膝关节机械加载改善小鼠乳腺癌肺转移的实验研究

Experimental study on knee loading to improves pulmonary metastasis of breast cancer in mice

目的:探讨脉冲式机械加载对小鼠乳腺癌肺转移的抑制作用。方法:30只4~6周龄BALB/c雌性小鼠随机分为模型组与治疗组,通过每只尾静脉注射鼠源性乳腺癌细胞(4T1),建立小鼠乳腺癌肺转移模型。治疗组小鼠每天接受膝关节机械加载治疗,治疗18 d后处死。取肺脏,解剖显微镜下计数肺部转移瘤数目,TUNEL法分析肿瘤细胞凋亡情况,墨汁灌注肺脏切片观察转移灶周围血管生成情况,免疫组化分析细胞增殖和血管生成情况。结果:与模型组相比,治疗组肺部转移瘤数目明显减少(P<0.05),TUNEL阳性细胞明显增多(P<0.01),转移灶周围血管面积明显降低(P<0.05)。结论:机械加载能够有效地抑制小鼠乳腺癌肺转移,该抑制作用可能与机械加载能够促进肿瘤细胞凋亡和抑制肿瘤血管生成有关。

Objective： To investigate whether knee loading can inhibit pulmonary metastasis of breast cancer in mouse model. Methods： Thirty BALB/c female mice were randomly divided into model group and treated group. Mice were conducted tail vein injection of 5 ×10^4 murine breast cancer cells to establish the small breast cancer pulmonary metastasis model. Knee loading was applied per day for 18 days. After the mice were sacrificed, lungs were taken and observed under a dissecting microscope. The number of pulmonary metastasis was counted, and TUNEL staining was used to analyze the apoptosis of tumor cell. Furthermore, ink perfusion was conducted to observe angiogenesis on pulmonary metastase. Immunohistochemical analysis was performed to observe proliferation and angiogenesis of tumor. Results： Compared with the model group, the number of pulmonary metastases was significantly reduced （P〈0.05） in the treated group, and TUNEL-positive cells was significantly increased （P〈0.01）. Furthermore, compared with the model group, the treated mice showed a lower vascular area around lung tumor （P〈0.05）. Conclusion： Knee loading can effectively suppress pulmonary metastasis of breast cancer in mice model, and the loading effect may be associated with promotion of tumor cell apoptosis and inhibition of angiogenesis.