CAJ | 학술논문

背景:西罗莫司对肾移植术后急性排斥反应的防治产生重要作用,同时,有研究发现它可抑制血管平滑肌细胞的增殖和迁徙,对慢性排斥反应以及慢性移植肾肾病产生防治作用,但具体的机制尚不清楚.目的:探讨西罗莫司对慢性移植肾肾病肾组织转化生长因子和血管内皮生长因子表达的影响.方法:选择原发性肾病首次尸肾移植者60例,随机分为两组:西罗莫司组和硫唑嘌呤组各30例,分别采用西罗莫司+环孢素A+激素,硫唑嘌呤+环孢素A+激素治疗,西罗莫司首次负荷剂量为6mg,2周内2mg/d,2周后改为1.0～2.0 mg/d,环孢素A为5.0～7.0 mg/d,硫唑嘌呤为50～100 mg/d,激素为15～0 mg/d.术后2年时,对移植肾进行活检.观察移植肾组织转化生长因子β1和血管内皮生长因子表达情况,并观察肝功能、血肌酐浓度、急性排斥反应发生率、人/肾存活率.结果与结论:随访2年,西罗莫司组于术后1,3,12个月的环孢素剂量明显低于硫唑嘌呤组,但是两组之间的血环孢素A的谷值浓度没有明显差异.硫唑嘌呤组中,转化生长因子β1表达主要分布于近曲小管,部分可见肾小球以及间质血管;大部分移植肾组织近曲小管呈阳性表达,线型分布于刷状缘,部分呈阳性表达.部分患者肾小球脏层上皮细胞呈节段性阳性表达.内皮细胞及系膜偶见阳性表达.西罗莫司组中,转化生长因子β1在近曲小管的表达则明显减弱,肾小球和间质血管无明显改变.硫唑嘌呤组中血管内皮生长因子表达主要见于肾小球脏层上皮细胞,部分病例也可见于内皮细胞及系膜细胞,间质血管呈阳性表达,主要分布于内皮层.西罗莫司组,肾小球、间质血管染色均明显减少.与硫唑嘌呤组比较,西罗莫司组人/肾存活率高、移植肾组织转化生长因子β1和血管内皮生长因子表达明显降低.结果表明,西罗莫司可降低移植肾组织转化生长因子β1和血管内皮生长因子表达,减缓慢性移植肾肾病的进展,延长移植肾存活时间. 揹景:西囉莫司對腎移植術後急性排斥反應的防治產生重要作用,同時,有研究髮現它可抑製血管平滑肌細胞的增殖和遷徙,對慢性排斥反應以及慢性移植腎腎病產生防治作用,但具體的機製尚不清楚.目的:探討西囉莫司對慢性移植腎腎病腎組織轉化生長因子和血管內皮生長因子錶達的影響.方法:選擇原髮性腎病首次尸腎移植者60例,隨機分為兩組:西囉莫司組和硫唑嘌呤組各30例,分彆採用西囉莫司+環孢素A+激素,硫唑嘌呤+環孢素A+激素治療,西囉莫司首次負荷劑量為6mg,2週內2mg/d,2週後改為1.0～2.0 mg/d,環孢素A為5.0～7.0 mg/d,硫唑嘌呤為50～100 mg/d,激素為15～0 mg/d.術後2年時,對移植腎進行活檢.觀察移植腎組織轉化生長因子β1和血管內皮生長因子錶達情況,併觀察肝功能、血肌酐濃度、急性排斥反應髮生率、人/腎存活率.結果與結論:隨訪2年,西囉莫司組于術後1,3,12箇月的環孢素劑量明顯低于硫唑嘌呤組,但是兩組之間的血環孢素A的穀值濃度沒有明顯差異.硫唑嘌呤組中,轉化生長因子β1錶達主要分佈于近麯小管,部分可見腎小毬以及間質血管;大部分移植腎組織近麯小管呈暘性錶達,線型分佈于刷狀緣,部分呈暘性錶達.部分患者腎小毬髒層上皮細胞呈節段性暘性錶達.內皮細胞及繫膜偶見暘性錶達.西囉莫司組中,轉化生長因子β1在近麯小管的錶達則明顯減弱,腎小毬和間質血管無明顯改變.硫唑嘌呤組中血管內皮生長因子錶達主要見于腎小毬髒層上皮細胞,部分病例也可見于內皮細胞及繫膜細胞,間質血管呈暘性錶達,主要分佈于內皮層.西囉莫司組,腎小毬、間質血管染色均明顯減少.與硫唑嘌呤組比較,西囉莫司組人/腎存活率高、移植腎組織轉化生長因子β1和血管內皮生長因子錶達明顯降低.結果錶明,西囉莫司可降低移植腎組織轉化生長因子β1和血管內皮生長因子錶達,減緩慢性移植腎腎病的進展,延長移植腎存活時間.
배경:서라막사대신이식술후급성배척반응적방치산생중요작용,동시,유연구발현타가억제혈관평활기세포적증식화천사,대만성배척반응이급만성이식신신병산생방치작용,단구체적궤제상불청초.목적:탐토서라막사대만성이식신신병신조직전화생장인자화혈관내피생장인자표체적영향.방법:선택원발성신병수차시신이식자60례,수궤분위량조:서라막사조화류서표령조각30례,분별채용서라막사+배포소A+격소,류서표령+배포소A+격소치료,서라막사수차부하제량위6mg,2주내2mg/d,2주후개위1.0～2.0 mg/d,배포소A위5.0～7.0 mg/d,류서표령위50～100 mg/d,격소위15～0 mg/d.술후2년시,대이식신진행활검.관찰이식신조직전화생장인자β1화혈관내피생장인자표체정황,병관찰간공능、혈기항농도、급성배척반응발생솔、인/신존활솔.결과여결론:수방2년,서라막사조우술후1,3,12개월적배포소제량명현저우류서표령조,단시량조지간적혈배포소A적곡치농도몰유명현차이.류서표령조중,전화생장인자β1표체주요분포우근곡소관,부분가견신소구이급간질혈관;대부분이식신조직근곡소관정양성표체,선형분포우쇄상연,부분정양성표체.부분환자신소구장층상피세포정절단성양성표체.내피세포급계막우견양성표체.서라막사조중,전화생장인자β1재근곡소관적표체칙명현감약,신소구화간질혈관무명현개변.류서표령조중혈관내피생장인자표체주요견우신소구장층상피세포,부분병례야가견우내피세포급계막세포,간질혈관정양성표체,주요분포우내피층.서라막사조,신소구、간질혈관염색균명현감소.여류서표령조비교,서라막사조인/신존활솔고、이식신조직전화생장인자β1화혈관내피생장인자표체명현강저.결과표명,서라막사가강저이식신조직전화생장인자β1화혈관내피생장인자표체,감완만성이식신신병적진전,연장이식신존활시간.
BACKGROUND: Sirolimus (SRL) has a very important effect on preventing and treating acute rejection in renal transplantation. Moreover, it is a potent inhibitor of smooth muscle cell proliferation and migration, and may play a role in preventing chronic rejection and chronic allograft nephropathy. However, the precise mechanism remains unclear. OBJECTIVE: To explore the influence of SRL on transforming growth factor-beta 1 (TFG-β1) and vascular endothelial growth factor (VEGF) expression in chronic allograft nephropathy. METHODS: A total of 60 renal allograft recipients were randomly divided into SRL group, treated by SRL+ cyclosporine A (CsA) +prednisone (Pred), and Azathioprine (Aza) group, treated by Aza +CsA+Pred. SRL was 6 mg and 2 mg per day in 2 weeks, and changed to 1.0-2.0 mg per day after 2 weeks; CsA was 5.0-7.0 mg per day; Aza was 50-100 mg per day, and Pred was 15-20 mg per day. After two years, the pathological changes of the allografts, serum creatinine of the recipients, distribution of TGF-β1 and VEGF, and hepatic function were observed. RESULTS AND CONCLUSION: The patients were followed-up for 2 years. CsA dose was significantly lower in SRL group than Aza group at 1, 3, 12 months postoperatively, but there were no differences in blood plasma CsA C_0 concentration between two groups. In Aza group, TFG-β1 was expressed mostly in proximal convoluted tubule, also in glomerulus and interstitial blood vessel. Majority of tissues expressed TFG-β1 in proximal convoluted tubule, and presented at brush border in line. Some tissues expressed TFG-β1 in glomerular splanchnoderm epithelial cells. Additionally, little TFG-β1 was observed in endothelial cells and intercapillary cells. In SRL group, there was significant decreasing staining in proximal convoluted tubule, but there were no differences in glomerulus and blood vessel. In Aza-group, VEGF was expressed mostly in glomerular splanchnoderm epithelial cells, and some in endothelial cells and intercapillary cells. VEGF was positively expressed in interstitial vessel, especially in endothelial layer. There was significant decreasing staining in SRL group glomerulus and blood vessel. Compared with Aza group, patient/kidney survival was high, but VEGF and TFG-β1 expression was significantly decreased. Results from the study showed that SRL decreased VEGF and TFG-β1 expression in renal graft, delayed progression of chronic allograft nephropathy, and prolonged survival of allografts.