兔单侧输尿管梗阻模型中TGF-β1变化的意义

Significance of change of TGF-β1 in rabbit model with unilateral ureteral obstruction

目的 改进单侧输尿管梗阻模型的建立方法 ,探讨TGF - β1变化的意义及可能的治疗措施。 方法 对 40只兔进行分组实验。输尿管梗阻模型的方法 ,以输尿管内置导管 ,并结扎之。对肾脏进行病理学观察。测定血、尿中菊糖和TGF - β1的浓度。用统计学方法进行分析。结果 在 40只兔中 ,31例完成了系列实验。 4例死于麻醉 ,4例因导管插入过长引起肾盂内积血 ,1例感染。梗阻侧肾脏呈现出梗阻引起的一系列病理改变。梗阻侧尿液中菊糖浓度明显低于正常值 ;而梗阻侧尿液中TGF - β1浓度明显高于正常侧。 结论采用输尿管内置管建立的梗阻动物模型 ,易于进行标本的反复收集 ;输尿管梗阻引起肾小球滤过率下降 ,而TGF - β1mRNA表达增加 ,TGF - β1合成增加 ,引起肾间质纤维化。抗TGF - β1抗体对抗TGF - β1治疗、修饰素和抑制AngⅡ治疗 ,对减少肾间质纤维化 。

Objective To establish an animal model of Unilateral Ureteral Obstruction(UUO), so as to explore significance of transforming growth factor β1 (TGF-β1) in UUO. Methods A tube was inserted into one side ureter of rabbit, and then the end of the tube was ligated. The pathological change of kidney was observed by microscope, the concentrations of inulin and TGF-β1 in urine and blood were examined analyzed by statistic. Results Among 40 rabbits, the trials had been finished in thirty-one cases. 4 rabbits died during anaesthesia, 4 rabbits had hematonephrosis because of long distance tube inserted, and infection happened in 1 rabbit. Pathological changes were appeared in the kidney with ureteral obstruction. Uric inulin of obstructed kidney was lower than normal; and uric TGF-β1 of obstructed kidney was higher than normal. Conclusions The animal model of UUO by inserting tube into ureter was established successfully, it was easy to collect of urine repeatedly in this modle. The glomerular flow rate decrease because of obstruction of ureter. The expression of TGF-β1 mRNA and synthesis of TGF-β1 increased. It caused the interstitial fibrogenesis in renal. Anti-TGF-β1 antibody, decorin and inhibitor of Ang II are important for decreasing renal interstitial fibrogenesis and improving renal function. Rabbit; UUO; Animal model; TGF-β1