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目的:观察HSP47在单侧输尿管梗阻(unilateral ureteral obstruction,UUO)大鼠模型肾脏组织的表达情况,探讨HSP47在肾小管间质纤维化中的作用。方法:将SD大鼠随机分为模型组(UUO组)和假手术组(Sham组),每组8只。采用单侧(左)输尿管结扎方法,建立梗阻性肾小管间质纤维化大鼠模型。术后第14天处死动物。观察两组间蛋白尿和血肌酐水平,运用HE和Masson染色观察肾脏组织形态学改变,采用免疫组织化学方法检测HSP47、胶原Ⅳ(CollagenⅣ)的表达。结果:与Sham组比较,UUO组大鼠血肌酐水平升高,蛋白尿差异无统计学意义。光镜下UUO组大鼠肾组织出现不同程度的肾小管扩张、间质炎症细胞浸润,间质面积增宽、部分肾小管萎缩、肾小管上皮细胞空泡样变性。Masson染色结果显示UUO组大鼠肾组织胶原在肾小管周围、间质区显著增多。免疫组织化学结果显示UUO组大鼠肾组织HSP47表达显著增加,在肾小管周围、间质区表达增加最明显;CollagenⅣ表达显著增加,在肾小管基底膜、间质区表达增加最明显。结论:HSP47在UUO大鼠模型肾脏组织中表达上调,且与胶原表达部位一致,提示HSP47促进肾间质纤维化,且该作用与其促进胶原蛋白的合成有关。
OBJECTIVE: To observe the expression of HSP47 in renal tissue of unilateral ureteral obstruction (UUO) rat model and to explore the role of HSP47 in tubulointerstitial fibrosis. Methods: SD rats were randomly divided into model group (UUO group) and sham operation group (Sham group), with 8 rats in each group. Unilateral (left) ureteral ligation was used to establish a rat model of obstructive tubulointerstitial fibrosis. The animals were sacrificed on the 14th day after the operation. The proteinuria and serum creatinine were observed. The morphological changes of kidney were observed by HE and Masson staining. The expression of HSP47 and collagen Ⅳ were detected by immunohistochemistry. Results: Compared with Sham group, UUO group had elevated serum creatinine, but no significant difference in proteinuria. Under light microscope, the renal tissue of rats in UUO group showed different degrees of tubule dilatation, interstitial inflammatory cell infiltration, widening of interstitial area, partial tubular atrophy and vacuolar degeneration of renal tubular epithelial cells. The results of Masson staining showed that the amount of collagen in the renal tubules and the interstitium of the UUO group increased significantly. The results of immunohistochemistry showed that the expression of HSP47 in renal tissue increased significantly in UUO group and the expression of Collagen Ⅳ increased significantly in the peritumoral and interstitial region of tubules. The expression of HSP47 in the basement membrane and interstitial region increased most obviously. CONCLUSION: HSP47 is up-regulated in renal tissues of UUO rat model and consistent with the expression of collagen, suggesting that HSP47 may promote renal interstitial fibrosis, and this effect may be related to the promotion of collagen synthesis.