异鼠李素抗骨质疏松作用及机制探讨

Antiosteoporotic effects and mechanisms of isorhamnetin against ovariectomy-induced osteoporosis in rats

目的:研究异鼠李素对去卵巢大鼠致骨质疏松骨的干预作用及机制。方法:取45只11周龄未经产SD雌性大鼠随机分为去卵巢假手术组(Sham)、去卵巢模型组(Model)和异鼠李素治疗组(IH)。用药12周后,micro-CT检测骨微结构形态并进行分析,ELISA法检测血清中抗酒石酸酸性磷酸酶(TRAP)和骨钙素(OC)水平,RT-PCR检测骨组织骨保护素(OPG)和NF-kB受体活化因子配体(RANKligands,RANKL)mRNA的表达,western blotting检测骨组织活化T细胞核因子c1(NFATc1)的表达。结果:与模型组比,异鼠李素可增加松质骨骨矿密度和体积,增加骨小梁厚度和数量,降低骨小梁间距(P<0.01);增加骨皮质(密质骨)骨矿密度和体积,使骨皮质增厚,骨皮质孔隙率减少。RT-PCR结果显示,异鼠李素显著增加去卵巢大鼠骨组织OPG mRNA的表达,降低RANKL mRNA的表达。ELISA检测显示,异鼠李素显著降低去卵巢大鼠血液TRAP和OC水平。western blotting检测结果显示,异鼠李素可显著降低骨组织NFATc1的表达。结论:异鼠李素具有防治去卵巢大鼠骨质疏松作用,其机制与调控骨组织RANKL/RANK/OPG信号通路有关。

OBJECTIVE To investigate effects of isorhamnetin against ovariectomy-induced osteoporosis as well as the underlying mechanisms. METHODS Forty-five virgin Sprague-Dawley rats of 1 l-week-old were randomly divided into 3 groups：sham control group （Sham）, ovariectomy model group （Model） and isorhamnetin treatment group （treated with Isorhamnetin at the dose of 30 mg·kg^-1·d^-1, IH）. After 12 weeks of treatment, bone microarchitecture was investigated with micro-CT and analyzed by CT Analyser, serum osteocalcin and tartrate-resistant acid phosphatase （TRAP） activities were detected with ELISA assay,expressions of bone osteoprotegerin （OPG） and RANKligands （RANKL） mRNA of NFKB were investigated by reverse transcriptase PCR （RT-PCR） and bone nuclear factor of activated T cells c1 （NFATcl） was detected by western blotting assay. RESULTS Compared with sham group, isorhamnetin strikingly increased bone mineral density （BMD） and bone volume of cancellous bone, improved microarchitecture of bone trabecula such as increasing bone trabecula quantity, thickness and decreasing trabecular width （P〈0. 01 ）, enhanced bone mineral density （BMD）, bone volume and thick- ness and decreased porosity of bone cortex （compact bone）. In addition, this treatment also increased expression of OPG mR- NA, reduced expression of RANKL mRNA in bone,inhibited increase of bone turnover markers such as serum OC and tartrate-resistant acid phos＇phatase （TRAP）, and decreased expression of NFATcl in bone. CONCLUSION Isorhamnetin has properties for resisting ovariectomy-induced osteoporosis,and the mechanism may be related to regulation of RANKL/RANK/OPG path-way in bone.