中华眼科杂志
中華眼科雜誌
중화안과잡지
Chinese Journal of Ophthalmology
2009年
8期
742-745
,共4页
脉络膜新生血管化%苯脲化合物%受体%白细胞介素8B%大鼠
脈絡膜新生血管化%苯脲化閤物%受體%白細胞介素8B%大鼠
맥락막신생혈관화%분뇨화합물%수체%백세포개소8B%대서
Choroidal neovaacularization%Phenylurea compounds%Receptors%interleukin-SB%Rats
目的 观察CXC趋化因子受体2(CXCR2)的选择性非肽类抑制剂SB225002对大鼠脉络膜新生血管形成的抑制作用.方法 实验研究.使用激光对12只棕色挪威大鼠诱导脉络膜新生血管(CNV),6只光凝术后立即玻璃体腔注射10μmol/L的SB225002,6只给予二甲基亚砜作为对照.3只大鼠未给予激光光凝及眼内注射,作为阴性对照用于定量实时逆转录聚合酶链反应(qRTPCR)检查.光凝术后7 d,采用荧光素眼底血管造影分析CNV损伤荧光素渗漏的变化,脉络膜铺片定量分析CNV面积的变化,qRT-PeR观察视网膜色素上皮一脉络膜复合物CXCR2和血管内皮生长因子(VEGF)mRNA表达水平的变化.荧光素眼底血管造影图像的渗漏评分比较采用Mann-Whitney检验;CNV面积比较采用配对t检验;CXCR2或VEGF的mRNA水平比较采用Wilcoxon检验.结果 10μmol/L的SB225002能有效抑制CNV损伤造成的荧光素渗漏.光凝术后7 d 10μmol/L的SB225002组脉络膜铺片的CNV面积为(10531 4±4627)μm2,DMSO组为(30974±6762)μm2,10μmol/L的SB225002组面积较DMSO组缩小66%(t=2.54,P=0.001).10μmoL/L SB225002组CXCR2 mRNA和VEGF mRNA相对值分别为1.22 4±0.92和1.93±0.87,与DMSO组的差异具有统计学意义(t=8.54,3.61;P=0.007,0.002).结论 SB225002在CNV形成早期通过阻断IL-8与CXCR2的结合,能够有效抑制血管的新生,提示治疗CNV的一个新的化疗干预机制.
目的 觀察CXC趨化因子受體2(CXCR2)的選擇性非肽類抑製劑SB225002對大鼠脈絡膜新生血管形成的抑製作用.方法 實驗研究.使用激光對12隻棕色挪威大鼠誘導脈絡膜新生血管(CNV),6隻光凝術後立即玻璃體腔註射10μmol/L的SB225002,6隻給予二甲基亞砜作為對照.3隻大鼠未給予激光光凝及眼內註射,作為陰性對照用于定量實時逆轉錄聚閤酶鏈反應(qRTPCR)檢查.光凝術後7 d,採用熒光素眼底血管造影分析CNV損傷熒光素滲漏的變化,脈絡膜鋪片定量分析CNV麵積的變化,qRT-PeR觀察視網膜色素上皮一脈絡膜複閤物CXCR2和血管內皮生長因子(VEGF)mRNA錶達水平的變化.熒光素眼底血管造影圖像的滲漏評分比較採用Mann-Whitney檢驗;CNV麵積比較採用配對t檢驗;CXCR2或VEGF的mRNA水平比較採用Wilcoxon檢驗.結果 10μmol/L的SB225002能有效抑製CNV損傷造成的熒光素滲漏.光凝術後7 d 10μmol/L的SB225002組脈絡膜鋪片的CNV麵積為(10531 4±4627)μm2,DMSO組為(30974±6762)μm2,10μmol/L的SB225002組麵積較DMSO組縮小66%(t=2.54,P=0.001).10μmoL/L SB225002組CXCR2 mRNA和VEGF mRNA相對值分彆為1.22 4±0.92和1.93±0.87,與DMSO組的差異具有統計學意義(t=8.54,3.61;P=0.007,0.002).結論 SB225002在CNV形成早期通過阻斷IL-8與CXCR2的結閤,能夠有效抑製血管的新生,提示治療CNV的一箇新的化療榦預機製.
목적 관찰CXC추화인자수체2(CXCR2)적선택성비태류억제제SB225002대대서맥락막신생혈관형성적억제작용.방법 실험연구.사용격광대12지종색나위대서유도맥락막신생혈관(CNV),6지광응술후립즉파리체강주사10μmol/L적SB225002,6지급여이갑기아풍작위대조.3지대서미급여격광광응급안내주사,작위음성대조용우정량실시역전록취합매련반응(qRTPCR)검사.광응술후7 d,채용형광소안저혈관조영분석CNV손상형광소삼루적변화,맥락막포편정량분석CNV면적적변화,qRT-PeR관찰시망막색소상피일맥락막복합물CXCR2화혈관내피생장인자(VEGF)mRNA표체수평적변화.형광소안저혈관조영도상적삼루평분비교채용Mann-Whitney검험;CNV면적비교채용배대t검험;CXCR2혹VEGF적mRNA수평비교채용Wilcoxon검험.결과 10μmol/L적SB225002능유효억제CNV손상조성적형광소삼루.광응술후7 d 10μmol/L적SB225002조맥락막포편적CNV면적위(10531 4±4627)μm2,DMSO조위(30974±6762)μm2,10μmol/L적SB225002조면적교DMSO조축소66%(t=2.54,P=0.001).10μmoL/L SB225002조CXCR2 mRNA화VEGF mRNA상대치분별위1.22 4±0.92화1.93±0.87,여DMSO조적차이구유통계학의의(t=8.54,3.61;P=0.007,0.002).결론 SB225002재CNV형성조기통과조단IL-8여CXCR2적결합,능구유효억제혈관적신생,제시치료CNV적일개신적화료간예궤제.
Objective We tested the applicability of using SB225002,a selective non-peptide CXCR2 inhibitor,for inhibiting experimental chomidal neovascularization(CNV)in Brown Norway(BN)rats.Methods It was an experimental study.CNV was induced in 12 aduh BN rots with laser photocoagulation.10μmol/L SB225002 was administered into the vitreous of 6 rats right after Jaser injury.DMSO was used as the control in other 6 rats.Three BN rats were served as non-laser-treated controls in quantitative real-time reverse transcription PCR(qRT-PCR)analysis.Fluorescein angiography was performed on day 7 postoperatively to observe the fluorescein leakage of CNV.Quantitative analysis on choroidal flat mounts was performed to evaluate the area changes of CNV lesions.qRT-PCR analysis was used to compare the changes shown by the SB225002-,DMSO-and non-laser-treated BN rats with regard to mRNA levels of CXCR2 and vascular endothelial growth factor(VEGF)in the RPE-choroidal complex.Results SB225002(10μmol/L)significantly inhibited the fluorescein leakage(P＜0.05),the extent of neovascularization on choroidal flat mount of rat CNV model was decreased up to 66%(t=2.54,P=0.001).CXCR2 and VEGF mRNA were reduced significantly following this treatment(t=8.54,3.61;P=0.007,0.002).Conclusion SB225002 inhibits angiogenic activity of IL-8 by blocking its binding with CXCR2 in the early stage of CNV,which may provide a potential new therapeutic strategy for CNV.
