplasia引用本文复制引用
基金项目
国家自然科学基金青年基金(82000728)
中国初级卫生保健基金会面上项目(HT202112220001)
齐鲁卫生与健康杰出青年人才项目(A001358)
山东第一医科大学青年科学基金培育资助计划(202201-082)
出版年
2024
NETL
NSTL
万方数据