褐藻多糖硫酸酯抑制大鼠肾间质纤维化的实验研究

目的观察褐藻多糖硫酸酯（FPS）对慢性肾衰竭大鼠肾间质纤维化及肾小管上皮-间充质细胞转化（EMT）的作用,并探讨该作用与肾组织转化生长因子-β1（TGF-β1）、单核细胞趋化蛋白1（MCP-1）、血小板反应蛋白1（TSP-1）和血管内皮生长因子（VEGF）表达变化的关系。方法将6周龄Wistar雄性大鼠随机分为3组,即正常对照组（n=15）,进食普通饲料;CRF模型组（n=24）,进食含0.75%腺嘌呤的饲料;CRF＋FPS组（n=24）,进食含0.75%腺嘌呤饲料的同时,每天给予FPS200mg/kg灌胃。分别于第2、4、6周末处死大鼠,留取肾组织。采用免疫组化方法检测肾组织肌动蛋白α（α-SMA）的表达,分别采用免疫组化方法和逆转录酶PCR法（RT-PCR）检测肾组织TGF-β1、MCP-1、TSP-1及VEGF的蛋白和mRNA表达情况。结果第2、4、6周时CRF＋FPS组大鼠肾组织α-SMA蛋白表达均明显低于同期CRF模型组（P〈0.05）。CRF＋FPS组大鼠肾组织第2、4周时TGF-β1、MCP-1、TSP-1表达明显低于同期CRF模型组（P〈0.05）,而第2周时TGF-β1、MCP-1、TSP-1的mRNA表达明显低于同期CRF模型组（P〈0.05）,第4周时MCP-1的mRNA表达明显低于同期CRF模型组（P〈0.05）。CRF＋FPS组第2、4周时肾组织VEGF蛋白和mRNA表达明显高于同期CRF模型组（P〈0.05）。结论FPS对慢性肾衰竭大鼠肾小管上皮-间充质细胞转化具有抑制作用,该作用与肾组织TGF-β1、MCP-1及TSP-1的表达下调和VEGF表达上调有关,这可能部分解释FPS的肾保护作用机制。

Mechanism of inhibition of renal tubular epithelial-mesenchymal transition in adenine-induced chronic renal failure rats treated with fucoidan

Objective To observe the effect of fucoidan on renal tubular epithelial- mesenchymal transition (EMT) in adenine-induced chronic renal failure in rats, and examine the relationship between EMT and expressions of transforming growth factor β1 (TGF-β1), monocyte chemoattmctant protein-1 (MCP-1), vascular endothelial growth factor (VEGF) and thrombespondin-1 (TSP-1) in renal tissue. Methods Male Wistar rats were divided into three groups: ①normal group(n=15), ②CRF group(n=24), ③CRF+ FPS group (n=24). CRF rats had free access to diet containing 0.75% adenine. CRF+FPS rats had access to diet containing 0.75% adenine, as well as FPS 200 mg/(kg·d), intragastric administration. All the rats were sacrificed at the end of week 2, 4, 6. Expressions of α-smooth muscle actin (α-SMA),MCP-1, TGF-β1, VEGF and TSP-1 were detected by immunohistological and/or RT-PCR. Results The expressions of α-SMA, MCP-1, TGF-β1 and TSP-1 in renal tissue were significantly lower in CRF+FPS group compared with the CRF group, respectively. Meanwhile VEGF expression in renal tissue was significantly higher in CRF+FPS group than in the CRF rots. Conclusions The inhibitory effect of fucoidan on EMT is probably related to down-regulated expressions of TGF β1, MCP-1 and TSP-1, and up-regulated expression of VEGF. The exact mechanism needs to be studied further.