中华老年多器官疾病杂志
中華老年多器官疾病雜誌
중화노년다기관질병잡지
CHINESE JOURNAL OF MULTIPLE ORGAN DISEASES IN THE ELDERLY
2014年
2期
131-134
,共4页
嘌罗霉素,氨基核苷%肾小球面积%肾小球硬化指数%nephrin%WT-1
嘌囉黴素,氨基覈苷%腎小毬麵積%腎小毬硬化指數%nephrin%WT-1
표라매소,안기핵감%신소구면적%신소구경화지수%nephrin%WT-1
puromycin aminonucleoside%glomerular area%glomerulosclerosis index%nephrin%WT-1
目的：应用嘌罗霉素氨基核苷（PAN）模型，通过观察临床、病理指标及足细胞特异性因子nephrin和肿瘤蛋白-1（WT-1）在足细胞的表达，了解足细胞损害在肾小球硬化过程中的重要作用。方法尾静脉注射PAN制作大鼠肾病模型，测定不同时间点的生化指标，处死大鼠，取其肾脏，石蜡包埋切片，PAS及免疫组化染色，测定肾小球硬化指数（GSI），肾小球面积（GA），nephrin及WT-1的表达，进行统计学分析。结果 PAN组在早期（第8天）表现为典型肾病综合征，后期（20周）表现为慢性肾炎。形态学方面，PAN组的GSI在4，14，20周均明显高于对照组（P＜0.05）。PAN组GA在14周时大于对照组（P＜0.01），但在20周时小于对照组（P＜0.001），并且20周时GSI与GA之间呈强负相关关系。PAN组nephrin表达在4，14，20周时与对照组比较均有所减少（P＜0.05），与此同时，WT-1的表达在14和20周时较对照组明显减少（P＜0.001）。结论（1）在肾炎发展中，随着时间延长，GSI增高，GA缩小，并且GSI和GA之间呈负相关。（2）在肾小球硬化发展中， nephrin和WT-1的表达进行性减少，说明有明显足细胞数量的减少。因此，足细胞的损伤与肾小球硬化密切相关。
目的：應用嘌囉黴素氨基覈苷（PAN）模型，通過觀察臨床、病理指標及足細胞特異性因子nephrin和腫瘤蛋白-1（WT-1）在足細胞的錶達，瞭解足細胞損害在腎小毬硬化過程中的重要作用。方法尾靜脈註射PAN製作大鼠腎病模型，測定不同時間點的生化指標，處死大鼠，取其腎髒，石蠟包埋切片，PAS及免疫組化染色，測定腎小毬硬化指數（GSI），腎小毬麵積（GA），nephrin及WT-1的錶達，進行統計學分析。結果 PAN組在早期（第8天）錶現為典型腎病綜閤徵，後期（20週）錶現為慢性腎炎。形態學方麵，PAN組的GSI在4，14，20週均明顯高于對照組（P＜0.05）。PAN組GA在14週時大于對照組（P＜0.01），但在20週時小于對照組（P＜0.001），併且20週時GSI與GA之間呈彊負相關關繫。PAN組nephrin錶達在4，14，20週時與對照組比較均有所減少（P＜0.05），與此同時，WT-1的錶達在14和20週時較對照組明顯減少（P＜0.001）。結論（1）在腎炎髮展中，隨著時間延長，GSI增高，GA縮小，併且GSI和GA之間呈負相關。（2）在腎小毬硬化髮展中， nephrin和WT-1的錶達進行性減少，說明有明顯足細胞數量的減少。因此，足細胞的損傷與腎小毬硬化密切相關。
목적：응용표라매소안기핵감（PAN）모형，통과관찰림상、병리지표급족세포특이성인자nephrin화종류단백-1（WT-1）재족세포적표체，료해족세포손해재신소구경화과정중적중요작용。방법미정맥주사PAN제작대서신병모형，측정불동시간점적생화지표，처사대서，취기신장，석사포매절편，PAS급면역조화염색，측정신소구경화지수（GSI），신소구면적（GA），nephrin급WT-1적표체，진행통계학분석。결과 PAN조재조기（제8천）표현위전형신병종합정，후기（20주）표현위만성신염。형태학방면，PAN조적GSI재4，14，20주균명현고우대조조（P＜0.05）。PAN조GA재14주시대우대조조（P＜0.01），단재20주시소우대조조（P＜0.001），병차20주시GSI여GA지간정강부상관관계。PAN조nephrin표체재4，14，20주시여대조조비교균유소감소（P＜0.05），여차동시，WT-1적표체재14화20주시교대조조명현감소（P＜0.001）。결론（1）재신염발전중，수착시간연장，GSI증고，GA축소，병차GSI화GA지간정부상관。（2）재신소구경화발전중， nephrin화WT-1적표체진행성감소，설명유명현족세포수량적감소。인차，족세포적손상여신소구경화밀절상관。
Objective To investigate the role of podocytes damage in the process of glomerular sclerosis by observing the clinical and pathological indices and the expression of nephrin and Wilms’ tumor-1 (WT-1) in the podocytes of puromycin aminonucleoside (PAN)-induced nephropathy model. Methods A single intravenous injection of PAN via tail vein of rats was carried out to establish nephropathy model, and those with positive urine protein were identified as successful establishment. Biochemical and pathological parameters were analyzed in the model rats and normal controls at 4 and 8 d, and at 4, 14 and 20 weeks after the model establishment for the chronic renal injuries evaluation. After the rats were sacrificed at 4, 14 and 20 weeks, their kidneys were taken out, embedded in paraffin, and stained with periodic acid-Schiff (PAS) for determination of glomerulosclerosis index (GSI) and glomerular area (GA). Immunohistochemistry assay was performed to detect the expression of nephrin and WT-1. Results The PAN models were successfully established, showing typical nephritic syndrome in the early stage (day 8), and chronic glomerular nephritis in the later stage (week 20). The GSI was significantly higher in PAN group than in the normal controls at 4, 14 and 20 weeks after establishment (P<0.05). The mean size of GA was significantly larger in PAN rats than in the normal controls at 14 weeks (P<0.01), but was obviously smaller at 20 weeks (P<0.01). Significantly positive correlation was found between GSI and GA at 20 weeks in the model group. The expression of nephrin was obviously decreased in PAN group at 4, 14 and 20 weeks (P<0.05), so was that of WT-1 at 14 and 20 weeks (P<0.001). Conclusion (1) GSI is increased, while GA is decreased along with the progression of nephritis, and there is a negative correlation between GSI and GA. (2) The expression of nephrin and WT-1 is reduced along with the progression of glomerular sclerosis, indicating the decrease of podocytes. Therefore, the podocyte damage is closely associated with glomerular sclerosis.
