甲磺酸伊马替尼对单侧输尿管梗阻小鼠肾脏间质纤维化的影响  

Effects of Abl Protein Tyrosine Kinase on Renal Interstitial Fibrosis in UUO Mice

作　　者：刘蔚[1] 何晓峰[1] 赵晓琴[1] 邵菊芳[1] 刘晓城[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院肾内科,武汉430030

出　　处：《华中科技大学学报（医学版）》2008年第5期595-599,共5页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

摘　　要：目的研究甲磺酸伊马替尼(STI571)对单侧输尿管梗阻(UUO)小鼠肾间质纤维化的防治作用。方法48只小鼠随机分为4组:假手术组,模型组,小剂量治疗组[80mg/(kg.d)],大剂量治疗组[160mg/(kg.d)]。采用左侧输尿管双结扎的方法建立UUO模型,治疗组每天以80、160mg/kgSTI571灌胃。于术后第8、11天分别处死各组小鼠6只。用酸水解-比色法测定肾组织胶原的含量;用免疫组化技术检测肾脏纤维连结蛋白(FN)的沉积。利用逆转录-聚合酶链反应(RT-PCR)观察FN和Ⅲ型胶原(ColⅢ)mRNA表达。结果治疗组的肾组织胶原含量在术后第11天显著低于模型组(P<0.05),且不同剂量组之间差异有显著性意义(P<0.05)。模型组和治疗组左肾FN含量随梗阻时间延长而逐渐增加,术后第11天治疗组的表达较模型组明显减低(P<0.05),且不同剂量组之间存在显著差异(均P<0.05)。模型组FN和ColⅢα1mRNA表达随梗阻时间延长而逐渐增加,在对应时间点上治疗组FN和ColⅢα1mRNA表达较模型组明显减低(均P<0.05),且不同剂量组之间存在显著差异(P<0.05)。结论STI571可显著减轻UUO小鼠梗阻侧肾脏间质纤维化,下调FN和ColⅢ的表达,减少肾间质细胞外基质的沉积,对UUO小鼠肾间质纤维化有一定防治作用。Objective To evaluate the effect of imatinib mesylate （STI571） on the process of renal interstitial fibrosis following unilateral ureteral obstruction （UUO） in mice. Methods Forty-eight male mice were randomly assigned to 4 groups： sham operation group, UUO group, low dose of STI571- and high dose of STI571-treated groups. The mice in treatment groups were given with ST571 （80, 160 mg/kg every day） after operation through intragastric administration. The mice were operated on by left ureter double ligature. Mice of each group were killed at 8th and 11th day after operation respectively. The content of total collagen from each group was examined by acidolysis and shade selection. Immunohistochemistry method was used to detect the protein expression of fibronectin （FN） in kidney. Reverse transcription polymerase chain reaction （RT-PCR） was used to examine the expression of FN and Col Ⅲ α1 mRNA. Results The degree of renal fibrosis in treatment group was much milder than in UUO group at 11th day after surgery （P〈0.05）. There was significant difference between the two treatment groups （P〈0.05）. The expression of FN and Col Ⅲ α1 was increased in a time-dependent manner in both UUO group and treatment group, but it was significantly lower in treatment group at 11th day after surgery （P〈0.05）. There was significant difference between the two treatment groups （P〈0.05）. Conclusion Compared to UUO group, STI571 significantly ameliorated the histological changes of the UUO renal tissue, down-regulated the expression of FN and reduced the deposition of extracellular matrix in the interstitium. STI571 played a protective role in the renal interstitial fibrosis.

关 键 词：甲磺酸伊马替尼 肾间质纤维化 单侧输尿管梗阻 

分 类 号：R322.6[医药卫生—人体解剖和组织胚胎学]