激素联合去卵巢诱导大鼠股骨骨质疏松复合模型的建立

Establishment of a rat osteoporotic model by ovariectomy combined with glucocorticoid exposure

背景:使用激素的绝经后女性人群在临床上并不少见,由于具备雌激素水平不足及使用激素两个因素,故骨量流失的速度更快,更容易发生脆性骨折。目前对于研究与该人群相匹配的复合模型,即激素联合去卵巢诱导的骨质疏松模型的水平不够深入,相关的分子机制尚未完全阐明。目的:构建激素联合去卵巢股骨骨质疏松大鼠模型,并探讨复合模型的分子机制。方法:将3月龄雌性SD大鼠随机分为空白对照组、假手术组及模型组,各10只。空白对照组不造模,假手术组切开腹部剪取少量脂肪组织,模型组从腹部切除双侧卵巢同时连续4周注射地塞米松。结果与结论:造模后4周,与空白对照组及假手术组相比,模型组离体股骨骨密度、骨小梁数量、相对骨体积显著降低,骨小梁间距显著提高,且骨小梁间距增宽和结构破坏,骨皮质变薄,骨皮质厚度降低,骨组织Runx2 m RNA表达显著下调,Ⅰ型胶原α1、过氧化物酶体增殖物激活受体γmR NA表达明显升高,组织蛋白酶k mR NA表达呈上升趋势,但差异无显著性意义。提示激素联合去卵巢可快速诱导大鼠股骨骨质疏松,其机制可能与下调Runx2,上调Ⅰ型胶原α1、过氧化物酶体增殖物激活受体γ的mR NA表达有关。

BACKGROUND： There are many postmenopausal women taking hormone, which leads to much loss of bone mass, further inducing fragility fractures. The studies on the hormone exposure combined with ovariectomy-induced osteoporotic model are still immature, and the related molecular mechanism remains unclear. OBJECTIVE： To establish the rat osteoporotic model induced by ovariectomy combined with glucocorticoid exposure and to explore the underlying molecular mechanism. METHODS： Thirty 3-month-old female Sprague-Dawley rats were randomly divided into blank control, sham and model groups （/7=10 per group）. The rats in the blank control group received no intervention; rats in the sham group were clipped off a little of coeliac adipose tissue; the model rats received bilateral ovariectomy and 4-week administration of glucocorticoid. RESULTS AND CONCLUSION： At 4 weeks after modeling, compared with blank control and sham groups, the model group showed significantly lower bone mineral density of the femur, number of bone trabeculae and bone volume/total volume, and significantly wider bone trabecular spacing. Additionally, the model group revealed the damaged bone trabecular structure and thiner cortical bone. The expression level of Runx2 was downregulated whereas both collagen type 1 al and peroxisome proliferators activated receptor y mRNA were upregulated in the model group. These findings suggest that ovariectomized rats exposed to glucocorticoid rapidly develop femur osteoporosis, maybe by downregulating the expression of Runx2, as well as upregualting collagen type 1 01 and peroxisome proliferators activated receptor y mRNA.