高糖及洛沙坦对人腹膜间皮细胞Smad表达的影响  

Effects of high glucose and losartan on the expression of Smad in human peritoneal mesothelial cells

作　　者：姚强[1] 钱家麒[1] 林星辉[1] 

机构地区：[1]上海第二医科大学附属仁济医院肾脏科,200001

出　　处：《中华肾脏病杂志》2004年第6期396-399,共4页Chinese Journal of Nephrology

摘　　要：目的 探讨腹膜纤维化机制以及可能的防治措施。方法从网膜获取腹膜间皮细胞,分别用不同浓度葡萄糖或甘露醇的培养液或同时加入4.25％,葡萄糖和含洛沙坦(losartan)的培养液刺激,检测转化生长因子β1(TGF-β1)及Smad的表达。结果 (1)高糖上调人腹膜间皮细胞Smad 2和Smad 4基因表达;Smad 3表达无变化;(2)高渗对Smad家族和TGF-β1的表达没有影响;(3)洛沙坦抑制Smad 2基因的表达,但对蛋白质无抑制作用;(4)高糖刺激问皮细胞TGF-β1的表达,其表达量在加入洛沙坦后明显下降。结论高糖刺激了TGF-β1和Smad 2、Smad 4的表达,这可能是细胞外基质堆积、腹膜纤维化的机制之一。洛沙坦可通过下调TGF-β1,抑制Smad 2基因表达。Objective To investigate if the mechanism of high glucose and losartan in mediating the expression of Smad in human peritoneal mesothelial cells (HPMC) and the possible management of HPMC. Methods Peritoneum was obtained from patients undergoing elective abdominal surgery. HPMCs were incubated in medium containing different concentrations of dextrose, mannitol (1. 5%, 2. 5% , 4. 25% ) and combination with dextrose and losartan. TGF-β1 in supernatant was detected by ELISA and HPMCs were collected to examine Smad family expression with RT-PCR and Western Blot. Results (1) High glucose up-regulated the expression of Smad 2 at both gene and protein levels, especially in 2. 5% and 4. 25% dextrose groups (P < 0. 05). It also slightly elevated the expression of Smad 4 in 4. 25% dextrose group. However, the expression of Smad 3 was not affected. (2)High osmolarity was not involved in TGF-β1-Smad signaling pathway. (3)Losartan inhibited the expression of Smad 2 on gene level but not on protein level. (4) High glucose up-regulated the levels of TGF-β1 in a dose- dependent manner which was markedly inhibited by losartan. Conclusions High glucose can up-regulate the expression of TGF-β1, Smad 2 and Smad 4, which may be involved in the mechanism of peritoneal fibrosis. Losartan can decrease the concentration of TGF-β1 and expression of Smad 2 on gene level, which may be beneficial to the prevention and treatment of peritoneal fibrosis in long-term peritoneal dialysis patients.

关 键 词：表达量 洛沙坦 TGF-β1 SMAD2 人腹膜间皮细胞 高糖 腹膜纤维化 SMAD4基因 蛋白质 培养液 

分 类 号：R363[医药卫生—病理学]