全氟辛烷磺酸对4T1荷瘤小鼠免疫状态的影响

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目的研究全氟辛烷磺酸(perfluorooctanesulfonate,PFOS)染毒对接种4T1乳腺癌细胞小鼠免疫状态的影响。方法将36只健康清洁级BALB/c雌性小鼠按体重随机分为3组,分别为对照(Tween-80)组及0.1、0.45 g/L PFOS染毒组,每组12只。采用自由饮水方式进行染毒,连续染毒56 d。染毒结束后,于小鼠右侧背部皮下注射2×10~5个4T1细胞,制作小鼠乳腺癌细胞荷瘤模型。通过real-time PCR方法检测小鼠Th1/Th2细胞因子IFN-γ和IL-4的mRNA表达水平;采用流式细胞术检测脾细胞中调节性T细胞(regulatory T cell,Treg)和髓样抑制性细胞(myeloid-derived suppressor cells,MDSC)的细胞分数。HE染色观察PFOS染毒对肿瘤组织的影响。结果与对照组相比,各浓度PFOS染毒组接种4T1乳腺癌细胞后小鼠脾细胞IFN-γmRNA表达水平升高,0.45 g/L染毒组小鼠脾细胞IL-4 mRNA表达水平升高,差异均有统计学意义(P<0.05)。与0.45 g/L PFOS染毒组相比,对照组和0.1 g/L PFOS染毒组小鼠接种4T1肿瘤细胞后脾细胞中MDSC的细胞分数均下降,差异均有统计学意义(P<0.05)。各组小鼠脾Treg细胞数量间比较,差异无统计学意义(P>0.05)。对照组和0.1、0.45 g/L PFOS染毒组荷瘤小鼠瘤块大小分别为(697.33±183.06)、(861.5±38.35)、(946.67±135.03)mm~3,各组间差异均无统计学意义(P>0.05);且肿瘤包块的大小随着PFOS染毒浓度的升高而呈增大趋势。0.45 g/L PFOS染毒组荷瘤小鼠肿瘤组织可见肿瘤细胞密集,核分裂较多,肿瘤血管更加丰富,与对照组比较,恶性程度更高。结论 PFOS染毒小鼠免疫状态向Th2型倾斜,接种4T1细胞后脾中MDSC的数量增多,肿瘤细胞恶性程度增加。 Objective To investigate the effect of perfluorooctanesulfonate (PFOS) on immune status in 4T1 breast cancer cells. Methods Thirty-six healthy BALB / c female mice were randomly divided into three groups according to body weight: control group (Tween-80) and 0.1,0.45 g / L PFOS exposure group (12 rats in each group). Adopt free drinking water to carry on the poisoning, continuous poisoning 56 d. After the exposure, 2 × 10 ~ 5 4T1 cells were subcutaneously injected into the right back of the mice to make the mouse breast cancer cell model. The mRNA expression levels of Th1 / Th2 cytokines IFN-γ and IL-4 in mice were detected by real-time PCR. The regulatory T cell (Treg) and myeloid inhibitory Cell fraction of myeloid-derived suppressor cells (MDSCs). The effect of PFOS on tumor tissue was observed by HE staining. Results Compared with the control group, the expression of IFN-γmRNA in the splenocytes of mice inoculated with 4T1 breast cancer cells at various concentrations of PFOS was increased, while the expression of IL-4 mRNA in spleen cells of mice treated with 0.45 g / L of LPS was increased , The differences were statistically significant (P <0.05). Compared with 0.45 g / L PFOS group, the cell fraction of MDSC in spleen cells of 4T1 tumor cells in control group and 0.1 g / L PFOS group were significantly decreased (P <0.05 ). There was no significant difference in the number of spleen Treg cells between the three groups (P> 0.05). The size of tumors in control group and 0.1,0.45 g / L PFOS group were (697.33 ± 183.06), (861.5 ± 38.35) and (946.67 ± 135.03) mm ~ 3, respectively, with no statistical difference among groups (P> 0.05). The size of tumor mass increased with the increase of PFOS concentration. Tumor cells in 0.45 g / L PFOS-treated tumor-bearing mice showed dense tumor cells, more nuclear fission, more tumor blood vessels, and higher malignancy compared with the control group. Conclusions The immune status of PFOS-exposed mice is inclined to Th2 type. The number of MDSCs in the spleen after 4T1 cells inoculation is increased, and the malignant degree of tumor cells is increased.
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