目的 探讨酒花提取物对去卵巢骨质疏松大鼠的作用及机制。方法 将 60 只雌性 SD 大鼠随机分为假 手术组、模型组、阳性对照组（戊酸雌二醇，0.105 mg·kg-1 ）和酒花提取物低、中、高剂量组（65.625、131.120、 196.875 mg·kg-1 ），每组 10 只。除假手术组外，其余各组大鼠均切除双侧卵巢，术后灌胃给药，每日 1 次，连 续给药 90 d。采用 HE 染色法观察大鼠骨组织病理形态变化，测定骨形态计量学参数，计算骨小梁数目 （Tb.N）、骨小梁厚度（Tb.Th）、骨小梁分离度（Tb.Sp）和骨小梁面积百分数（Tb.Ar）；测定大鼠骨组织生物力学指 标：最大载荷、弹性模量、断裂强度；采用 ELISA 法测定大鼠血清雌激素（E2 ）、抗酒石酸酸性磷酸酶 （TRACP5b）、骨钙素（OC）、骨特异性碱性磷酸酶（BALP）含量；采用全自动生化仪测定大鼠血清碱性磷酸酶 （ALP）含量；采用 RT-PCR 及 Western Blot 法检测大鼠胫骨组织 OPG、RANKL、ERα、ERβ、Wnt16、 β-catenin mRNA 及蛋白表达水平。结果 与假手术组相比，模型组大鼠胫骨骨小梁断裂，骨髓腔变大，呈现 骨质疏松结构；胫骨 Tb.N、Tb.Th、Tb.Ar 明显降低（P＜0.05），Tb.Sp 明显升高（P＜0.05）；股骨的最大载荷、 弹性模量和断裂强度均明显降低（P＜0.05）；血清 E2含量明显降低（P＜0.05），TRACP5b、OC、ALP、BALP 含 量均明显升高（P＜0.05）；胫骨组织的 OPG、OPG/RANKL、ERα、ERβ、β-catenin、Wnt16 mRNA 及蛋白表达 明显下调（P＜0.05），RANKL mRNA 及蛋白表达明显上调（P＜0.05）。与模型组相比，阳性对照组及酒花提取 物高剂量组的上述指标均明显回调（P＜0.05）。结论 酒花提取物对绝经后骨质疏松症具有一定的防治作用， 其作用机制可能与调控 Wnt/β-catenin 信号通路，进而调控 OPG/RANK/RANKL 信号通路有关。

Objective To investigate the effect and mechanism of Humulus lupulus Linn. extract on ovariectomized osteoporosis rats. Methods Sixty female SD rats were randomly divided into sham surgery group， model group， positive control group （estradiol valerate，0.105 mg·kg-1 ），low-，medium- and high- dose （65.625，131.120， 196.875 mg·kg-1 ） Humulus lupulus Linn. extract groups，with 10 rats in each group. Except for the sham surgery group， other groups had their ovaries removed. After surgery， rats were given drugs once daily by intragastric administration for 90 days. HE staining was used to observe the morphological changes of rat tibia. Bone morphometric parameters were measured，as well as trabecular number （Tb.N），trabecular thickness （Tb. Th）， trabecular separation （Tb. Sp）， and trabecular area （Tb. Ar） were calculated. Furthermore， we detected the biomechanical status of rat femur，such as maximum load，elastic modulus，and fracture strength. ELISA was used to detect the level of serum estrogen （E2 ），tartrate-resistant acid phosphatase （TRACP5b），osteocalcin （OC） and bone-specific alkaline phosphatase （BALP） in rats. Serum alkaline phosphatase （ALP） content was measured by using a fully automated biochemical analyzer. RT-PCR and Western Blot were used to detect mRNA and protein expression levels of OPG，RANKL，ERα，ERβ，Wnt16 and β-catenin in rat tibia. Results Compared with the sham surgery group，the tibial trabeculae of the model group was broken，the bone marrow cavity was enlarged， and osteoporotic structure was found. Tb.N，Tb.Th and Tb.Ar of tibia were significantly decreased （P＜0.05），and Tb.Sp was significantly increased （P＜0.05） . The maximum load，elastic modulus and fracture strength of femur were significantly decreased （P＜0.05） . Serum E2 content was significantly decreased （P＜0.05）， and serum TRACP5b， OC， ALP and BALP contents were significantly increased （P＜0.05） . The mRNA and protein expressions of OPG，OPG/RANKL，ERα，ERβ，β-catenin and Wnt16 were significantly decreased （P＜0.05）， while the mRNA and protein expressions of RANKL were significantly increased （P＜0.05） . Compared with model group，positive control group and high-dose Humulus lupulus Linn. extract group had improved the above indexes （P＜0.05） . Conclusion Humulus lupulus Linn. extract has a certain preventive and therapeutic effect on postmenopausal osteoporosis， and its mechanism may be related to the regulation of Wnt/β -catenin signaling pathway and the regulation of OPG/RANK/RANKL signaling pathway.

R285.5

国家科技重大专项（民口）课题（2020ZX09201-030）；新疆天然药物活性组分与释药技术重点实验室项目（XJDX1713）