加味身痛逐瘀汤调控Wnt/β-catenin信号通路对大鼠骨质疏松症的防治作用

Therapeutic effect of Jiawei Shentong Zhuyu decoction on osteoporosis related to regulating Wnt/β-catenin signaling pathway in rats

目的:探讨加味身痛逐瘀汤防治去卵巢大鼠骨质疏松症(OP)的疗效及其可能作用机制。方法:将60只SD大鼠,体重(245±25)g,随机分为假手术组、模型组、戊酸雌二醇组、加味身痛逐瘀汤高、中、低剂量组,每组10只。利用双侧卵巢切除法制备大鼠骨质疏松模型,手术模型制备成功后,戊酸雌二醇组大鼠给予戊酸雌二醇(剂量为0.09μg/g)灌胃;加味身痛逐瘀汤治疗组大鼠给予加味身痛逐瘀汤(剂量为32、16、8 g/kg)灌胃;假手术组和模型对照组大鼠给予等体积蒸馏水灌胃,连续灌胃给药2个月。利用双能X线骨密度检测仪、HE染色法及Western blot分别测定骨密度,观察骨组织病理形态变化,分析大鼠股骨组织中Wnt、Wnt1、β-catenin、cyclin D1蛋白表达情况。结果:与假手术组比较,模型对照组骨密度明显降低(P<0.05),骨微结构遭到严重破坏,股骨组织中Wnt、Wnt1、β-catenin、cyclin D1蛋白的表达量显著降低(P<0.05)。与模型对照组相比,戊酸雌二醇组、加味身痛逐瘀汤高、中、低剂量组骨密度显著升高(P<0.05),骨微结构明显改善,股骨组织中Wnt、Wnt1、β-catenin、cyclin D1蛋白的表达量显著升高(P<0.05),且加味身痛逐瘀汤高剂量组和戊酸雌二醇组对骨密度及蛋白表达量的影响最为显著。结论:加味身痛逐瘀汤可能通过调节Wnt/β-catenin信号通路提高骨质疏松症大鼠的骨密度以及改善骨组织形态,从而发挥抗骨质疏松的作用。

Objective:To investigate the effect and possible mechanism of Jiawei Shentong Zhuyu decoction on osteoporosis(OP)in ovariectomy rats.Methods:60 SD rats,weighing(245±25)g,were randomly divided into sham operation group,model group,estradiol valerate group,and the high,medium and low dose groups of Jiawei Shentong Zhuyu decoction,with 10 rats in each group.The rat osteoporosis model was prepared by bilateral ovariectomy.After the successful preparation of the surgical model,the rats in the estradiol valerate group were given estradiol valerate(0.09μg/g)by gavage.The rats in the treatment group were given Jiawei Shentong Zhuyu decoction(32,16,8 g/kg)by gavage.Rats in sham operation group and model control group were gavaged with distilled water of equal volume for 2 months.Dual-energy X-ray bone mineral density detector,HE staining method and Western blot were used to determine the bone mineral density,observe the pathological morphological changes of bone tissue,and analyze the expression of Wnt,Wnt1,β-catenin and cyclin D1 proteins in rat femoral tissue.Results:Compared with sham operation group,the bone density of the model control group was significantly decreased(P<0.05),the bone microstructure was seriously damaged and the expression of Wnt,Wnt1,β-catenin,cyclin D1 protein in femoral tissue was significantly decreased(P<0.05).Compared with the model control group,the bone density increased significantly(P<0.05),the bone microstructure was obviously improved,and the expression of Wnt,Wnt1,β-catenin and cyclin D1 in the femoral tissue was significantly increased(P<0.05)in the estradiol valerate group and Jiawei Shentong Zhuyu decoction high,middle and low dose groups,and the effects of Jiawei Shentong Zhuyu decoction high-dose group and estradiol valerate on bone density and protein expression were the most significant.Conclusion:Jiawei Shentong Zhuyu decoction may play an anti-osteoporosis effect by regulating Wnt/β-catenin signaling pathway to improve bone density and improve bone morphology in osteoporosis rats.