巴利昔单抗预处理抑制T淋巴细胞增殖对小鼠肾脏缺血再灌注损伤的保护作用  

Preconditioning with basiliximab protects renal ischemia/reperfusion injury by inhibiting T lympho-cytes proliferation

作　　者：吕中桥 范钰[2] 张艳涛[1] 邱镇[1] 胡建鹏[1] 崔飞伦[1] 王全兴[3] 

机构地区：[1]江苏大学附属人民医院泌尿外科,江苏镇江212002 [2]江苏大学附属人民医院肿瘤研究所,江苏镇江212002 [3]第二军医大学免疫学研究所

出　　处：《中华实验外科杂志》2014年第6期1210-1212,F0003,共4页Chinese Journal of Experimental Surgery

摘　　要：目的探讨巴利昔单抗（Basiliximab）预处理对小鼠。肾脏缺血再灌注损伤（IRI）的影响及其机制。方法将54只健康雄性C57BL／6小鼠随机分为3组（n=18）。假手术组（Sham组）：仅行开腹及双侧肾蒂分离；缺血再灌注对照组（IR组）：术前30min经尾静脉注射非特异性IgG（1mg／kg）后，夹闭双肾蒂45min；巴利昔单抗组（Basiliximab组）：术前30min经尾静脉注射巴利昔单抗（1m/kg）后，夹闭双肾蒂45min。各组小鼠于再灌注1、4、24h后取其血、尿液检测血肌酐（Scr）、血尿素氮（BUN）、肾小球滤过钠排泄分数（FENa，％）；取肾组织行病理学检查；流式细胞仪检测小鼠肾脏中CIM^＋T淋巴细胞及CD8^＋T淋巴细胞含量；逆转录-聚合酶链反应（RT—PCR）检测白细胞介素（IL）-2、肿瘤坏死因子-α（TNF-α）、IL-6表达量。结果与Sham组比较，再灌注24h后，小鼠血清Scr、BUN水平在IR组[（174．33±7．69）、（69．90±1．68）μmol／L]和Basiliximab组[（51．67±6．56）、（23．97±2．12）μmol／L]明显升高（P〈0．05）；FENa明显升高（P〈0．05）；。肾组织损伤及评分均升高（P〈0．05），肾组织内IL-2、TNF—α、IL-6表达量升高（P〈0．05）；与Sham组比较，再灌注4h后，小鼠肾脏CIM^＋T淋巴细胞含量在IR组和Basiliximab组均升高（P〈0．05）。其中上述指标在Basiliximab组水平较IR组均明显降低（P〈0．05）。结论巴利昔单抗预处理可减轻小鼠肾脏IRI，其机制可能是抑制小鼠肾脏IRI早期浸润CD4^＋T淋巴细胞增殖后减少相关炎性因子聚集，从而减轻炎性损伤。Objective To investigate the effect and mechanism of basiliximab preconditioning on renal isehemia/repeffusion injury. Methods Fifty-four C57BL/6 mice were divided into three groups randomly： sham-operated group （Sham group） ; ischemia/repeffusion group （IR group） [ mice were injected with non-specific IgG （1 mg/kg） via tail vein 30 rain before the operation ] ; preconditioning with basifiximab group （Basiliximab group） [mice were injected with basiliximab （1 mg/kg） via tail vein 30 rain before the operation ]. Then we occluded the renal pedicles on both sides for 45 min. Serum creatinine （ Ser）, blood urea nitrogen （ BUN）, fractional excretion of sodium （FENa） , renal histology, CD4^＋ T lymphocytes, CD8^＋ T lymphocytes, intedeukin （IL） -2, tumor necrosis factor （TNF） -α, and IL-6 in blood or the kidney were examined after repeffusion for 1, 4, 24 h. Results Compared with the Sham group, the levels of Scr [ （ 174. 33 ±7. 69）, and （51.67 ±6. 56） μmol/L], BUN [ （69. 90 ± 1.68）, and （23.97 ± 2.12） μmol/L] , FENa, the pathological injury scores, IL-2, TNF-α, and IL-6 were increased significantly in IR group and Basiliximab group after repeffusion for 24 h. CD4^ ＋ T lymphocytes were also increased in Basifiximab and IR groups after repeffusion for 4 h. All these variables were significantly decreased in Basiliximab group as compared with IR group. Conclusion Preconditioning with basiliximab alleviated renal isehemia/repeffusion injury probably by inhibiting CD4^＋ T lymphocytes proliferation and decreasing the expression of pro-inflammatory cytokines.

关 键 词：巴利昔单抗 T淋巴细胞 肾缺血 再灌注损伤 

分 类 号：R692[医药卫生—泌尿科学]