CAJ | 학술논문

目的探讨血管内皮生长因子(VEGF)在慢性移植肾肾病(CAN)早期病变中的作用及其机理.方法依照标准的大鼠CAN模型进行大鼠左肾原位肾移植,供鼠为F344大鼠,受鼠为Lewis大鼠,术后10d切除受鼠自体右肾.供、受鼠对照组分别为单纯右肾切除的F344大鼠和Lewis大鼠.分别于术后4、8和12周时,获取各组大鼠的尿液、外周血和肾组织样本,检测24 h尿蛋白、尿肌酐及血肌酐水平,采用免疫组织化学法检测肾组织中VEGF和整合素连接酶(ILK)的表达水平.结果移植组大鼠在术后4周时肾间质可见单个核细胞浸润,12周时可见血管平滑肌细胞的移行与增殖,移植组各时点ILK和VEGF表达水平显著高于同时点的供、受鼠对照组(P＜0.05),移植组大鼠VEGF表达水平与24 h尿蛋白定量、血清肌酐水平、肾间质单个核细胞浸润、肾小动脉血管平滑肌细胞数量呈显著正相关,相关系数(r)分别为0.713 (P＜0.05)、0.534(P＜0.01)、0.845 (P＜0.01)、0.539(P＜0.01)、0.506(P＜0.01).肾小管间质及肾小动脉中VEGF与ILK表达水平呈显著正相关(r=0.446,P＜0.01).结论 VEGF表达上调在大鼠CAN早期病理变化中起到重要作用,移植肾肾小管间质及肾小动脉中VGEF表达上调与ILK的作用机制相关.
목적 탐토혈관내피생장인자(VEGF)재만성이식신신병(CAN)조기병변중적작용급기궤리.방법 의조표준적대서CAN모형진행대서좌신원위신이식,공서위F344대서,수서위Lewis대서,술후10d절제수서자체우신.공、수서대조조분별위단순우신절제적F344대서화Lewis대서.분별우술후4、8화12주시,획취각조대서적뇨액、외주혈화신조직양본,검측24 h뇨단백、뇨기항급혈기항수평,채용면역조직화학법검측신조직중VEGF화정합소련접매(ILK)적표체수평.결과 이식조대서재술후4주시신간질가견단개핵세포침윤,12주시가견혈관평활기세포적이행여증식,이식조각시점ILK화VEGF표체수평현저고우동시점적공、수서대조조(P＜0.05),이식조대서VEGF표체수평여24 h뇨단백정량、혈청기항수평、신간질단개핵세포침윤、신소동맥혈관평활기세포수량정현저정상관,상관계수(r)분별위0.713 (P＜0.05)、0.534(P＜0.01)、0.845 (P＜0.01)、0.539(P＜0.01)、0.506(P＜0.01).신소관간질급신소동맥중VEGF여ILK표체수평정현저정상관(r=0.446,P＜0.01).결론 VEGF표체상조재대서CAN조기병리변화중기도중요작용,이식신신소관간질급신소동맥중VGEF표체상조여ILK적작용궤제상관.
Objective To investigate the role of vascular endothelial growth factor (VEGF) in rats with chronic allograft nephropathy (CAN) at early stage.Method The left donor kidneys from Fisher(F344) rats were orthotopically transplanted into Lewis(LEW) recipients.Meanwhile,the F344 rats and LEW rats subject to right nephrectomy served as control groups.The urine,peripheral blood and renal tissues were harvested respectively at the 4th,8th,and 12th week after transplantation.The creatinine clearance rate (CCr) was calculated by urine creatinine of 24 h urine.The level of 24 h urine protein was determined.The serum creatinine level was measured.The expression of VEGF and integrin-linked kinase (ILK) was detected by using immunohistochemistry.Results Infiltration of mononuclear cells in allografts was markedly aggravated as compared with the controls at the 4th week after transplantation.Allografts got severe interstitial fibrosis and tubular atrophy at the 12 th week after transplantation.The expression of VEGF and ILK was up-regulated in the kidney of CAN rats after transplantation as the time went on.The expression of VEGF was significantly correlated with 24 h urine protein excretion (r=0.713,P＜0.05),serum creatinine levels (r=0.534,P＜0.01),the number of tubulointerstitial infiltrated mononuclear cells (r =0.845,P＜0.01),the number of smooth muscle cells in vascular wall (r =0.539,P＜0.01),and the extent of interstitial fibrosis (r =0.506,P ＜0.01).There was a significantly positive correlation between VEGF and ILK in CAN rats after transplantation (r =0.446,P＜ 0.01).Conclusion VEGF might play an key role in CAN at early stage,and the up-regulated VEGF in the tubulointerstitium and vascular wall is correlated with the role of ILK in the CAN.