中国组织工程研究与临床康复
中國組織工程研究與臨床康複
중국조직공정연구여림상강복
JOURNAL OF CLINICAL REHABILITATIVE TISSUE ENGINEERING RESEARCH
2009年
53期
10495-10498
,共4页
徐繁%潘兴华%冯凡哲%李潇%杨仁华%李自安
徐繁%潘興華%馮凡哲%李瀟%楊仁華%李自安
서번%반흥화%풍범철%리소%양인화%리자안
局灶节段性肾小球硬化%肾切除%阿霉素%疾病模型%动物
跼竈節段性腎小毬硬化%腎切除%阿黴素%疾病模型%動物
국조절단성신소구경화%신절제%아매소%질병모형%동물
背景:单侧肾切除联合阿霉素诱导的大鼠肾小球硬化模型常用于抗肾小球硬化药物的筛选和评价,但目前很少有此方法诱导兔肾小球硬化模型的报道.目的:建立家兔肾小球硬化动物模型,并观察造模过程中动物的肾脏功能和组织病理学变化.设计、时间及地点:随机对照动物实验,于2008-12/2009-05在解放军成都军区昆明总医院实验动物中心完成.材料:日本大耳家兔25只,雌雄各半,体质量1.75～2.25 kg,用于建立家兔肾小球硬化动物模型,并随机分为正常组10只和模型组15只.方法:模型组30 g/L戊巴比妥钠生理盐水溶液(1 mL/kg)麻醉,开腹摘除左肾.正常组行假手术,不摘除肾脏,余与上同.手术1周后,模型组注射阿霉素5 mg/kg,2 周后注射阿霉素3 mg/kg.正常组同步注射生理盐水.主要观察指标:于实验前、造模后4,6,8周对两组兔进行肾功能相关血液生化指标检测,并留尿液测24 h尿蛋白量.于第2次注药后8周分别两组随机各取1只兔肾组织,进行病理观察.结果:①模型组肾脏略白,质地略韧,表面尚光滑.②模型组光镜下可见细胞外基质增生明显,系膜区扩张,肾球囊壁与肾小球毛细血管拌粘连,小管上皮变性甚至萎缩出现肾间质纤维化,间质炎细胞浸润,呈现弥漫性节段性肾小球硬化等病理特征.③与正常组家兔比较,模型组家兔总蛋白及白蛋白明显下降,三酰甘油、总胆固醇、低密度脂蛋白胆固醇、尿素氮、肌酐均显著升高,模型组家兔尿蛋白含量于实验第4周开始明显升高,在实验期间明显高于对照组,但在第8周逐渐趋向平台.④SPECT示:正常组肾小球总滤过率为92.6 mL/min,模型组为33 mL/min;可见模型组右侧肾脏肾小球滤过率明显下降.结论:单侧肾切除联合阿霉素导致家兔的肾小球硬化形成,并且肾功能及24 h尿蛋白定量有较明显的阶段性变化.
揹景:單側腎切除聯閤阿黴素誘導的大鼠腎小毬硬化模型常用于抗腎小毬硬化藥物的篩選和評價,但目前很少有此方法誘導兔腎小毬硬化模型的報道.目的:建立傢兔腎小毬硬化動物模型,併觀察造模過程中動物的腎髒功能和組織病理學變化.設計、時間及地點:隨機對照動物實驗,于2008-12/2009-05在解放軍成都軍區昆明總醫院實驗動物中心完成.材料:日本大耳傢兔25隻,雌雄各半,體質量1.75～2.25 kg,用于建立傢兔腎小毬硬化動物模型,併隨機分為正常組10隻和模型組15隻.方法:模型組30 g/L戊巴比妥鈉生理鹽水溶液(1 mL/kg)痳醉,開腹摘除左腎.正常組行假手術,不摘除腎髒,餘與上同.手術1週後,模型組註射阿黴素5 mg/kg,2 週後註射阿黴素3 mg/kg.正常組同步註射生理鹽水.主要觀察指標:于實驗前、造模後4,6,8週對兩組兔進行腎功能相關血液生化指標檢測,併留尿液測24 h尿蛋白量.于第2次註藥後8週分彆兩組隨機各取1隻兔腎組織,進行病理觀察.結果:①模型組腎髒略白,質地略韌,錶麵尚光滑.②模型組光鏡下可見細胞外基質增生明顯,繫膜區擴張,腎毬囊壁與腎小毬毛細血管拌粘連,小管上皮變性甚至萎縮齣現腎間質纖維化,間質炎細胞浸潤,呈現瀰漫性節段性腎小毬硬化等病理特徵.③與正常組傢兔比較,模型組傢兔總蛋白及白蛋白明顯下降,三酰甘油、總膽固醇、低密度脂蛋白膽固醇、尿素氮、肌酐均顯著升高,模型組傢兔尿蛋白含量于實驗第4週開始明顯升高,在實驗期間明顯高于對照組,但在第8週逐漸趨嚮平檯.④SPECT示:正常組腎小毬總濾過率為92.6 mL/min,模型組為33 mL/min;可見模型組右側腎髒腎小毬濾過率明顯下降.結論:單側腎切除聯閤阿黴素導緻傢兔的腎小毬硬化形成,併且腎功能及24 h尿蛋白定量有較明顯的階段性變化.
배경:단측신절제연합아매소유도적대서신소구경화모형상용우항신소구경화약물적사선화평개,단목전흔소유차방법유도토신소구경화모형적보도.목적:건립가토신소구경화동물모형,병관찰조모과정중동물적신장공능화조직병이학변화.설계、시간급지점:수궤대조동물실험,우2008-12/2009-05재해방군성도군구곤명총의원실험동물중심완성.재료:일본대이가토25지,자웅각반,체질량1.75～2.25 kg,용우건립가토신소구경화동물모형,병수궤분위정상조10지화모형조15지.방법:모형조30 g/L무파비타납생리염수용액(1 mL/kg)마취,개복적제좌신.정상조행가수술,불적제신장,여여상동.수술1주후,모형조주사아매소5 mg/kg,2 주후주사아매소3 mg/kg.정상조동보주사생리염수.주요관찰지표:우실험전、조모후4,6,8주대량조토진행신공능상관혈액생화지표검측,병류뇨액측24 h뇨단백량.우제2차주약후8주분별량조수궤각취1지토신조직,진행병리관찰.결과:①모형조신장략백,질지략인,표면상광활.②모형조광경하가견세포외기질증생명현,계막구확장,신구낭벽여신소구모세혈관반점련,소관상피변성심지위축출현신간질섬유화,간질염세포침윤,정현미만성절단성신소구경화등병리특정.③여정상조가토비교,모형조가토총단백급백단백명현하강,삼선감유、총담고순、저밀도지단백담고순、뇨소담、기항균현저승고,모형조가토뇨단백함량우실험제4주개시명현승고,재실험기간명현고우대조조,단재제8주축점추향평태.④SPECT시:정상조신소구총려과솔위92.6 mL/min,모형조위33 mL/min;가견모형조우측신장신소구려과솔명현하강.결론:단측신절제연합아매소도치가토적신소구경화형성,병차신공능급24 h뇨단백정량유교명현적계단성변화.
BACKGROUND: Rat models induced by unilateral nephrectomy combined with adriamycin are widely used in screening anti-drugs of glomerular sclerosis. However, few reports concerning this method on inducing rabbit model of glomerular sclerosisOBJECTIVE: To establish a rabbit model of glomerular sclerosis, and to observe the renal function and histopathological changes during model preparation. DESIGN, TIME AND SETTING: Randomized controlled animal experiment was performed in Laboratory Animal Center of Kunming General Hospital of Chengdu Military Region between December 2008 and May 2009. MATERIALS: Twenty-five Japanese big-ear rabbits, weighing 1.75-2.25 kg, half males and half females, were selected to establish glomerular sclerosis models, and randomly divided into normal (n=10) and model (n=15) groups. METHODS: The left kidney of rabbits in the model group was removed under anesthetized with 30g/L saline solution of sodium pentobarbital (1 mL/kg). Rabbits in the normal group underwent a similar surgical procedure without kidney removing. At 1 week after operation, 5 mg/kg adriamycin was injected into rabbits in the model group, 3 mg/kg adriamycin was reinjected 2 weeks later. Same volume of physiological saline was injected in the normal group. MAIN OUTCOME MEASURES: The renal blood biochemical indexes were detected prior to and at weeks 4, 6, and 8 after model preparation. One nephridial tissue was harvested from each group to undergo pathological observation at week 8 after the second medication. RESULTS: ①Kidney in the normal group presented slightly white, slightly tough texture with smooth surface. ②Pathological features of focal segmental glomerulosclerosis was showed in the model group under a light microscope, presented as extracellular matrix hyperplasia, mesangial region expansion, renal glomerular capillary wall ball mix adhesion, tubule degeneration, or even interstitial fibrosis, as well as interstitial infiltration of inflammatory cells. ③Compared to the normal group, the total protein and albumin was and decreased, triglyceride, total cholesterol, low density lipoprotein cholesterol, urea nitrogen, and creatinine were significantly increased in the model group. The urine protein content of rabbits in the model group was obviously increased at 4 weeks, gradually reached a platform after 8 weeks, which still greater than that of the normal group. ④SPECT showed that the glomerular filtration rate of the model group was notably decreased (33 mL/min) than the normal group (92.6 mL/min).CONCLUSION: The unilateral nephrectomy combined with adriamycin in rabbits results in the formation of glomerular sclerosis, renal function and 24 h urinary protein is more visible in the phase change.
