淫羊藿总黄酮与己烯雌酚联用对去卵巢大鼠胫骨松质骨和皮质骨的影响

Effect of combination of Epimedium pubescens flavonoids and diethylstilbestrol on the proximal tibial metaphysis and tibial shaft in ovariectomized rats

目的:观察淫羊藿总黄酮(EF)与己烯雌酚(DES)联合用药对去卵巢大鼠胫骨松质骨和皮质骨的影响。方法:4月龄♀SD大鼠80只,随机分成8组,每组10只。除基础组和假手术组大鼠外,其余组行双侧卵巢切除术。基础组不给药,在实验开始时将其处死取材;假手术组和去卵巢组给予溶剂对照,其余分别为DES组(22.5μg.kg-1.d-1)、EF组(300mg.kg-1.d-1)、联合用药高剂量组(EF300mg.kg-1.d-1+DES22.5μg.kg-1.d-1)、联合用药中剂量组(EF150mg.kg-1.d-1+DES11.25μg.kg-1.d-1)、联合用药低剂量组(EF75mg.kg-1.d-1+DES5.625μg.kg-1.d-1)均灌胃给药,连续90d。大鼠处死后用骨组织形态计量学方法测量胫骨松质骨和皮质骨的动态和静态参数,同时测量血清雌二醇和子宫内膜厚度。结果:联合用药3个剂量组大鼠的胫骨上段骨小梁面积百分数、骨小梁数目均高于去卵巢组,而骨小梁分离度、单位骨小梁周长破骨细胞数、骨转换率均低于去卵巢组(P<0.05)。联合用药高剂量组的作用比单用DES强(P<0.05),而联合用药中、低剂量组的作用与DES相当(P>0.05)。与去卵巢组比较,联合用药3个剂量组大鼠胫骨中段皮质骨的动态和静态参数均无明显变化。联合用药3个剂量组大鼠子宫内膜厚度均小于DES组(P<0.05)。结论:淫羊藿总黄酮与己烯雌酚联合用药可有效预防去卵巢大鼠所致的胫骨松质骨丢失,其预防骨丢失作用比单用DES强,且对子宫刺激的作用比DES小。

OBJECtiVE To determine the effect of combination of Epimedium pubescens flavonoid （EF） and diethylstilbestrol（DES） on the proximal tibial metaphysis（PTM） and tibial shaft（Tx） in ovariectomized rats. METHODS Eighty 4-month-old virgin female Sprague-Dawley rats were randomly divided into 8 groups. Rats in basal group were sacrificed at age of 4. 5 months in the beginning of the study. Rats in sham group were sham-operated and treated by daily oral garage with vehicle. Rats in other six groups were bilaterally ovariectomized （OVX） and treated by either daily oral gavage with vehicle,or DES at 22.5μg·kg^-1·d^-1 ,or EF at 300 mg·kg^-1·d^-1 ,or combination of EF and DES at different doses （combination of EF 300 mg· kg^-1· d^-1 and DES22.5 μg·kg^-1·d^-1,of EF 150 mg· kg^-1· d^-1 and DES 11.25 μg· kg^-1, d^-1,of EF75 mg·kg^-1·d^-1 and DES 5. 625μg·kg^-1· d^-1） for 90 days. After 90 days of treatment,rats were sacrificed by cardiac puncture under sodium pentobarbital anesthesia. Bone histomorphometric analysis of the proximal tibial metaphysis （PTM） and tibial shaft （Tx） was performed in undecalcified sections. Serum estradiol（E2 ） and the uterine luminal epithelial thickness （ULET） was measured. RESULTS %Tb. Ar and Tb. N in all doses of combination of EF and DES groups was increased, while Tb. Sp,Oc. N and BFR/ BV was decreased,compared with OVX group. The bone-protective effect of high dose of combination of EF and DES was significantly greater than that of DES alone,while the effects of low and medium doses of combination of EF and DES were identical to that of DES. There was no significant change in bone histomorphometric parameters of Tx observed in all doses of combination of EF and DES, compared with OVX group. ULET in all doses of combination of EF and DES groups was lower than that in DES group. CONCLUSION Combination of EF and DES prevented OVX-indueed bone loss of PTM effectively. The protective effect of combination of EF and DES on bone loss in OVX rats was greater than that of DES alone, while the hypertrophic effect on uterine tissue of combination of EF and DES was lower than that of DES.