CAJ | 학술논문

目的研究白细胞介素(IL)15、骨桥蛋白、穿孔素及颗粒酶B在大鼠肾脏移植急性排斥反应(AR)早期的表达变化.方法以BN大鼠和LEW大鼠分别作为供受体,建立大鼠肾移植动物模型.环孢素A处理组(CsA组):(BN→LEW,术后注射环孢素A);IL-15阻断组:(BN→LEW,术后注射IL-15抗体);AR组:(BN→LEW,术后注射生理盐水);对照组:(LEW→LEW,术后注射生理盐水).对照组6只大鼠,其余组10只大鼠,于移植后1、3、5、7 d取外周血,逆转录一聚合酶链反应(RT-PCR)动态检测骨桥蛋白、IL-15、穿孔素及颗粒酶B mRNA的表达,并作移植肾病理分析.结果 AR组、CsA组及IL-15阻断组肾移植术后IL-15、骨桥蛋白mRNA表达逐渐上调,第5天均达到高峰;对照组均处于低水平.术后第5天,CsA组和IL-15阻断组IL-15 mRNA分别为9685±1440、4346±741均低于AR组(17 022±2153,P<0.01),IL-15阻断组明显低于CsA组(P<0.01);CsA组和IL-15阻断组骨桥蛋白mRNA分别为13 226±1565、19 112±2908均低于AR组(24 663±2449,P<0.01),IL-15阻断组明显高于CsA组(P<0.01).术后第5天IL-15阻断组和CsA组穿孔素和颗粒酶B mRNA表达明显低于AR组(P<0.01).移植肾病理组织检查显示,AR组呈现重度急性排斥反应,IL-15阻断组排斥反应征象轻微.结论大鼠肾移植AR发生早期骨桥蛋白、IL-15、穿孔素和颗粒酶B mRNA在外周血中均高水平表达,通过阻断IL-15/IL-15受体途径可明显下调颗粒酶B和穿孔素mRNA的表达.
목적 연구백세포개소(IL)15、골교단백、천공소급과립매B재대서신장이식급성배척반응(AR)조기적표체변화.방법 이BN대서화LEW대서분별작위공수체,건립대서신이식동물모형.배포소A처리조(CsA조):(BN→LEW,술후주사배포소A);IL-15조단조:(BN→LEW,술후주사IL-15항체);AR조:(BN→LEW,술후주사생리염수);대조조:(LEW→LEW,술후주사생리염수).대조조6지대서,기여조10지대서,우이식후1、3、5、7 d취외주혈,역전록일취합매련반응(RT-PCR)동태검측골교단백、IL-15、천공소급과립매B mRNA적표체,병작이식신병리분석.결과 AR조、CsA조급IL-15조단조신이식술후IL-15、골교단백mRNA표체축점상조,제5천균체도고봉;대조조균처우저수평.술후제5천,CsA조화IL-15조단조IL-15 mRNA분별위9685±1440、4346±741균저우AR조(17 022±2153,P<0.01),IL-15조단조명현저우CsA조(P<0.01);CsA조화IL-15조단조골교단백mRNA분별위13 226±1565、19 112±2908균저우AR조(24 663±2449,P<0.01),IL-15조단조명현고우CsA조(P<0.01).술후제5천IL-15조단조화CsA조천공소화과립매B mRNA표체명현저우AR조(P<0.01).이식신병리조직검사현시,AR조정현중도급성배척반응,IL-15조단조배척반응정상경미.결론 대서신이식AR발생조기골교단백、IL-15、천공소화과립매B mRNA재외주혈중균고수평표체,통과조단IL-15/IL-15수체도경가명현하조과립매B화천공소mRNA적표체.
Objective To study the expressions of interleukin-15(IL-15),osteopontin(OPN), granzyme B(GraB)and perforin (PFP) mRNA in early stage of acute rejection (AR) of renal allograft in rats.Methods The rat renal transplantation model was established.Male Brown Norway and Lewis rats were used as donors and recipients.Four groups were designated:CsA group(BN→LEW,n=10, recipients were treated with CsA i.P.):AB group(BN→LEW,n=10,recipients were treated with anti-IL-15 neutralizing antibody i.P.):AR group(BN→LEW,n=10,recipients were treated with normal saline i.P.)and control group(LEW→LEW,n=6,recipients were treated with normal saline i.P.).The blood samples of recipients were drawn at Days l,3,5 and 7 post-transplantation.The serum expressions ot IL-15.OPN,PFP and GraB mRNA of recipients were detected by real-time PCR.AIIograft tissues were analyzed by pathological assays.Results In comparison with other groups,the expressions of OPN,IL-15, PFP and GraB mRNA in AR group were gradually up.regulated and peaked at Day 5.The expressions of IL-l5 mRNA in CsA and AB groups were 9685±1440 and 4346±741 respectively at Day 5 post-operation. It was significantly lower than that in AR group(17 022±2153,P<0.01).The expression of IL-15 mRNA in AB group was signiflcantly lower than that in CsA group(P<0.01).The expressions of OPN mRNA in CsA and AB groups(13 226±1565 vs 19 112 ±2908)were both significantly lower than that in AR group (24 663±2449.P<0.01).But the expression of OPN mRNA in AB group was higher than that in CsA group(P<0.01).At Day 5 post-transplantation,both the expressions of PFP and GraB mRNA in AB and CsA groups was lower than that in AR group(P<0.01).The pathological results showed that severe AR occurred at Day 7 post-transplantation in AR group and whereas the extent of rejection sign relieved in AB group.Conclusion In early stage of AR of renal allograft in rats,the expressions of OPN,IL-15,PFP and GraB mRNA are up-regulated.Blocking IL-15/IL-15R pathway in early stage of AR can down-regulate the expressions of PFP and GraB mRNA.