葛根对睾丸切除骨质疏松模型小鼠骨密度和骨构造的作用

Effects of puerariae radix on bone density and bone microarchitecture in castrated mice with osteoporosis

背景:研究证实,葛根不仅能够预防卵巢切除雌激素不足骨质疏松模型小鼠骨密度及骨量的下降,而且能够改善骨微细构造,可用于女性闭经后骨质疏松症的预防与治疗。其对男性骨质疏松的治疗是否具有相似的疗效?目的:课题以更接近应用为目的,观察未经提取的植物药葛根对雄激素不足骨质疏松模型小鼠骨密度和骨构造的影响。方法:8周龄雄性ddY小鼠48只,体质量32～35g,随机数字表法分为假手术组,模型组,低、中、高剂量葛根组和雌二醇组,每组8只。假手术组暴露睾丸与附睾,切除周围脂肪组织;其余各组小鼠摘除双侧睾丸。术后假手术组、模型组和雌二醇组都给予普通饲料,低、中、高剂量葛根组给予含有5%,10%和20%葛根粉的饲料。雌二醇组17β-雌二醇通过体内小渗透泵自动给药0.03μg/d。饲料给予均为4.0g/d。4周后,检测精囊质量,以双能X射线骨密度测定仪检测股骨骨密度,显微CT分析股骨远端干骺端海绵骨微细构造。结果与结论:模型组股骨全体骨密度下降了10.9%,这种下降被低剂量葛根完全抑制,被中剂量葛根抑制进一步加强,但两者差异无显著性意义;高剂量葛根组骨密度较模型组、假手术组分别高出26.1%,12.4%,作用强度与雌二醇相当。低剂量葛根完全抑制了雄激素缺乏导致的股骨骨小梁数目下降以及骨小梁间距增大,中剂量葛根抑制作用更强,但两组之间差异无显著性意义;高剂量葛根组抑制作用最强,能够增加骨量和骨小梁数目达到显著高于假手术组水平。葛根各剂量对精巢无刺激作用。提示葛根在不刺激精囊的条件下,低、中剂量葛根可完全抑制雄激素缺乏所致的骨密度和骨量下降,改善骨构造,高剂量效果更显著,与雌二醇作用相当。

BACKGROUND： Studies confirmed that pueraria can not only prevent the reduced bone mineral density and bone mass in the ovariectomy-caused estrogen deficiency mice with osteoporosis model, also improve bone micro-structure, it can be used for osteoporosis prevention and treatment in women after menopause. Does it exhibit a similar effect fpr the treatment of male osteoporosis？ OBJECTIVE： To investigate the influence of puerariae Radix （PR） crude drug on the bone mineral density （BMD） and bone micro-architecture in androgen-deficiency mice with osteoporosis model. METHODS： A total of 48 ddY male mice, aged 8 weeks and weighing 32-35 g, were randomly divided into 6 groups： sham group, orchidectomized group, PR with low, middle and high dose group, 17β-estradiol group. Each group contained 8 mice. In sham group, mice were sham operated to expose testis and epididymis, removing surrounding fat tissue; in other groups, mice were orchidectomized. After operation, sham group and model group were fed normal diet, while PR with low, middle and high dose groups were fed a diet containing 5%, 10% and 20% PR, and 17β-estradiol group was fed a normal diet with subcutaneous administration of 17β-estradiol 0.03 μg/d. The diet dosage was all 4.0 g/d. Four weeks after experiment, the mice were anesthetized and killed, and the weight of the seminal vesicle was measured. Dual-energy X-ray was used to detect BMD in femurs, and micro-CT analysis for distal femur metaphysis sponge bone microstructure. RESULTS AND CONCLUSION： The whole femoral BMD was significantly decreased by 10.9% in the model group, and the decrease in BMD was completely prevented by intake of the diet with the low dose of PR. Intake of the diet with the middle dose of PR further increased BMD in the model group, but no significant differences were observed. Furthermore, the high dose of PR administration significantly increased BMD by 26.1% and 12.4% respectively compared with model group and sham operated group, and the potency was similar to that of 17β-estradiol. Intake of the diet with the low dose of PR completely prevented the decrease in trabecular bone volume and trabecular number, and restored the increase in trabecular separation in mice caused by androgen deficiency. Intake of the diet with the middle dose of PR could enhance the inhibition effect, but there was no significant difference; intake of the diet with the high dose of PR exhibited the strongest effect on the inhibition, it further significantly increased trabecular bone volume and trabecular number compared with sham operated group. The seminal vesicle was not affected by the administration of any doses of PR. Without influence on the seminal vesicle, the low and middle dose of PR can completely inhibit the decreasing BMD and bone mass caused by androgen deficiency in mice, as well as improve bone structure, high dose of PR exhibits a significant effect and similar to 17β-estradiol.