PTHrP1-34对荷瘤小鼠骨代谢与肿瘤生长情况的影响

目的研究甲状旁腺激素相关蛋白1-34（PTHrP1-34）对荷瘤小鼠骨代谢的影响,同时观察肿瘤生长情况。方法对照组、模型组、实验组4周龄健康雌性BALB/c小鼠各12只,模型组和实验组采用乳腺癌组织块悬浊液注射法制备小鼠乳腺癌模型,10d后模型组每日予以生理盐水腹腔注射,实验组每日予以PTHrP1-34400μg/（kg.bw）腹腔注射。用药35 d后测全身骨密度（BMD）、股骨灰干重比、骨代谢相关血清指标钙（Ca）、磷（P）、碱性磷酸酶（ALP）、骨钙素（OC）、Ⅰ型胶原C-末端交联顶端肽β（β-CTX）、骨唾液酸蛋白（BSP）],剥离肿瘤比较体积与质量。结果各组Ca水平差异无显著性（P〉0.05）。与对照组和模型组比较,实验组P、β-CTX、BSP等反映骨吸收的指标显著升高（P〈0.01或P〈0.05）,总ALP、BGP等反映骨形成的指标显著降低（P〈0.01或P〈0.05）;实验组BMD、股骨灰干重比均显著降低（P〈0.01）。与对照组相比,模型组各指标变化差异无显著性。实验组肿瘤体积和质量显著升高（P〈0.01）。结论在PTHrP1-34的作用下,荷瘤小鼠骨吸收大于骨形成,造成溶骨性骨破坏,骨密度降低,骨破坏释放的细胞因子可能促进肿瘤生长。

Destructive Effect of PTHrP1-34 on Bone Metabolism and Tumor Growth in Mice

Objective To observe the influence of PTHrP1-34 on the bone metabolism and tumor growth in mice. Methods Thirty six female healthy mice were included in this study. The mice were divided into control, model and experimental groups, 12 mice in each group. The mice in model and experimental groups were injected with suspension of human breast cancer MDA-MB-231 cells or inoculated with tumor tissue pieces. 10 days later, the mice of model group were injected with physiological saline intraperitoneally every day, and the mice of experimental group received PTHrP 400μg/kg once per day, for 35 consecutive days. The whole body bone mineral density （BMD）, ratio of ash weight to dry weight and bone metabolism-related parameters such as serum calcium （Ca）, phosphor （P）, alkaline phosphatase （ALP）, osteocalcin （OC）, Collagen type I cross-linked C-telopeptide β （β-CTX） ,bone sialoprotein （BSP） were assayed and the tumor sizes and weights were compared. Results Serum Ca level of different groups showed no statistically significant differences （ P 〉 0.05 ）. Compared with the other two groups, P,β-CTX and BSP levels of the experimental group were significantly increased （P 〈 0.01 or P 〈 0.05）, and the ALP and BGP levels were significantly reduced （ P 〈 0.01 or P 〈 0.05）. BMD and the ratio of ash weight to dry weight were significantly reduced （ P 〈 0.01 ）. There was no significant difference between the control group and model group （P 〉 0.05）. The tumor size and weight of experimental group were significantly higher than those of the model group. Conclusion Under the action of PTHrP1-34, bone resorption is greater than bone formation, leading to osteolytie destruction and reduced bone mineral density. In addition, some cytokines released during the bone destruction may promote the tumor growth.