USDA, Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand Forks, North Dakota 58202-9034, USA.
Ann N Y Acad Sci. 2011 Dec;1240:E31-5. doi: 10.1111/j.1749-6632.2011.06370.x.
Proinflammatory cytokines are primary mediators of bone loss in estrogen deficiency. This study determined whether alpha-1 antitrypsin (AAT), a multifunctional protein with proteinase inhibitor and anti-inflammatory activities, mitigates bone loss induced by estrogen deficiency. Mice were either sham-operated or ovariectomized and injected with either AAT or phosphate buffered saline (PBS). Ovariectomy resulted in decreased wet uterus weight, significant bone loss, increased serum leptin concentrations, and higher body weight compared to sham. AAT injection increased tibial trabecular bone volume/total volume and trabecular thickness compared to PBS injection in ovariectomized mice. Ovariectomized mice with AAT treatment had higher uterus weight, lower serum osteocalcin levels, fewer bone marrow tartrate-resistant acid phosphatase-positive osteoclasts, and less expression of calcitonin receptor in bone than that in PBS-injected mice. These data demonstrate that AAT mitigates ovariectomy-induced bone loss in mice possibly through inhibiting osteoclast activity and bone resorption.
促炎细胞因子是雌激素缺乏导致骨丢失的主要介质。本研究旨在确定α-1 抗胰蛋白酶（AAT），一种具有蛋白酶抑制剂和抗炎活性的多功能蛋白，是否能减轻雌激素缺乏引起的骨丢失。小鼠行假手术或卵巢切除术，并注射 AAT 或磷酸盐缓冲盐水（PBS）。与假手术组相比，卵巢切除术导致湿子宫重量降低、骨丢失显著、血清瘦素浓度升高和体重增加。与 PBS 注射组相比，AAT 注射增加了卵巢切除小鼠胫骨小梁骨体积/总体积和小梁厚度。AAT 治疗的卵巢切除小鼠的子宫重量更高，血清骨钙素水平更低，骨髓抗酒石酸酸性磷酸酶阳性破骨细胞更少，骨中降钙素受体的表达也低于 PBS 注射组小鼠。这些数据表明，AAT 可能通过抑制破骨细胞活性和骨吸收来减轻卵巢切除小鼠的骨丢失。
