Manotham Krissanapong, Eiam-Ong Somchai, Eiam-Ong Somchit, Wannakrairot Pongsak, Praditpornsilpa Kearkiat, Chusil Saowaluck, Tungsanga Kriang
Nephrology Unit, Medicine, Lerdsin General Hospital.
J Med Assoc Thai. 2006 Aug;89 Suppl 2:S168-77.
Tubulointerstitial fibrosis plays an essential role in progression to end stage renal disease (ESRD) in various chronic renal failure (CRF) models including the 5/6 nephrectomy (5/6). The present study examines the renoprotective effect of citrate in the renal ablative model that is quite similar to CRF in human.
Male Wistar rats underwent 5/6 and were fed with tap water (5/6tap) or tap water containing 67 mEq/L citrate solution (5/6cit). Sham-operated rats (S) were divided into Stap and Scit groups. Renal function, renal histopathology, renal alpha-Smooth muscle actin (SMA), and renal transforming growth factor (TGF)-beta1 were determined immediately and at the 8th week after operation.
Following the surgery, the values of glomerular filtration rate (GFR) in the 5/6tap and the 5/6cit groups were 2.39 +/- 0.25 and 2.35 +/- 0.25 (mL/kg/min), respectively, both were significantly lower than sham groups (p < 0.05). At the eighth week, the 5/6tap group had progressively decreased GFR and had higher fibrosis score, increased alpha-SMA positive cells, and renal tissue TGF- beta1 when compared with the sham groups. The 5/ 6cit group, when compared with the 5/6tap group, had higher GFR (2.51 +/- 0.22 vs 1.17 +/- 0.33 mL/kg/min; p < 0.05), lower fibrosis score (1.83 +/- 0.88 vs 3.0 +/- 0.4, p < 0.001), lower alpha-SMA activity (159 +/- 2.9 vs 187 +/- 12.3 cells per 1000 interstitial cells, p < 0.05), and lower renal TGF-beta1 levels (1771.3 +/- 239.5 vs 4716.9 +/- 871.2 pg/mg protein, p < 0.005).
As such, in 5/6 nephrectomized rats, citrate therapy for eight weeks could decrease tubulointerstitial fibrosis mainly by reducing the heightened renal TGF-beta1 levels and additionally by attenuating the increased myofibroblast activity.
在包括5/6肾切除（5/6）在内的各种慢性肾衰竭（CRF）模型中，肾小管间质纤维化在终末期肾病（ESRD）进展过程中起关键作用。本研究在与人类CRF极为相似的肾切除模型中，检测柠檬酸盐的肾脏保护作用。
雄性Wistar大鼠接受5/6肾切除手术，分别给予自来水（5/6tap组）或含67 mEq/L柠檬酸盐溶液的自来水（5/6cit组）。假手术大鼠（S组）分为Stap组和Scit组。在术后即刻及术后第8周测定大鼠的肾功能、肾脏组织病理学、肾脏α-平滑肌肌动蛋白（SMA）以及肾脏转化生长因子（TGF）-β1。
术后，5/6tap组和5/6cit组的肾小球滤过率（GFR）值分别为2.39±0.25和2.35±0.25（mL/kg/min），均显著低于假手术组（p<0.05）。在第8周时，与假手术组相比，5/6tap组的GFR逐渐下降，纤维化评分更高，α-SMA阳性细胞增加，肾脏组织TGF-β1水平升高。与5/6tap组相比，5/6cit组的GFR更高（2.51±0.22对1.17±0.33 mL/kg/min；p<0.05），纤维化评分更低（1.83±0.88对3.0±0.4，p<0.001），α-SMA活性更低（每1000个间质细胞中159±2.9对187±12.3个细胞，p<0.05），肾脏TGF-β1水平更低（1771.3±239.5对4716.9±871.2 pg/mg蛋白，p<0.005）。
因此，在5/6肾切除大鼠中，为期8周的柠檬酸盐治疗主要通过降低升高的肾脏TGF-β1水平以及减弱增加的肌成纤维细胞活性，从而减少肾小管间质纤维化。
