全反式维甲酸对大鼠残余肾功能的保护作用及其机制

目的：研究全反式维甲酸(atRA)能否延缓大鼠残余肾功能的丧失，并探讨其可能机制。 方法： Wistar大鼠40只，采用5/6肾大部切除大鼠模型，分别给予5 mg·kg-1·d-1（A1组，n=8）、10 mg·kg-1·d-1（A2组，n=8）、20 mg·kg-1·d-1（A3组，n=8）的atRA灌胃，单纯肾大部切除非干预组（NX组，n=8）和假手术组（sham组，n=8）为对照。采用反相高效液相色谱检测大鼠血浆atRA浓度；肾脏病理切片采用PAS染色，计算肾小球硬化指数；应用免疫组化和Western blotting等方法观察转化生长因子β1（TGFβ1）在残余肾组织上的分布水平。 结果： 3个不同剂量的atRA组血药浓度高出NX和sham组10倍以上，并呈现出同给药剂量相吻合的浓度梯度。肾小球硬化评分结果表明，atRA 干预的大鼠肾小球硬化明显轻于NX组，其中A3组硬化程度明显轻于A1组和A2组，P<0.05；A1组和A2组无显著差异，sham组无硬化表现； NX组肾小球TGFβ1表达量最多，atRA干预的3个组明显少于sham组，但A1、A2、A3组间无差异。 结论： atRA能减轻5/6肾大部切除大鼠残余肾硬化，可能是通过抑制TGFβ1起作用。

The renoprotective role of all-trans retinoic acid in retarding rat glomerulosclerosis with 5/6 nephrectomy

AIM: To explore if all trans retinoic acid (atRA) retards glomerulosclerosis of rats with 5/6 nephrectomy. METHODS: Wistar male rats were operated by subtotal nephrectomy and were randomly divided into A1 (5 mg·kg-1·d-1 atRA), A2 (10 mg·kg-1·d-1 atRA), A3 (20 mg·kg-1·d-1 atRA) and NX (vehicle) groups. Each group included 8 rats. 8 health rats were assigned as sham-operation group (sham group). Animals were sacrificed 10 weeks after treatment. The concentrations of plasma atRA were measured by reversed phase high performance liquid chromatography (RP-HPLC). Glomerulosclerosis was evaluated by glomerulosclerosis index system. The expression of transforming growth factor-beta 1 (TGFβ1) was measured by renal immunohistochemical staining and Western blotting. RESULTS: The concentrations of atRA in atRA groups were much higher than that in NX and sham groups. Compared to NX, the remnant kidney sclerosis was ameliorated significantly in A1, A2 and A3 groups. The expressions of TGFβ1 decreased parallelized to the levels of glomerulosclerosis. CONCLUSION: atRA has a beneficial effect on retarding the progression of renal fibrosis in the 5/6 nephrectomic rats, possibly through downregulating the glomerular TGFβ1 expression.