阿霉素大鼠肾病模型足细胞线粒体体视学分析

目的探讨大鼠肾脏中足细胞线粒体形态和数目与阿霉素大鼠肾病模型蛋白尿的关系。方法清洁级雄性SD30只大鼠尾静脉分别注射阿霉素0．7mg／100g体重和生理盐水,分别在注射后2W（对照组3只,阿霉素组3只）、4w（对照组3只,阿霉素组6只）和6W（对照组8只,阿霉素组7只）处死大鼠,取肾皮质标本进行透射电镜观察,对线粒体形态和密度进行体视学分析。结果阿霉素组大鼠4W出现蛋白尿,持续至6W。对照组大鼠肾组织足细胞内线粒体多呈椭圆形,阿霉素组大鼠足细胞线粒体形态多样,大小不一。统计分析未发现阿霉素组和对照组大鼠足细胞线粒体面积、周长、形状因子和最大长宽比的差异。注射2W后蛋白尿出现前,阿霉素组大鼠肾组织足细胞内线粒体面数密度明显增多,与对照组比较差异具有统计学意义（0．17±0．00VS．0．14±0．01,t=6．173,P〈0．01）,同时线粒体相对于细胞体的表面积密度有增加趋势（0．78±O．03VS．0．71±0．04,t=-2．526,P=0．065）。注射6w后,阿霉素组大鼠足细胞线粒体面数密度无显著变化,线粒体相对于足细胞胞浆的表面积密度显著减少（0．71±0．11VS．0．87±0．12,P=0．02）。结论线粒体多形性改变参与阿霉素大鼠肾病模型蛋白尿的发生,足细胞线粒体数量增多是阿霉素大鼠肾病模型蛋白尿发生过程中的早发事件,线粒体膜表面积密度下降参与足细胞损伤及阿霉素大鼠肾病的进展。

Sterological analysis of podocyte mitochondria in adriamycin nephropathy rats

Objective To disclose the relationship between mitochondrial morphology, density and pro- teinuria in adriamycin nephropathy rats. Method Thirty Sprague Dawley rats of clean grade were divided into adriamycin group and control group. In adriamycin nephropathy group, rats were given adriamycin at dosage of 0.7 mg/100 g body weight by tail vein injection. The control rats received equal volume of sa- line. At 2 weeks （ control group = 3, adriamycin group = 3） , 4 weeks （ control = 3, adriamycin group = 6） and 6 weeks （control = 8, adriamycin group = 7） after adriamycin injection, the rats were sacrificed and kidneys were harvested for preparation of ultra-thin sections. Electron microscopy was performed, and podocyte mitochondrial morphology was observed. Sterological analysis was performed on morphology and density of mitochondria in podocytes. Results 4 weeks after adriamycin injection, the rats developed proteinuria until 6 weeks. Mitochondria in the podocytes from control rats showed ellipsoid shape. Differ- ent shaped and sized mitochondria were observed in podocytes of the adriamycin nephropathy rats. No sig- nificant statistical difference was revealed in the mitochondrial area, circumference, form factor and aspect ratio between adriamycin and control groups. Before development of proteinuria, the mitochondrial density increased significantly at 2 weeks after adriamycin injection compared with that in control rats （0.17 ± 0.00 vs. 0.14±0.01, t = 6. 173, P 〈0.01 ）. Meanwhile, the surface density of mitochondria showed an increasing trend （0.78 ±0.03 vs. 0.71±0.04, t = -2. 526, P =0. 065）. 6 weeks after adriamycin injection, the surface density of mitochondria decreased significantly compared with that in the control rats （0.71 ±0. 11 vs. 0. 87 v 0. 12, P = 0. 02）, the density of mitochondria did not change significantly Conclusions Dysmorphic mitochondria are involved in the development of proteinuria in adriamycin ne- phropathy. The increase of mitochondrial density is an earl