肾间质纤维化大鼠管周毛细血管病变的实验观察  

Peritubular micrangium injury in renal interstitial fibrotic rats

作　　者：谢敏[1,2] 周建华[1] 朱国琴[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院儿科,湖北武汉430030 [2]成都市妇女儿童中心医院儿童肾脏内科

出　　处：《临床儿科杂志》2012年第11期1054-1057,共4页Journal of Clinical Pediatrics

基　　金：国家自然科学基金资助项目(No.30472268)

摘　　要：目的观察单侧输尿管梗阻(UUO)诱导的大鼠肾间质纤维化模型中管周毛细血管的病变。方法将30只SD雄性大鼠随机分为假手术组、模型组,每组15只,采用左侧输尿管结扎术建立UUO模型,分别于术后第7、14、21天各处死5只,留取梗阻侧肾组织做病理学检查,用TUNEL法检测肾小管上皮细胞凋亡,免疫组化方法测定CD141、血管内皮生长因子(VEGF)表达水平。结果假手术组大鼠肾间质微血管未见明显病变,术后7、14、21 d,CD141阳性肾小管周围毛细血管(PTC)密度分别为(189.6±8.38)个/mm2、(185.2±11.12)个/mm2、(173.8±13.27)个/mm2;模型组大鼠肾间质微血管病变严重,主要集中于肾间质小管损伤明显区域,CD141阳性PTC数进行性减少,术后7、14、21 d分别为(116.8±8.92)个/mm2、(98.8±3.96)个/mm2、(62.2±7.01)个/mm2。假手术组大鼠各时间点均未见肾小管上皮细胞明显凋亡;模型组大鼠术后第7天已见肾小管上皮细胞凋亡,随梗阻时间延长,凋亡细胞呈明显增多趋势;假手术组大鼠肾间质各时间点均未见炎性细胞浸润,肾小管上皮细胞可见较多VEGF蛋白表达;模型组大鼠术后第7天肾间质出现大量炎性细胞浸润,第14、21天明显增多,而VEGF蛋白表达量呈逐渐降低趋势,炎性细胞浸润明显处几乎无VEGF表达。结论肾小管周毛细血管丢失与肾小管间质纤维化程度呈正相关,肾小管周围毛细血管病变在肾间质纤维化中起重要作用。Objectives To observe peritubular micrangium injury in renal interstitial fibrosis of unilateral ureteral obstruction （UUO） rats. Methods Thirty males SD rats were randomly divided into sham-operated （SHAM） and UUO group with 15 rats for each group. Five rats in each group were sacrificed on day 7, 14 and 21 after UUO or sham-operation. The kidney tissue of obstruction side was taken and was examined by morphological analysis. Apoptosis of tubular epithe- lial cells were examined by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling, the expression of CD141 and vascular endothelial growth factor （VEGF） were detected by immunohistochemical method. Results In the SHAM group, there were no significant injury of peritubular capillary （PTC）, and the numbers of CD141 positive PTC were （189.6~8.38）/mm2, （185.2~11.12）/mm2, （173.8=t=13.27）/mm2 on day 7, 14, 21. In the UUO group, PTC injured severely, the num- bers of CD141 positive PTC were progressively decreased with （116.8=t=8.92）/mm2, （98.8~3.96）/mm2, （62.2~7.01）/mm2 on day 7, 14, 21 respectively. No tubular epithelial cells apoptosis was observed in SHAM group, while apoptosis was found in UUO group on day 7 after operation （P〈0.05）. The number of apoptotic cells was increasing as the obstruction time getting longer. In SHAM group, there was no inflammatory cell infiltration observed with more VEGF presented in kidney tubular epithelial cell. While massive inflammatory cell infiltration was found in tubular interstitial area in UUO group on day 7 and increasing obviously on days 14 and 21 with decreasing VEGF protein. Nearly no VEGF protein was observed when infiltration became severe. Conclusions Renal peritubular capillary loss is positively correlated to interstitial fibrosis and plays an important role in interstitial fibrosis.

关 键 词：毛细血管  血管内皮生长因子 凋亡 大鼠 

分 类 号：R692[医药卫生—泌尿科学]