实用器官移植电子杂志

实用器官移植电子杂志 ›› 2020, Vol. 8 ›› Issue (5): 380-385.DOI: 10.3969/j.issn.2095-5332.2020.05.011

• 论著 • 上一篇    下一篇

卡培他滨对大鼠免疫功能影响的初步实验观察

张思睿 1 ，王政禄 2 ，刘涛 3 ，吴迪 4 ，侯文 3 ，郑虹 5
  

  1. 1. 天津医科大学一中心临床学院， 天津 300192 ； 2. 天津市第一中心医院病理科，天津 300192 ； 3. 天津市第一中心医院 国家卫生健康委员会危重病急救医学重点实验室，天津 300192 ； 4. 天津市第一中心医 院器官移植中心小儿肝移植科，天津 300192 ； 5. 天津市第一中心医院器官移植中心， 天津 300192
  • 出版日期:2020-09-20 发布日期:2021-06-02
  • 基金资助:

    中国医学科学院中央级公益性科研院所基本科研业务费专项资金（2018PT32021）；

    国家人类遗传资源 共享服务平台上海创新中心建设（YCZYPT[2017]02）

Experimental observation of capecitabine immunosuppressive effects in rats

Zhang Sirui 1 ，Wang Luzheng 2 ，Liu Tao 2 ，Wu Di 2 ，Hou Wen 2 ，Zheng Hong 5   

  1. 1. First Center Clinical Collage，Tianjin Medical University, Tianjin 300192, China ； 2. Department of Pathology, Tianjin First Central Hospital, Tianjin 300192, China ；  3. NHC Key Laboratory of Critical Care Medicine, Tianjin First Central Hospital, Tianjin 300192, China ； 4. Department of Pediatric Liver Transplantation, Organ Transplantation Center, Tianjin First Central Hospital, Tianjin 300192, China ； 5. Organ Transplantation Center, Tianjin First Central Hospital, Tianjin 300192.
  • Online:2020-09-20 Published:2021-06-02

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摘要：

目的 观察不同剂量卡培他滨（capecitabine，CAP）对大鼠免疫系统影响，探讨其对免疫 细胞的影响及作为免疫抑制剂的潜在可能性。方法 成年清洁级雄性 BN 大鼠 18 只，分为对照组（CON 组）、卡培他滨低剂量组（metronomic chemotherapy，MET 组）和高剂量组（most tolerance dose，MTD 组）， 分别经胃灌服生理盐水每次 1.2 ml、CAP 45 mg/kg 和 200 mg/kg，一日 2 次，连续喂服 21 d。给药前、给 药后第 7 天、14 天和 21 天测量大鼠体重并采集静脉血 3 ml，采用流式细胞和酶联免疫吸附试验（enzyme linked immunosorbent assay，ELISA）方法检测外周血总淋巴细胞数、T 淋巴细胞数、CD4+ 和 CD8+ T 淋巴细 胞数以及 IL-2 和 IFN-γ 含量。统计分析 3 组大鼠体重、总淋巴细胞数、T 淋巴细胞数、CD4+ 、CD8+ T 淋 巴细胞数和 IL-2、IFN-γ 变化趋势及相关性。结果 3 组大鼠于喂养 21 d 后均健康存活，体重逐渐增加， MET 组和 MTD 组体重增加程度低于 CON 组，其中 MTD 组和 CON 组于喂养 21 d 体重变化具有统计学意义 〔（214.17±20.6）g 比（235±5.48）g，P ＜ 0.05）〕。MET 组和 MTD 组总淋巴细胞数、T 淋巴细胞数、CD4+ 和 CD8+ T 淋巴细胞数均逐渐减少，给药第 21 天，MET 组、MTD 组与 CON 组淋巴细胞总数、T 淋巴细胞 数、CD4+ 和 CD8+ T 淋巴细胞数差异具有统计学意义（P ＜ 0.05），MTD 组与 MET 组间差异无统计学意义 （P ＞ 0.05）。MET 组和 MTD 组血清 IL-2 和 IFN-γ 含量逐渐下降，给药第 7 天、第 14 天及 21 天时 3 组间 差异有统计学意义（P ＜ 0.05）。MET 组和 MTD 组总淋巴细胞数、T 淋巴细胞数、CD4+ 和 CD8+ T 淋巴细胞 数减少与血清 IL-2 和 IFN-γ 下降呈正相关性（P ＜ 0.05）。结论 卡培他滨可降低大鼠外周血淋巴细胞数 并抑制 IL-2 和 IFN-γ 的分泌，对淋巴细胞的抑制强度与药物剂量呈正相关，可作为一种具有免疫抑制效 应的抗肿瘤药物，对肝癌肝移植患者治疗肿瘤复发具有应用价值。

关键词: 卡培他滨 , 大鼠 , 免疫抑制效应 , 淋巴细胞 , 实验观察

Abstract:

Objective To investigate the immunosuppressive effect of capecitabine（CAP）at different doses in rats and to explore its potential as an immunosuppressant. Methods Eighteen male BN rats were randomly divided into the control group（CON group），CAP low-dose group（metronomic chemotherapy，MET group），and CAP high-dose group（most tolerance dose，MTD group）. Three groups were administered with 1.2ml saline， 45 mg / kg and 200 mg / kg CAP by gastric gavage，respectively，the administration was performed twice per day and lasted for 21 days. The rat body weight was measured and 3 ml of venous blood was collected before administration and on the 7th，14th，and 21th day of administration. The total number of lymphocytes，T lymphocytes，CD4+ and CD8+ T lymphocytes in peripheral blood were measured by flow cytometry，and the concentrations of IL-2 and IFN-γ were measured by enzyme linked immunosorbent assay（ELISA）. Statistical analysis was performed on the changes of body weight，total lymphocyte count，T lymphocyte count，CD4+ and CD8+ T lymphocyte count，the level of IL-2 ，IFN-γ and their correlations in the three groups. Results All the rats in the three groups survived and gained weight gradually after 21 days of feeding. The weight gain of the MET group and MTD group was lower than that of the CON group，and the weight changes of the MTD group and the CON group were statistically significant at the 21th day 〔（214.17 ± 20.6）g vs.（235 ± 5.48）g，P ＜ 0.05〕. The total lymphocyte count，T lymphocyte count，CD4+ and CD8+ T lymphocyte count of MET group and MTD group decreased gradually. Compared with the CON group，the total lymphocyte count，T lymphocyte count，CD4+ and CD8+ T lymphocyte count of the MET group and the MTD group were significantly decreased on the 21th days after administration（P ＜ 0.05）. There was no significant difference between the MET groups and MTD groups（P ＞ 0.05）. Compared with the CON group，the levels of serum IL-2 and IFN-γ in the MET group and MTD group gradually decreased on the 7 th，14 th，and 21 th days after administration （P ＜ 0.05）. The decrease of the total lymphocyte count，T lymphocyte count，CD4 + and CD8+ T lymphocyte count in MET group and MTD group were positively correlated with the decrease of serum IL-2 and IFN-γ concentrations （P ＜ 0.05）. Conclusion Capecitabine can reduce the lymphocyte count in peripheral blood and inhibit the secretion of IL-2 and IFN-γ in rats，thus exhibiting immunosuppressive effect. The T cell suppressive intensity is positively correlated with the drug dose. Capecitabine has potential application value as an anti-rejection drug after liver transplantation.

Key words: Capecitabine, Rat, Immunosuppressive effect, Lymphocyte, Experimental observation

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