摘要
目的研究甲磺酸伊马替尼(STI571)改善单侧输尿管梗阻(UUO)小鼠肾间质纤维化的作用及机制。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STI57180、160mg/Kg灌胃。分别于术后第8,11d分别处死各组小鼠6只。光镜下观察肾脏病理改变。用免疫组化技术检测肾组织TGF-β1、PAI-1、α-SMA和PCNA的表达。结果治疗组的肾间质纤维化定量显著低于模型组(P<0·05),且不同剂量组之间存在显著差异(P<0·05)。模型组和治疗组左肾TGF-β1、PAI-1、α-SMA和PCNA的表达均随梗阻时间延长而逐渐增加,治疗组α-SMA和PCNA的表达较模型组明显减低(P<0·05)。结论甲磺酸伊马替尼可显著减轻UUO小鼠梗阻侧肾脏间质纤维化,下调α-SMA和PCNA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 and mechanism of imatinib mesylate （ST571） on the process of renal interstitial fibrosis following unilateral ureteral obstruction in mice. Methods 48 male mice were randomly assigned to four groups： shame operation group, UUO group, and 2 treatment groups. The mice in the treatment groups were intragastically given ST571 （80, 160mg/kg/d） after the operation of left ureter double ligature. The mice of each group were killed 8, 11 days after operation respectively. Immunohistochemistry was performed to investigate the protein expression of TGF-β1, PAI-1, α-SMA and PCNA in kidney. Results The degree of renal fibrosis in the treatment groups was much lower than that in the UUO group at 11th day after surgery （P〈0. 05） . There was a significant difference between the two treatment groups （P〈0. 05） . The expression of TGF-β1, PAI-1, α-SMA and PC- NA increased in both model group and treatment groups, α-SMA and PCNA were significantly lower in the treatment groups after surgery （P〈0. 05）. Conclusion Compared with the model group, ST571 significantly ameliorated the histological changes of the UUO renal tissue. The expression of α-SMA and PCNA decreased significantly in the treatment groups. It can reduce the deposition of extracellular matrix in the interstitium, and play a protective role in renal interstitial fibrosis.
出处
《中国组织化学与细胞化学杂志》
CAS
CSCD
2008年第3期232-237,共6页
Chinese Journal of Histochemistry and Cytochemistry
基金
国家自然科学基金资助(30070371)
关键词
甲磺酸伊马替尼
肾间质纤维化
单侧输尿管梗阻
Imatinib mesylate
Renal interstitial fibrosis
Unilateral ureteral obstruction
