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山东大学学报（医学版） ›› 2016, Vol. 54 ›› Issue (2): 1-5.doi: 10.6040/j.issn.1671-7554.0.2015.799

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CCL25/CCR9在大鼠心脏移植慢性排斥反应中的表达及意义

胡连龙,宋光民,赵鑫,白霄,张健,赵廷蕾,王龙   

  1. 山东大学齐鲁医院心脏外科, 山东 济南 250012
  • 收稿日期:2015-08-22 出版日期:2016-02-10 发布日期:2016-02-10
  • 通讯作者: 宋光民. E-mail:songgm@sdu.edu.cn E-mail:songgm@sdu.edu.cn
  • 基金资助:
    山东省科技攻关计划(2010GSF10246);山东省自然科学基金(Y2007C056)

Expression and significance of CCL25/CCR9 in chronic rejection of cardiac allografts in rats

HU Lianlong, SONG Guangmin, ZHAO Xin, BAI Xiao, ZHANG Jian, ZHAO Tinglei, WANG Long   

  1. Department of Cardiovascular Surgery, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China
  • Received:2015-08-22 Online:2016-02-10 Published:2016-02-10

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摘要： 目的 探讨趋化因子25(CCL25)及其趋化因子受体9(CCR9)在大鼠心脏移植慢性排斥反应中的表达及意义。 方法 选取近交系Wistar大鼠为供者,SD大鼠为受者,采用“套管连接技术”行颈部心脏移植术。将受者随机分为3组,每组10只。CsA组:移植术后当日经腹腔注射CsA,10 mg/kg,隔天1次,共10次。CsA+IgG组:CsA应用同 CsA组,同时注射IgG抗体,0.1 mg/kg,隔天1次,共10次。CsA+anti-CCL25组:CsA应用亦同 CsA组,同时注射anti-CCL25中和抗体,0.1 mg/kg,隔天1次,共10次。于术后70 d采集移植心脏,行HE和天狼猩红染色观察各组移植心脏病理学改变,行免疫组化、Western blotting法检测CCL25和CCR9的表达。 结果 CsA组和CsA+IgG组移植心脏的炎症反应、心肌纤维化及心脏移植物血管病程度均较CsA+anti-CCL25组严重(P<0.05);CCL25和CCR9蛋白在大鼠移植心脏中均呈阳性表达;CsA+anti-CCL25组CCL25和CCR9蛋白的表达强度均明显低于CsA组和CsA+IgG组(P<0.05)。 结论 CCL25和CCR9在大鼠心脏移植慢性排斥反应中均有表达,anti-CCL25中和抗体靶向性阻断CCL25/CCR9可减轻移植心脏的慢性排斥反应,表明CCL25/CCR9在大鼠心脏移植慢性排斥反应中具有重要作用。

关键词: 趋化因子受体9, 慢性排斥反应, 心脏移植, 趋化因子25

Abstract: Objective To investigate the expression and significance of CC chemokine ligand 25(CCL25)and CC chemokine receptor 9(CCR9)in chronic rejection of cardiac allografts in rats. Methods Inbred Wistar rats and inbred SD rats were selected as donors and recipients. Cervical heterotopic heart transplantation was performed with “cuff technique”. The recipients were divided into 3 groups randomly, with 10 rats in each group: CsA group, CsA+IgG group, and CsA+anti-CCL25 group. Au vecipients were received 10 mg/kg cyclosporin A(CsA)immediately after the surgery, then once every other day for 10 times. CsA+IgG group was injected with 0.1 mg/kg IgG isotype Ab immediately after the surgery, then once every other day for 10 times. CsA+anti-CCL25 group was injected with 0.1 mg/kg anti-rat CCL25 Ab immediately after the surgery, then once every other day for 10 times. All allografts were harvested on the 70th day postoperatively. HE and sirus red staining were used to observe the pathologic changes of the allograft myocardia. Additionally, immunohistochemistry and Western blotting were adopted to detect the expressions of CCL25 and CCR9 in the myocardium. Results The myocardial inflammatory response, fibrosis and cardiac allograft vasculopathy(CAV)in CsA group and CsA+IgG group were significantly severer than in CsA+anti-CCL25 group(P<0.05); 山 东 大 学 学 报 (医 学 版)54卷2期 -胡连龙,等.CCL25/CCR9在大鼠心脏移植慢性排斥反应中的表达及意义 \=-CCL25 and CCR9 were expressed in the cardiac allografts; the expression of CCL25 and CCR9 in CsA+anti-CCL25 group was significantly lower than that in the other two groups(P<0.05). Conclusion CCL25 and CCR9 are expressed in the chronic rejection of cardiac allografts in rats. Anti-CCL25 Ab can significantly alleviate the pathologic changes of cardiac allografts through targeted blocking of CCL25/CCR9. Our study indicates that CCL25/CCR9 plays important roles in the chronic rejection of cardiac allografts in rats.

Key words: Cardiac transplantation, Chronic rejection, CC chemokine ligand 25, CC chemokine receptor 9

中图分类号: 

  • R737.1
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