肾淋巴管结扎对单肾切除大鼠的肾损害作用

Contralateral nephrectomy with disturbance of lymph circulation aggravate renal damage

目的:探讨肾淋巴循环障碍及单侧肾脏切除对大鼠肾脏功能结构的损害。方法:雄性Wistar大鼠,随机分为3组:双肾淋巴管结扎组(2KL),左肾淋巴管结扎伴右肾切除组(1KL),假手术组(sham)。分别在术后1、2、4、8周每组各处死6只。测定24 h尿蛋白和血尿肌酐。用PAS和Masson染色观察肾组织病理改变。用RT-PCR检测TGF-β1、Smad2/3、I型胶原(col I)mRNA的表达量;用免疫组化和Western blotting方法检测组织col I、TGF-β1、Smad2/3和磷酸化Smad2/3(p-Smad2/3)的蛋白表达量及主要表达部位。结果:2KL和1KL大鼠出现明显的蛋白尿和肾功能衰竭,1KL大鼠的肾脏损害尤其明显,随着时间推移逐渐加重,并出现明显的组织病理改变。2KL和1KL大鼠肾组织中col I、TGF-β1、Smad2/3、p-Smad2/3的蛋白和(或)基因表达水平也明显增高(P<0.01),且主要表达在肾小管上皮细胞及肾间质。1KL大鼠的表达也明显高于2KL大鼠。结论:肾淋巴循环障碍可导致大鼠肾脏功能及小管间质的损害,并随时间而加重。当淋巴循环障碍伴对侧肾切除时,损害明显加重。

AIM ： To investigate the time course of renal lesions induced by long - term ligation of renal hilar lymphatic vessels in rats with or without contralateral nephrectomy. METHODS： Animals were divided into three groups： rats with bilateral lymphatic ducts ligation （2KL）, rats with one renal ligation and another nephrectomy （1KL） and sham -operated rats （sham）. Proteinuria, serum creatinine value and creatinine clearance （Ccr） were monitored. Renal histology was examined under light microscopy. Further biochemical analysis was conduced by real - time PCR, immunostaining and Western blotting techniques. RESULTS： 1KL and 2KL rats developed severe proteinuria and renal failure. Histomor- phological changes appeared in ligated kidneys. Overexpression of transforming growth factor - β1 , Smad2/3, colⅠ genes and proteins were detected in 1KL and 2KL rats. Compared to 2KL rats, the changes in renal function and histology were more pronounced in 1KL rats. CONCLUSION： Disturbance of lymph circulation induces chronic renal failure and renal fibrosis, which is aggravated by lymphatic vessels ligation combined with contralateral nephrectomy