乌司他丁对脓毒症急性肾损伤大鼠内皮素-1水平的影响及其肾脏保护作用

Ulinastatin prevents sepsis - induced acute kidney injury via down regulating the endothelin - 1 level

目的观察乌司他丁（UlinastatinUTI）对脓毒症急性肾损伤（acutekidneyinjury，AKI）大鼠血浆内皮素-1（endothelin-1，ET-1）水平及肾组织ET-1基因表达水平的影响，探讨乌司他丁对脓毒症急性肾损伤大鼠肾脏的保护作用。方法36只雄性sD大鼠随机分为三组（每组n=12）：假手术（Sham）组、盲肠结扎穿孔（CLP）组、CLP＋乌司他丁（UTI）组。CLP组分时间点（0h、3h、6h、12h）测定血浆ET-1水平。12h后取动脉血及肾组织，测定血浆肌酐（Cr）、尿素氮（BUN）及ET-1水平，并测定ET-1mRNA在肾脏的表达水平，观察肾脏组织病理改变及超微结构改变。结果与Sham组比较，CLP组血浆Cr、BUN、ET-1及肾脏组织ET-1mRNA水平显著升高（P〈0．05）；与CLP组比较，CLP＋UTI组血浆Cr、BUN、ET-1及肾脏组织ET-1mRNA水平显著降低（P〈0．05）。血浆ET-1水平6h达高峰。Sham组肾脏形态学及超微结构正常。CLP组肾脏光镜下可见肾小球体积缩小，肾小管上皮细胞变性、坏死脱落、管型形成，肾间质中性粒细胞浸润等改变；电镜下可见基底膜增厚、足突细胞排列紊乱、融合、线粒体肿胀、嵴断裂、空泡变性等改变。CLP＋UTI组肾脏形态学及超微结构改变较CLP组好转。结论乌司他丁对脓毒症急性肾损伤大鼠的肾脏具有保护作用，其机制可能与降低血浆ET-1水平及降低ET-1mRNA在肾脏中的表达有关。

Objective To investigate the renal protective effects of ulinastatin in rats with sepsis -induced acute kidney injury（AKI）. Methods Sepsis model was reproduced in rats with cecal ligation and puneture（CLP）, thirty- six Sprague Dawley（SD） rats were randomly divided into three groups（ t~ = 12 ） ： sham - operation group, CLP group and CLP ＋ Ulinastatin（UTI） group. Endothelin - l （ ET - 1 ） was determined by radioimmunoassay, renal ET - 1 gene expression was determined by semi - quantitative RT - PCR detection, and observing the morphological and ultrastrueture changes of the kidney. Results Compared with sham group, plasma Cr and BUN were increased in CLP group （ P 〈 0.05 ） , the same as ET - 1 level in plasma, which was highest by six hours. Compared with CLP group, the plasma Cr, BUN and ET - 1 level was significantly decreased in CLP ＋ UTI group （ P 〈 0.05） ; and the level of ET - 1 mRNA was significantly increased in CLP group （ P 〈 0. 05 ）, and decreased in CLP ＋ UTI group （ P 〈 0.05 ）. Morphological and ultrastructural morphology of kidney insham group was normal, the CLP group has several changes, such as thickening of the basement membrane, the cell array foot protrusion disorder, integration, mitochondrial swelling, ridge fault, degeneration, and other changes. Compared with CLP group, morphological and uhrastructural changes was decreased in CLP ＋ UTI group. Conclusion Ulinastatin can protect the kidney in rats with sepsis - induced AKI, which maybe by decreasing ET - 1 levels in plasma as well as ET - 1 gene expression levels in renal.