Prevention of glomerulosed erosis and tubul ointerstitial fibrosis : the effect of antisense ologonucleotide of type I procollagen C-proteinase enhancer protein

众所周知，无论原发病是什么，进行性肾损伤都以肾小球硬化和肾小管间质纤维化为特征，这是慢性肾功能衰竭的共同病理特征。本研究旨在探讨肾脏纤维化的机制，首先检测I型前胶原C-蛋白酶增强蛋白PCPE的表达，该蛋白是最近由Ogata I克隆的，同一作者已证明PCPE在肝纤维化中起重要作用。我们使用培养的大鼠系膜细胞、正常大鼠肾脏和5/6肾切除大鼠肾脏通过Western印迹分析检测了其在肾脏中的表达，并且我们不能检测到其在肾脏中的表达。我们还用北方印迹分析检测了其mRNA的表达，也没有检测到。因此，我们认为PCPE在肾脏纤维化的发病机制中起次要作用，我们还研究了白三烯B4（LTB 4）在肾脏疾病进展中的作用。采用高脂血症大鼠模型，用LTB_4拮抗剂治疗。该治疗显著改善了这些动物的肾损伤。然后我们检测了白三烯A4水解酶mRNA在大鼠肾单位中的分布，发现它在肾小球和肾小管中都有表达。这些结果表明，在肾脏中合成的LTB 4在进行性肾损伤的发病机制中起重要作用。

It is well known that, whatever the underlying original disease, progressive renal injury is characterized by glomeruloscl erosisand tubulointerstitial fibrosis, which are the common pathological features of chronic renal failure. We have planned the present study to investigate the mechanism of fibrosis in the kidney.First we examined the expression of type I procollagen C-proteinase enhnacer protein, PCPE, which was recently cloned by one of the investigators, Ogata I.By the same author PCPE has been to shown to play an important role in liver fibsosis. We have examined its expression in the kidney by Western blot analysis using cultured rat mesangial cells, normal rat kidney, and 5/6 nephrectomized rat kidney, and we could not detect its expression in the kidney. We also examined the expression of its mRNA by Northern blot analysis, and we could not detect it, neither. So we have concluded that PCPE plays minor role in the pathogenesis of renal fibrosis.We also examined the role of leukotrine B4(LTB4)in the progression of renal diseases. We made hyperlipidemia-induced renal injury in rats, and treated these rats with LTB4 antagonist. This treatment markedly ameliorated kidney injury in these animals. Then we examined the distribution of leukotriene A4 hydrolase mRNA expression in rat nephronsegments, and found that it is present both in glomeruli and tubular segments. These result suggest the important role of LTB4 synthesized in the kidney in the pathogenesis of progressive renal injuries.