摘要：
Objective:To investigate the role of glucose transporter 1 (GLUT1) and sodium-glucose cotransporter 1 ( SGLT1 ) in high glucose dialysate-induced peritoneal fibrosis. Methods:Thirty six male SD rats were randomly divided into 6 groups (6 in each): normal control group, sham operation group, peritoneal dialysis group ( PD group) , PD+phloretin group ( PD+T group) , PD+phlorizin group ( PD+Z group) , PD+ phloretin + phlorizin group ( PD + T + Z group ) . Rat model of uraemia was established using 5/6 nephrotomy, and 2. 5% dextrose peritoneal dialysis solution was used in peritoneal dialysis. Peritoneal equilibration test was performed 24 h after dialysis to evaluate transport function of peritoneum in rats; HE staining was used to observe the morphology of peritoneal tissue; and immunohistochemistry was used to detect the expression of GLUT1 , SGLT1 , TGF-β1 and connective tissue growth factor ( CTGF) in peritoneum. Human peritoneal microvascular endothelial cells ( HPECs ) were divided into 5 groups: normal control group, peritoneal dialysis group ( PD group), PD+phloretin group (PD+T group), PD+phlorezin group (PD+Z group), and PD+phloretin+phlorezin group ( PD+T+Z group) . Real time PCR and Western blotting were used to detect mRNA and protein expressions of GLUT1 , SGLT1 , TGF-β1, CTGF in peritoneal membrane and HPECs. Results:In vivo, compared with sham operation group, rats in PD group had thickened peritoneum, higher ultrafiltration volume, and the mRNA and protein expressions of GLUT1, SGLT1, CTGF, TGF-β1 were significantly increased ( all P <0. 05 ); compared with PD group, thickened peritoneum was attenuated, and the mRNA and protein expressions of GLUT1, SGLT1, CTGF, TGF-β1 were significantly decreased in PD+T, PD+Z and PD+T+Z groups (all P<0. 05). Pearson’s correlation analysis showed that the expressions of GLUT1, SGLT1 in peritoneum were positively correlated with the expressions of TGF-β1 and CTGF (all P<0. 05). In vitro, the mRNA and protein expressions of GLUT1, SGLT1, TGF-β1 , CTGF were significantly increased in HPECs of peritoneal dialysis group ( all P<0. 05), and those in PD+T, PD+Z, and PD+T+Z groups were decreased (all P<0 . 05 ) . Pearson ’ s correlation analysis showed that the expressions of GLUT1 , SGLT1 in HPECs were positively correlated with the expressions of TGF-β1 and CTGF ( all P <0 . 05 ) . Conclusion: High glucose peritoneal dialysis fluid may promote peritoneal fibrosis by upregulating the expressions of GLUT1 and SGLT1 .%目的：：研究葡萄糖转运体1( GLUT1)和钠—葡萄糖转运体1( SGLT1)在腹膜纤维化过程中的作用。方法：体内实验中,取36只SD雄性大鼠随机分为六组：正常对照组、手术对照组、腹膜透析组( PD组)、腹膜透析+根皮素组( PD+T组)、腹膜透析+根皮苷组( PD+Z组)、腹膜透析+根皮素+根皮苷组( PD+T+Z组),每组6只。采用5/6肾脏切除法制作尿毒症模型,腹膜透析采用浓度为2．5%的透析液。停止透析24 h后行腹膜平衡试验评估大鼠腹膜转运功能；HE染色观察壁层腹膜形态；免疫组织化学法检测网膜组织GLUT1、SGLT1、TGF-β1和结缔组织生长因子( CTGF)的表达。体外实验中,体外培养人腹膜微血管内皮细胞( HPEC)并分为五组：正常对照组、腹膜透析组( PD 组)、腹膜透析+根皮素组( PD+T组)、腹膜透析+根皮苷组( PD +Z 组)、腹膜透析+根皮素+根皮苷组( PD+T+Z组)。采用实时定量PCR和蛋白质印迹法检测网膜组织及微血管内皮细胞内GLUT1、SGLT1、TGF-β1、CTGF mRNA及蛋白表达。结果：与手术对照组比较,PD组大鼠的腹膜增厚,超滤量增加,GLUT1、SGLT1、TGF-β1、CTGF mRNA及蛋白均表达上升(均P<0．05)；在使用葡萄糖拮抗剂根皮苷、根皮素后,大鼠腹膜增厚程度减轻, GLUT1、SGLT1、TGF-β1、CTGF mRNA及蛋白表达均下降(均P <0．05)；相关性分析显示,大鼠腹膜GULT1、SGLT1表达与TGF-β1、CTGF表达均呈正相关(均 P <0．05)。2．5%腹膜透析液可以上调人腹膜微血管内皮细胞GLUT1、SGLT1、TGF-β1、CTGF mRNA及蛋白的表达(均P<0．05)；使用葡萄糖拮抗剂后,人腹膜微血管内皮细胞GLUT1、SGLT1、TGF-β1、CTGF mRNA及蛋白表达均下降(均P<0．05)；相关性分析显示,人腹膜微血管内皮细胞GLUT1、SGLT1表达与TGF-β1、CTGF表达均呈正相关(均P<0．05)。结论：高糖腹膜透析液可通过上调GLUT1、SGLT1的表达促进腹膜纤维化。
