Hiong Law Chung, Voon Kiew Lik, Abdullah Nor Azizan, Sattar Munavvar A, Rahman Nazarina Abdul, Khan Abdul Hye, Johns Edward James
Department of Pharmacology, University of Malaya, Kuala Lumpur 50603, Malaysia.
Acta Pharmacol Sin. 2008 Apr;29(4):451-7. doi: 10.1111/j.1745-7254.2008.00772.x.
The aim of the present study was to investigate the effectiveness of transforming growth factor (TGF)-beta1 antisense oligodeoxynucleotides (ODN) in ameliorating deteriorated kidney function in rats with puromycin-induced chronic renal failure (CRF).
Saline, puromycin, puromycin+TGF-beta1 antisense ODN or puromycin+scrambled ODN were administered to unilaterally nephrectomized rats. Renal hemodynamic and excretory measurements were taken in the anaesthetized rats that had undergone surgical procedure.
It was observed that in the CRF rats, there was a marked reduction in the renal blood flow (RBF), glomerular filtration rate (GFR), severe proteinuria, and almost 6-fold increased fractional excretion of sodium (FE Na+) as compared to that in the control rats (all P<0.05). It was further observed that in the CRF rats, the treatment with TGF-beta1 antisense, but not scrambled ODN, markedly attenuated the reduction of RBF, GFR, and proteinuria and markedly prevented the increase of the FE Na+ (all P<0.05). In addition, the renal hypertrophy in the CRF group (P<0.05 vs non-renal failure control) was markedly attenuated after treatment with TGF-1 antisense ODN (P<0.05). Focal segmental glomerulosclerosis was evident only in the untreated and scrambled ODN-treated CRF groups. An interesting observation of this study was that in the CRF rats, although there was marked attenuating and preventive effects of the TGF-beta1 antisense ODN on the deteriorated renal functions, the antisense treatment did not cause any marked change in the renal expression of TGF-beta1 at the protein level.
Collectively, the data obtained suggests that TGF-beta1 antisense ODN possesses beneficial effects in puromycininduced chronic renal failure and that the deterioration in morphology and impaired renal function in this pathological state is in part dependent upon the action of TGF-beta1 within the kidney.
本研究旨在探讨转化生长因子（TGF）-β1反义寡脱氧核苷酸（ODN）改善嘌呤霉素诱导的慢性肾衰竭（CRF）大鼠肾功能恶化的有效性。
将生理盐水、嘌呤霉素、嘌呤霉素+TGF-β1反义ODN或嘌呤霉素+随机ODN给予单侧肾切除的大鼠。对接受手术的麻醉大鼠进行肾脏血流动力学和排泄测量。
观察到，与对照大鼠相比，CRF大鼠肾血流量（RBF）、肾小球滤过率（GFR）显著降低，蛋白尿严重，钠排泄分数（FE Na+）几乎增加了6倍（所有P<0.05）。进一步观察到，在CRF大鼠中，用TGF-β1反义ODN而非随机ODN治疗可显著减轻RBF、GFR的降低和蛋白尿，并显著阻止FE Na+的增加（所有P<0.05）。此外，CRF组的肾肥大（与非肾衰竭对照组相比，P<0.05）在用TGF-1反义ODN治疗后显著减轻（P<0.05）。局灶节段性肾小球硬化仅在未治疗和随机ODN治疗的CRF组中明显。本研究一个有趣的观察结果是，在CRF大鼠中，尽管TGF-β1反义ODN对肾功能恶化有显著的减轻和预防作用，但反义治疗并未引起肾脏TGF-β1蛋白水平表达的任何显著变化。
总体而言，所获得的数据表明TGF-β1反义ODN对嘌呤霉素诱导的慢性肾衰竭具有有益作用，并且这种病理状态下的形态恶化和肾功能受损部分依赖于肾脏内TGF-β1的作用。
