Ouyang Jun, He Jun, Fan Yi-sun, Fan Cai-bin, Sun He-yun, Wen Duan-gai
Department of Urology, First Affiliated Hospital, Soochow University, Suzhou 215006, China.
Zhonghua Yi Xue Za Zhi. 2010 Mar 16;90(10):698-702.
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.
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 1, 3, 5 and 7 post-transplantation. The serum expressions of IL-15, OPN, PFP and GraB mRNA of recipients were detected by real-time PCR. Allograft tissues were analyzed by pathological assays.
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-15 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 significantly 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.
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.
研究大鼠同种异体肾移植急性排斥反应(AR)早期白细胞介素-15(IL-15)、骨桥蛋白(OPN)、颗粒酶B(GraB)和穿孔素(PFP)mRNA的表达情况。
建立大鼠肾移植模型。以雄性挪威棕色大鼠和Lewis大鼠分别作为供体和受体。分为四组:环孢素A(CsA)组(BN→LEW,n = 10,受体腹腔注射CsA);抗IL-15中和抗体(AB)组(BN→LEW,n = 10,受体腹腔注射抗IL-15中和抗体);AR组(BN→LEW,n = 10,受体腹腔注射生理盐水)和对照组(LEW→LEW,n = 6,受体腹腔注射生理盐水)。于移植后第1、3、5和7天采集受体血样。采用实时荧光定量PCR检测受体血清中IL-15、OPN、PFP和GraB mRNA的表达。对移植肾组织进行病理学检测。
与其他组相比,AR组OPN、IL-15、PFP和GraB mRNA的表达逐渐上调,并于第5天达到峰值。术后第5天,CsA组和AB组IL-15 mRNA的表达分别为9685±1440和4346±741,显著低于AR组(17 022±2153,P<0.01)。AB组IL-15 mRNA的表达显著低于CsA组(P<0.01)。CsA组和AB组OPN mRNA的表达(13 226±1565与19 112±2908)均显著低于AR组(24 663±2449,P<0.01)。但AB组OPN mRNA的表达高于CsA组(P<0.01)。移植后第5天,AB组和CsA组PFP和GraB mRNA的表达均低于AR组(P<0.01)。病理学结果显示,AR组移植后第7天发生严重AR,而AB组排斥反应征象程度减轻。
大鼠同种异体肾移植AR早期,OPN、IL-15、PFP和GraB mRNA的表达上调。在AR早期阻断IL-15/IL-15R通路可下调PFP和GraB mRNA的表达。