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维甲酸可改善肾切除术后的恢复并降低肾脏转化生长因子-β1的表达。性别相关影响。

Retinoic acid improves recovery after nephrectomy and decreases renal TGF-β1 expression. Gender-related effects.

作者信息

Delgadillo Dealmy, Barbier Olivier, Sierra Gerardo, Reyes Jose L

机构信息

Pharmacology Department, Center for Research and Advanced Studies, National Polytechnic Institute of Mexico (Cinvestav-IPN), C.P. 07360, Mexico City, Mexico.

出版信息

Fundam Clin Pharmacol. 2014 Apr;28(2):170-9. doi: 10.1111/fcp.12013. Epub 2012 Nov 28.

Abstract

End-stage renal disease is a cause for death worldwide. Renal transplant is a therapeutic alternative, restricted by the scant number of donors. Function of the donor kidney is under risk of adverse circumstances such as fibrosis, where profibrotic effect of transforming growth factor beta 1 (TGF-β1) plays a key role. Efforts to diminish risks of damage in the remnant kidney of the donor are required. Vitamin A represents one alternative. It has beneficial effects on some nephropathies, mainly those related to oxidative stress. It also participates in normal intrauterine renal development. We studied the effect of all-trans retinoic acid (ATRA), active form of vitamin A, on postnephrectomy compensatory growth, in male or female rats. Compensatory growth and renal function were evaluated on four experimental groups: Control without treatment (CTL), ATRA-treated intact rats (CTL + RA), nephrectomized rats (NFX), and ATRA-treated nephrectomized rats (NFX + RA). We evaluated glomerular function (inulin clearance), tubular function (fractional excretions of sodium and potassium), and urinary flow. Renal mass was also estimated. In ATRA-treated animals, compensatory growth was higher than in nephrectomized rats without treatment. Hyperfiltration after nephrectomy was less intense in ATRA-treated female than in male rats. In tubular functions, effect of ATRA was more evident in female than in male rats. Glomerular expression of TGF-β1 was lower in ATRA-treated animals than in controls. ATRA reduced intensity and duration of compensatory changes after nephrectomy, improving recovery.

摘要

终末期肾病是全球范围内的一个死亡原因。肾移植是一种治疗选择,但受限于供体数量稀少。供体肾的功能面临诸如纤维化等不利情况的风险,其中转化生长因子β1(TGF-β1)的促纤维化作用起关键作用。需要努力降低供体残余肾损伤的风险。维生素A是一种选择。它对一些肾病有有益作用,主要是那些与氧化应激相关的肾病。它还参与正常的子宫内肾脏发育。我们研究了维生素A的活性形式全反式维甲酸(ATRA)对雄性或雌性大鼠肾切除术后代偿性生长的影响。在四个实验组中评估代偿性生长和肾功能:未治疗的对照组(CTL)、接受ATRA治疗的完整大鼠(CTL + RA)、肾切除大鼠(NFX)以及接受ATRA治疗的肾切除大鼠(NFX + RA)。我们评估了肾小球功能(菊粉清除率)、肾小管功能(钠和钾的分数排泄)以及尿流。还估计了肾脏质量。在接受ATRA治疗的动物中,代偿性生长高于未治疗的肾切除大鼠。肾切除术后的高滤过在接受ATRA治疗的雌性大鼠中比在雄性大鼠中程度较轻。在肾小管功能方面,ATRA对雌性大鼠的影响比雄性大鼠更明显。接受ATRA治疗的动物中TGF-β1的肾小球表达低于对照组。ATRA降低了肾切除术后代偿性变化的强度和持续时间,改善了恢复情况。

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