Nakamura T, Ebihara I, Nagaoka I, Osada S, Tomino Y, Koide H
Department of Medicine, Juntendo University School of Medicine, Tokyo, Japan.
Ren Physiol Biochem. 1993 May-Jun;16(3):105-16. doi: 10.1159/000173756.
The present study was carried out to determine whether transforming growth factor-beta, insulin-like growth factor-I and basic fibroblast growth factor mRNA levels were correlated with disease activity in NZB/W F1 mice, an animal model of systemic lupus erythematosus. Levels of mRNA for these three growth factors increased significantly as nephritis progressed in these mice. At 48 weeks of age, transforming growth factor-beta, insulin-like growth factor-I, and basic fibroblast growth factor mRNA levels showed a 11- (p < 0.001), 10- (p < 0.001), and 8-fold (p < 0.001) increase, respectively, in the renal cortex of NZB/W F1 mice when compared with NZW control mice. In NZW kidneys, these mRNA levels showed little change throughout the study period. At 24 weeks of age, NZB/W F1 mice were divided in 2 groups that received either methylprednisolone or saline injections for 24 weeks. The development of histological lesions and the increase in these growth factor mRNA levels in the kidneys of NZB/W F1 mice were both suppressed by methylprednisolone. These results indicate that the transforming growth factor-beta, insulin-like growth factor and basic fibroblast growth factor may play a role in the progression of murine lupus nephritis and that methylprednisolone may be an effective treatment at the transcription level of these growth factor genes for this type of nephritis.
本研究旨在确定转化生长因子-β、胰岛素样生长因子-I和碱性成纤维细胞生长因子的mRNA水平是否与系统性红斑狼疮动物模型NZB/W F1小鼠的疾病活动相关。随着这些小鼠肾炎的进展,这三种生长因子的mRNA水平显著升高。在48周龄时,与NZW对照小鼠相比,NZB/W F1小鼠肾皮质中转化生长因子-β、胰岛素样生长因子-I和碱性成纤维细胞生长因子的mRNA水平分别增加了11倍(p < 0.001)、10倍(p < 0.001)和8倍(p < 0.001)。在NZW小鼠的肾脏中,这些mRNA水平在整个研究期间几乎没有变化。在24周龄时,将NZB/W F1小鼠分为两组,分别接受甲基强的松龙或生理盐水注射,持续24周。甲基强的松龙抑制了NZB/W F1小鼠肾脏组织学病变的发展以及这些生长因子mRNA水平的升高。这些结果表明,转化生长因子-β、胰岛素样生长因子和碱性成纤维细胞生长因子可能在小鼠狼疮性肾炎的进展中起作用,并且甲基强的松龙可能是针对这类肾炎在这些生长因子基因转录水平的有效治疗方法。