前列腺素E1脂微球载体制剂对5／6肾切除大鼠肾小管上皮细胞转分化的影响

目的观察前列腺素E1脂微球载体制剂（Lipo-PGE1）对5／6肾切除大鼠肾小管上皮细胞-间充质细胞转分化（EMT）的影响。方法将大鼠随机分为假手术组、5／6肾切除模型组（模型组）和Lipo-POE1治疗组。使用Lipo-PGE1干预后第8周处死大鼠测定大鼠尿蛋白及肾功能，光镜观察肾组织病理改变，免疫组织化学法检测肾组织α-平滑肌肌动蛋白（mSMA）的表达。结果模型组大鼠24h尿蛋白排泄量、血尿素氮和血肌酐水平显著高于假手术组，肾小球和肾小管-间质病变显著，肾组织α-SMA表达明显增加；经过Lipo-PGE1治疗后，大鼠24h尿蛋白排泄量较模型组显著减少，肾功能明显改善，肾小球和肾小管-间质病变减轻，肾组织α-SMA表达较模型组显著下调。结论Lipo-PGE1能够显著下调5／6肾切除大鼠肾组织α-SMA表达，抑制肾小管上皮细胞转分化，这可能是其肾脏保护作用机制之一。

Effects of lipo-PGE1 on renal tubular epithelial-mesenchymal transdifferentiation in 5/6 nephrectomized rats

Objective To observe the renal tubular epitheliabmesenchymal transdifferentiation and the effects of lipo-prostaglandin E1 （prostaglandin E1 incorporated in lipid microspheres, Lipo- PGE1） in 5/6 nephrotomized rats,and explore the renal protective mechanisms of Lipo-PGE1. Methods The animal model was induced by 5/6 nephrotomy. Thirty male rats were divided into three groups randomly：5/6 nephrotomized group, Lipo-PGE1 treated group and sham-operated group. At the 8th week after therapy with Lipo PGE1, blood ureanitrogen（BUN）, creatinine （SCr） and 24-h urinary protein were detected. The glomerular and tubulointerstitial pathological changes were observed under the light microscopy. The renal protein expression of a-smooth muscle actin （α-SMA） was detected by using immunohistochemistry. Results 24-h urinary protein, BUN and Cr in 5/6 nephrotomized group were significantly higher than in sham-operated group, and the pathological changes of kidney in 5/6 nephrotomized group were more significant. The expression level of a-SMA in 5/6 nephrotomized group was obviously higher than in sham-operated group. After the treatment with Lipo-PGE1,24-h urinary protein, BUN and SCr were reduced obviously. The glomerular and tubulointerstitiai pathological changes were ameliorated obviously in Lipo-PGE1-treated group. The expression level of α-SMA was also obviously inhibited in Lipo-PGE1-treated group as compared with the 5/6 nephrotomized group. Conclusions Lipo-PGE1 can down-regulate the expression of α-SMA and restrain the process of epithelial-mesenehymat transdifferentiation in 5/6 nephrotomized rats. It may be one of the renal protec- tive mechanisms of Lipo-PGE1.