氧化应激对输尿管梗阻大鼠肾脏TGF-β1及其受体表达的影响  

Effects of oxidative stress on expressions of TGF-β1 and TGF-βRⅠ in rat kidney after unilateral ureteral obstruction

作　　者：张鹏宇[1] 阮颖新[2] 李春媚[3] 刘素雁[3] 

机构地区：[1]天津医科大学肿瘤医院检验科天津市肿瘤防治重点实验室,天津300060 [2]天津医科大学总医院肾内科,天津300052 [3]哈尔滨医科大学第二临床医学院肾内科,黑龙江哈尔滨150086

出　　处：《吉林大学学报（医学版）》2009年第3期400-405,F0002,共7页Journal of Jilin University：Medicine Edition

基　　金：国家自然科学基金资助课题(30800529);黑龙江省卫生厅科研基金资助课题(2007-305)

摘　　要：目的:探讨醛固酮(ALD)受体拮抗剂安体舒通对单侧输尿管梗阻(UUO)大鼠肾组织转化生长因子-β1(TGFβ-1)及其受体表达的影响,阐明其对肾脏的保护作用。方法:Wistar大鼠行左侧输尿管结扎术,分为UUO模型组(n=11)及安体舒通组(n=12),同时设假手术对照组(n=7)。术后第14天处死各组大鼠,行HE和Masson染色,观察肾脏病理变化;比色法测定肾组织羟脯氨酸(HYP)、丙二醛(MDA)和超氧化物歧化酶(SOD)含量;放免法测定血浆和肾组织ALD含量;免疫组织化学方法测定TGFβ-1和转化生长因子-βⅠ型受体(TGF-βRⅠ)的表达;Western blotting检测TGFβ-RⅠ的蛋白表达。结果:与假手术组比较,UUO组血浆和肾组织ALD含量增加(P<0.01),肾组织HYP及MDA含量明显增加(P<0.01),SOD含量下降(P<0.01),肾脏病理改变加重,肾组织TGFβ-1和TGFβ-RⅠ表达水平增加(P<0.05);与UUO组比较,安体舒通组血浆和肾组织ALD含量降低(P<0.01),肾组织HYP及MDA含量明显下降(P<0.05或P<0.01),SOD含量升高(P<0.05),肾脏病理改变评分降低(P<0.01),肾组织TGF-β1和TGFβ-RⅠ的表达减少(P<0.05)。结论:UUO模型致肾间质纤维化可能与ALD含量增高、氧化应激产物增加、TGFβ-1及其受体的表达增多有关联;且ALD受体拮抗剂安体舒通可部分拮抗该作用,保护肾脏。Objective To investigate the effects of oxidative stress on the expressions of transforming growth factor-β1 （TGF-β1） and transforming growth factor-β receptor I （TGF-βR I ） in rat unilateral ureteral obstruction （UUO） models. Methods Thirfty Wistar rats were randomly assigned into three groups： SOR group （shamoperated group, n=7）; UUO group （operation group, n=11）; US group （spironolactone 50 mg · kg^-1 · d^-1 by daily gastric garage after UUO, n= 12）. All the rats were killed 14 d after surgery. Renal fibrosis was assessed by the determination of tissue hydroxyproline （HYP） content. Malondialdehyde （MDA）, superoxide dismutase （SOD） as well as aldosterone （ALD） content were measured. Histological changes were observed by HE and Masson staining. Immunohistochemistry was performed to detect the expressions of TGF-β1 and TGF-βR I. Western blotting was used the determine the expression of TGF-13R I protein. Results Compared with sham group, the ALI） contents in plasma and kidney tissues in UUO group significantly increased （P〈0.01） ; the HYP and MDA levels in kidney tissues were also significantly increased （P〈0.01）, the SOD level was decreased （P〈 0.01）; the expression levels of TGF-β1 and TGF-βR I in kidney tissues were markedly increased （P〈0.05）. Compared with UUO group, the ALD contents in plasma and kidney tissues in US group were significantly decreased （P〈0.01）, the HYP and MDA levels in kidney tissues were also significanlty decreased （P〈0.05, P〈0.01）, the SOD level was increased （P〈0.05）, the expressions TGF-β1 and TGF-βR I in kidney tissues were markedly decreased （P〈0.05）. Conclusion The renal tubulointerstitiat fibrosis induced by UUO may be related to the elevation of aldosterone, the increased production of oxidative stress and downregulation of TGF-β1 and TGF-βR I. Aldosterone receptor antagonist spironolaetone can partly alleviate renal fibrosis.

关 键 词：安体舒通 输尿管梗阻 纤维化 氧化应激 转化生长因子Β1 受体 转化生长因子β 

分 类 号：R332[医药卫生—人体生理学] R693.2[医药卫生—基础医学]