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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。
Objective To investigate the effect of sirolimus combined with Huaier particles and thymosin α-1 triple anti-tumor therapy on T lymphocyte in rat liver transplantation model of liver transplantation. Methods Seventy-two Sprague-Dawley (SD) rats were randomly divided into triple group, sirolimus group, Huaier group, thymosin group, positive control group and blank group, with 12 rats in each group. In addition to the blank group, the remaining groups were used to establish the animal model of liver cancer recurrence after liver transplantation. After the model was established, positive control group rats were identified model was successfully established. Flow cytometry was used to detect the percentage of CD4 + T lymphocytes (Tregs), CD4 + T lymphocytes (CD4 + T%) and CD8 + T lymphocytes to the total number of lymphocytes (CD8 + T%). Spearman rank correlation was used to analyze the relationship between Treg% and CD4 + T%, CD8 + T% and CD4 + / CD8 + T lymphocyte ratio (CD4 + / CD8 +). Results Histopathological examination of rat liver tissue suggested successful modeling. Treg% of the positive control group was higher than that of the blank group, the difference was statistically significant (P <0.05). Treg% in triad group was significantly lower than that in positive control group, thymosin group and Huaier group, which was significantly higher than that in blank group (all P <0.05). Compared with the positive control group, the CD4 + T% and CD8 + T% of the triple group, the sirolimus group and the thymosin group were significantly higher (all P <0.05). The triple combination group had higher CD4 + T% and CD8 + T% than thymosin group, sirolimus group and Huaier group (all P <0.05). Treg% in peripheral blood of each group was negatively correlated with CD4 + T%, CD8 + T% and CD4 + / CD8 +, and triple anti-tumor therapy could reduce the negative correlation between Treg% and CD4 + / CD8 +. Conclusion The triple anti-tumor therapy based on sirolimus can reduce the level of Treg in peripheral blood of rats and increase the number of T lymphocytes and the ratio of CD4 + / CD8 +, which play an important role in anti-tumor cell growth and proliferation.