骨髓源干细胞促进进展性肾小球硬化模型肾小球的修复再生  

Bone marrow-derived stem cells promote glomerular repair and regeneration in progressive glomerulosclerosis rat model

作　　者：邢丽[1] 张道法[1] 宋淑敏[1] 王岑岑[1] 戚思华[2] 杨宝峰[3] 李冰[1] 

机构地区：[1]哈尔滨医科大学附属第二医院肾内二科,150086 [2]哈尔滨医科大学附属第四医院麻醉科 [3]哈尔滨医科大学药理教研室

出　　处：《中华肾脏病杂志》2011年第11期850-853,共4页Chinese Journal of Nephrology

基　　金：国家自然科学基金面上项目（81070569,30771006）;中国博士后科学基金特别资助（第三批）

摘　　要：目的研究骨髓源干细胞（BMDSC）移植对进展性肾小球硬化模型大鼠的作用，同时观察移植的BMDSC能否分化为肾脏内皮细胞和促进肾小球毛细血管修复再生。方法把携带增强型绿色荧光蛋白（EGFP）转基因SD大鼠的BMDSC移植于EGFP—SD大鼠制成嵌合性大鼠。注射抗Thy-1．1抗体，30min后再予切除右侧肾脏制成进展性肾小球硬化模型。按是否给予BMDSC治疗分为非治疗组及治疗组，每组10只，实验期限12周。在不同时间点，检测肾功能，并进行光镜、免疫荧光病理检查。观察移植后大鼠情况，以及移植的BMDSC是否分化为肾脏内皮细胞和促进肾小球毛细血管修复再生。结果12周时，非治疗组大鼠仅有3只存活，余7只分别死于抗体注射后第2、7、9、11周；治疗组大鼠9只存活，仅1只死于第10周。与非治疗组比较，治疗组肾功能明显改善[BUN（43．55±29．06）比（76．58±66．19）mmol／L，Scr（138．79±75．14）比（233．38±164．43）μmol／L]。第3、7、14、28天时两组24h尿蛋白量差异无统计学意义，而在第42、56、84天时，治疗组显著低于非治疗组。非治疗组可见严重系膜细胞和基质增生及。肾小球硬化，而治疗组上述增生与硬化明显减轻；非治疗组肾小球硬化指数和系膜细胞增生指数显著高于治疗组，差异有统计学意义。治疗组肾小球可见多个BMDSC，细胞数显著多于非治疗组和正常嵌合鼠。用鼠内皮细胞标记抗体RECA-1进行双重免疫荧光染色显示，治疗组有更多BMDSC参与了肾小球内皮细胞的修复及再生，并且显著促进了肾小球毛细血管的修复再生。结论BMDSC静脉输入对进展性肾小球硬化有治疗作用，BMDSC可分化成内皮细胞，并可促进肾小球毛细血管的修复再生。Objective To investigate the protective role of bone marrow-derived stem cells （BMDSCs） in progressive glomerulosclerosis rats, and to observe whether BMDSCs promote glomerular repair and regeneration. Methods Progressive glomerulosclerosis was induced in enhanced green fluorescent protein （EGFP） bone marrow chimeric rats by injecting with anti-Thy- 1.1 antibody, followed by unilateral nephrectomy. Subsequently, these rats were treated with either BMDSCs infusion （treatment group, 10 rats） or phosphate-buffered saline （untreated group, 10 rats）. Renal function and histological alterations were examined at week 12 after Thyl.1 antibody injection. Repair and regeneration of glomerular endothelial cells was detected by immunofluorescence. Results Only 3 rats survived in untreated group, other 7 rats died at week 2, 7, 9, 11 after antibody injection. In treatment group, 9 rats survived at week 12, only 1 rat died at week 10. The BUN and Scr were significantly lower in treatment group as compared to untreated group [BUN（43.55±29.06） vs （76.58±66.19） mmol/L, Scr （138.79±75.14） vs （233.38± 164.43） μmol/L]. Proteinuria was not significantly different between two groups at day 3, 7, 14 and 28, while it was significantly decreased at day 42, 56 and 84 in treatment group compared with untreated group. Light microscopy showed that there was severe diffuse mesangial cell proliferation, mesangial matrix expansion and glomerulosclerosis in untreated group, and such changes were ameliorated in treatment group. The mesangial expansion index and glomerular sclerosis index in untreated group was significantly higher than those in treatment group. More BMDCs were recruited into the glomeruli and differentiated into glomerular endothelial ceils in treatment group as compared with untreated group. Double immunofluorescence stain also demonstrated that BMDSCs infusion promoted glomerular capillary repair and regeneration. Conclusion BMDSCs infusion can improve renal function and histological changes

关 键 词：骨髓 干细胞 肾小球 纤维化 内皮细胞 增强型绿色荧光蛋白-转基因大鼠 

分 类 号：R692.6[医药卫生—泌尿科学]