CAJ | 학술논문

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(n=8)、假手术组(n=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(PD 4周组,n=8)]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.
목적 탐토배양화매2(COX-2)억제제(새래석포)대뇨독증복막투석(PD)대서복막혈관신생급복막공능적영향.방법 청길급SD웅성대서피수궤분위5조:정상대조조(n=8)、가수술조(n=8)、뇨독증조(n=8)、4.25％투석액투석조[PD조,우수궤분위2주조(PD2주조,n=8)화4주조(PD 4주조,n=8)]급PD+새래석포간예조(n=8).종복막결구、공능、복막조직모세혈관밀도(MVD)급COX-2、혈관내피생장인자(VEGF)표체4개방면,래관찰새래석포대뇨독증복막투석대서복막혈관신생급복막공능적영향.결과 수착복막투석적진행,대서복막후도증가,염성세포침윤명현,복막평형실험(PET)현시초려량명현하강,포도당전운량상승(균P＜ 0.05),이새래석포간예가제고정초려량,감소포도당전운량(균P＜ 0.05).뇨독증조화PD조복막조직MVD급COX-2、VEGF표체균현저고우정상대조조(균P＜ 0.05)；이PD+새래석포간예조MVD급COX-2、VEGF표체균현저저우뇨독증조(균P＜0.05).상관성분석현시,COX-2표체량여MVD、VEGF표체량균정정상관(P＜0.05),VEGF표체량여MVD정정상관(P＜0.05).결론 체내고당투석액여뇨독증배경적자격가이촉사복막조직COX-2、VEGF표체상조급모세혈관생성증다.새래석포가완해장기PD도치적복막조직형태결구화공능적개변.새래석포가이억제뇨독증PD대서복막신생혈관적형성,가능시통과억제COX-2적표체래감소VEGF적산생이발휘작용적.
Objective To investigate the effects of the cyclooxygenase-2 (COX-2) inhibitor (celecoxib) 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 celecoxib(20 mg/kg) via oral gavage,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 celecoxib on uremic peritoneal dialysis rats peritoneal 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 ultrafiltration 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.