摘要
目的探讨环氧化酶2（COX-2）抑制剂（塞来昔布）对尿毒症腹膜透析（PD）大鼠腹膜血管新生及腹膜功能的影响。方法清洁级SD雄性大鼠被随机分为5组：正常对照组（11=8）、假手术组（11=8）、尿毒症组（n=8）、4．25％透析液透析组[PD组，又随机分为2周组（PD2周组，n=8）和4周组（PD4周组，n=8）1及PD＋塞来昔布干预组（n=8）。从腹膜结构、功能、腹膜组织毛细血管密度（MVD）及COX-2、血管内皮生长因子（VEGF）表达4个方面，来观察塞来昔布对尿毒症腹膜透析大鼠腹膜血管新生及腹膜功能的影响。结果随着腹膜透析的进行，大鼠腹膜厚度增加，炎性细胞浸润明显，腹膜平衡实验（PET）显示超滤量明显下降，葡萄糖转运量上升（均P〈0．05），而塞来昔布干预可提高净超滤量，减少葡萄糖转运量（均P〈0．05）。尿毒症组和PD组腹膜组织MVD及COX-2、VEGF表达均显著高于正常对照组（均P〈0．05）；而PD＋塞来昔布干预组MVD及COX-2、VEGF表达均显著低于尿毒症组（均P〈0．05）。相关性分析显示，COX-2表达量与MVD、VEGF表达量均呈正相关（P〈0．05），VEGF表达量与MVD呈正相关（P〈0．05）。结论体内高糖透析液与尿毒症环境的刺激可以促使腹膜组织COX-2、VEGF表达上调及毛细血管生成增多。塞来昔布可缓解长期PD导致的腹膜组织形态结构和功能的改变。塞来昔布可以抑制尿毒症PD大鼠腹膜新生血管的形成，可能是通过抑制COX-2的表达来减少VEGF的产生而发挥作用的。
Objective To investigate the effects of the cyclooxygenase-2 （COX-2） inhibitor （celecoxih） on angiogenesis and peritoneal function of uremic peritoneal dialysis rats. Methods Forty- eight male SD rats were selected, and they were randomly divided into five groups： normal control group（n = 8）, sham operation group（n = 8）, uremia group（5/6 nephrectomy, n = 8）, PD group [4.25% PD solution, 2 weeks PD model（n = 8） and 4 weeks PD model（n = 8）], PD ＋ celecoxib intervention group[treated by eelecoxib（20 mg/kg） via oral garage, n = 8].The peritoneum of uremic peritoneal dialysis rats was observed in different dialysis time from peritoneal structures, functions, peritoneal tissue capillary density （microvessel density, MVD） and COX-2, vascular endothelial growth factor （VEGF） expression level, and the impacts of celecoxih on uremic peritoneal dialysis ratsperitoneal angiogenesis and peritoneal function were study. Results With the conduct of the peritoneal dialysis, peritoneal thickness increased, the inflammatory cells infiltrated, peritoneal equilibration test （PET） showed that uhrafiltration volume decreased significantly （P 〈 0.05）, the amount of glucose transport rate rised significantly （P 〈 0.05）, but the celecoxib could improve net ultrafiltration volume （P 〈 0.05）, and reduce the glucose transport rate （P 〈 0.05）. The peritoneal tissue MVD and COX- 2, VEGF expression were significantly increased in uremia group and PD group compared with that in the normal control group （all P 〈 0.05）, were significantly lower in PD ＋ Celecoxib intervention group than that in uremia group （P 〈 0.05）. The correlation analysis showed that the level of COX-2 protein expression with MVD, VEGF protein expression was positively correlated （both P 〈 0.05）, the level of VEGF protein expression and MVD was positively correlated （P 〈 0.05）. Conclusions In vivo high glucose dialysate and uremia environmental can stimulate the COX-2 and VEGF expression raised, and the capillaries production increased in peritoneal tissue. Celecoxib can alleviate the change of peritoneal tissue morphology and function in long-term peritoneal dialysis rats. Celecoxib inhibits the peritoneal neovascularization of uremic peritoneal dialysis rats, possibly through inhibition of COX-2 expression to reduce the production of VEGF.
出处
《中华肾脏病杂志》
CAS
CSCD
北大核心
2013年第6期449-453,共5页
Chinese Journal of Nephrology
基金
河南省科技厅攻关项目（112300410317）
关键词
腹膜透析
尿毒症
环氧化酶2抑制剂
塞来昔布
血管内皮生长因子
血管新生
腹膜功能
Peritoneal dialysis
Uremia
Cyclooxygenase 2 inhibitors
Celecoxib
Vascular endothelial growth factor
Angiogenesis
Peritoneal function
