大鼠单侧输尿管梗阻模型肾脏足细胞损伤及转化的研究

Injury and epithelial-mesenchymal transition of rat podocytes in response to unilateral ureterai obstruction

目的研究大鼠单侧输尿管梗阻模型中肾脏足细胞损伤及表型转化情况。方法制作单侧输尿管梗阻模型，观察生后1d、2周、2个月SD大鼠单侧输尿管梗阻后肾脏病理改变，观察肾脏足细胞凋亡的发生和表型转化情况。结果输尿管梗阻后肾脏肾盂扩张，肾皮质逐渐变薄，低龄大鼠肾脏病变较大龄鼠明显。随梗阻时间延长，肾脏损害进行性加重。实验组均为足细胞最先发生凋亡，生后1d大鼠术后4h足细胞发生凋亡，2个月大鼠术后1d足细胞发生凋亡。单侧输尿管梗阻术后1dN见足细胞发生表型转化，术后3d可见肾小管上皮细胞发生表型转化。结论单侧输尿管梗阻引起肾脏损伤，随着肾积水程度加重，肾脏损害加重。而且低年龄组大鼠肾脏病理改变较高年龄组早且严重。单侧输尿管梗阻导致足细胞及肾小管上皮细胞凋亡，且足细胞凋亡早于肾小管上皮细胞。同时单侧输尿管梗阻还诱发足细胞转化为巨噬细胞，足细胞发生上皮间质转化早于小管上皮细胞。

Objective To investigate the injury and epithelial-mesenchymal transmon ot rat podocytes induced by unilateral ureteral obstruction. Methods Sprague-Dawley rats were divided into 3 groups according to age： 1 day after birth （D1）, 2 weeks old （W2）, and 2 months old （M2）. The SD rats were subjected to surgery to create unilateral ureteral obstruction. After a study period, the rats were sacrificed and their kidney were harvested for histological study, TUNEL staining and im- munofluorescence assays. The histological and phenotypic changes in podocytes were also studied. Re- sults Unilateral ureteral obstruction was successfully created on all rats as being proven by hydrone- phrosis and damage of the kidney. Meanwhile, apoptotic podocytes were found to be significantly in- creased in newborn rats 4 hours after unilateral ureteral obstruction, which happened earlier than that in 2 month old rats. Podocytes presented mesenchymal characteristics I day after the operation, and phenotypic changes in tubular epithelial cell happened 3 days after unilateral ureteral obstruction. Con- clusions These results show that unilateral ureteral obstruction cause more severe damage on podo- cytes of younger rats. And the apoptosis and phenotypic changes of podocytes induced by unilateral u- reteral obstruction happen earlier than that in tubular epithelial cells.