Shankland S J, Ly H, Thai K, Scholey J W
Department of Medicine, University of Toronto, Ontario, Canada.
Circ Res. 1994 Nov;75(5):844-53. doi: 10.1161/01.res.75.5.844.
Increased glomerular capillary hydrostatic pressure (PGC) is an important hemodynamic determinant of glomerular injury, but the molecular events responsible for this association are poorly understood. PGC is normal in spontaneously hypertensive rats (SHR), but uninephrectomy leads to an increase in PGC and accelerated glomerulosclerosis. Since recent studies have implicated transforming growth factor-beta 1 (TGF-beta 1) and platelet-derived growth factor sought to determine if uninephrectomy increased mRNA levels for TGF-beta 1 and PDGF in glomeruli of SHR. Since treatment with the angiotensin-converting enzyme (ACE) inhibitor enalapril lowers PGC and prevents glomerulosclerosis in uninephrectomized SHR, we also sought to determine if ACE inhibitor lowered mRNA levels for TGF-beta 1 and PDGF in the glomeruli of uninephrectomized SHR. PGC increased from 53 +/- 1 to 64 +/- 1 mm Hg 1 week after uninephrectomy in SHR (P < .05). The increase in PGC was associated with a sixfold rise in mRNA levels for TGF-beta 1 and a twofold rise in mRNA levels for PDGF in glomeruli. mRNA levels for PDGF returned to normal 2 weeks after nephrectomy, but the increase in mRNA levels for TGF-beta 1 was sustained. An increase in TGF-beta 1 immunostaining was detectable in glomeruli 4 weeks after nephrectomy. Treatment with ACE inhibitor normalized PGC (51 +/- 1 mm Hg) and prevented the rise in glomerular mRNA levels for TGF-beta 1 and PDGF. We conclude that an acute increase in PGC leads to increased TGF-beta 1 and PDGF expression in the glomerulus, thus linking changes in PGC to cytokine gene expression.
肾小球毛细血管静水压（PGC）升高是肾小球损伤的一个重要血流动力学决定因素，但导致这种关联的分子机制却知之甚少。自发性高血压大鼠（SHR）的PGC正常，但单侧肾切除会导致PGC升高并加速肾小球硬化。由于最近的研究表明转化生长因子-β1（TGF-β1）和血小板衍生生长因子有作用，因此试图确定单侧肾切除是否会增加SHR肾小球中TGF-β1和血小板衍生生长因子（PDGF）的mRNA水平。由于用血管紧张素转换酶（ACE）抑制剂依那普利治疗可降低PGC并预防单侧肾切除的SHR发生肾小球硬化，我们还试图确定ACE抑制剂是否会降低单侧肾切除的SHR肾小球中TGF-β1和PDGF的mRNA水平。SHR单侧肾切除1周后，PGC从53±1毫米汞柱升至64±1毫米汞柱（P<.05）。PGC的升高与肾小球中TGF-β1的mRNA水平升高6倍以及PDGF的mRNA水平升高2倍相关。肾切除2周后，PDGF的mRNA水平恢复正常，但TGF-β1的mRNA水平升高持续存在。肾切除4周后，在肾小球中可检测到TGF-β1免疫染色增加。用ACE抑制剂治疗可使PGC恢复正常（51±1毫米汞柱），并防止肾小球中TGF-β1和PDGF的mRNA水平升高。我们得出结论，PGC的急性升高会导致肾小球中TGF-β1和PDGF表达增加，从而将PGC的变化与细胞因子基因表达联系起来。
