以西罗莫司为基础三联抗肿瘤疗法对大鼠肝癌肝移植复发模型T淋巴细胞的影响

Influence of sirolimus based triple anti-tumor therapy on T lymphocyte of rat model with liver cancer recurrence after transplantation

    摘要
  • 摘要:
      目的  探讨以西罗莫司为基础联合槐耳颗粒、胸腺肽α-1的三联抗肿瘤疗法对大鼠肝癌肝移植复发模型T淋巴细胞的影响。
      方法   72只Sprague-Dawley(SD)大鼠以随机数字法分为三联组、西罗莫司组、槐耳组、胸腺肽组、阳性对照组、空白组, 每组12只。除空白组外, 其余各组均采用化学诱癌法建立模拟肝癌肝移植术后复发的动物模型。模型建立后, 取阳性对照组大鼠鉴定模型是否成功建立。采用流式细胞术分别检测各组大鼠外周血调节性T细胞(Treg)占CD4+T淋巴细胞比例(Treg%)、CD4+T淋巴细胞占淋巴细胞总数比例(CD4+T%)及CD8+T淋巴细胞占淋巴细胞总数比例(CD8+T%)。采用Spearman秩相关分析Treg%与CD4+T%、CD8+T%及CD4+/CD8+T淋巴细胞比值(CD4+/CD8+)之间的关系。
      结果   大鼠肝癌组织病理切片提示建模成功。阳性对照组的Treg%高于空白组, 差异有统计意义(P<0.05)。三联组的Treg%明显低于阳性对照组、胸腺肽组和槐耳组, 明显高于空白组(均为P<0.05)。与阳性对照组比较, 三联组、西罗莫司组和胸腺肽组的CD4+T%和CD8+T%较高, 差异有统计学意义(均为P<0.05)。三联组的CD4+T%和CD8+T%均高于胸腺肽组、西罗莫司组和槐耳组, 差异有统计学意义(均为P<0.05)。各组大鼠的外周血Treg%与CD4+ T%、CD8+ T%和CD4+/CD8+均呈负相关, 且三联抗肿瘤疗法可降低Treg%与CD4+/CD8+之间的负性相关关系。
      结论   西罗莫司为基础的三联抗肿瘤疗法可降低大鼠外周血Treg水平, 提高T淋巴细胞数量及CD4+/CD8+, 发挥抗肿瘤细胞生长和增殖的作用。

     

    Abstract:
      Objective   To explore the influence of triple anti-tumor therapy which bases on sirolimus combined huaier granule and thymosin α-1 on T lymphocyte of rat model with liver cancer recurrence after transplantation.
      Methods   Seventy-two Sprague-Dawley(SD)rats were randomly divided into triple therapy group, sirolimus group, huaier-granule group, thymosin α-1 group, positive-control group and blank group(n=12 in each group). Except the blank group, rats in all the other groups were established the simulation animal model of liver cancer recurrence after liver transplantation by chemical-induced method. After the model was established, rats in the positive control group were executed to appraise whether the model was successful. The proportion of regulatory T cells (Treg) of CD4+ T lymphocytes in peripheral blood (Treg%), the percentage of CD4+ T lymphocyte of total lymphocyte(CD4+T%)and the percentage of CD8+ T lymphocyte of total lymphocyte (CD8+T%), were detected by the flow cytometry respectively. The relationship between Treg% and CD4+ T%, CD8+ T%, the ratio of CD4+/CD8+ T lymphocytes(CD4+/CD8+)was analyzed by the method of Spearman rank correlation.
      Results   Pathological section of rat liver tissue suggested that the rat model was established successfully. Treg% of positive control group was higher than that of blank group, the difference had statistical significance(P<0.05). Treg% of triple therapy group was significantly lower than that of the positive control group, huaier-granule group, thymosin α-1 group, and significantly higher than the blank group(all in P<0.05). Compared with positive-control group, CD4+T% and CD8+T% of triple therapy group, sirolimus group and thymosin α-1 group were significantly higher (all in P<0.05). CD4+T% and CD8+T% of triple therapy group were significantly higher than those of thymosin α-1 group, sirolimus group and huaier-granule group (all in P<0.05). The relationship between Treg% and CD4+T%, CD8+T%, CD4+/CD8+ in peripheral blood were negatively correlated for rats in each group. In addition, the triple anti-tumor therapy decreased the negative correlation between Treg% and CD4+/CD8+.
      Conclusions   Sirolimus based triple anti-tumor therapy can decrease the peripheral blood Treg level of the liver cancer rat, increase the number of T lymphocyte and CD4+/CD8+, and play the role of anti tumor cell growth and proliferation.

     

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