针刺通过调节DKK1通路调控骨代谢改善去卵巢模型大鼠骨质疏松的机制研究

Acupuncture regulates bone metabolism by regulating DKK1 pathway to improve osteoporosis in OVX rats

目的探讨针刺通过调节DKK1通路调控骨代谢对于去卵巢模型大鼠(ovariectomized rats,OVX)骨质疏松的影响及其机制。方法采用经典的双侧卵巢切除进行雌性SD大鼠的原发性骨质疏松造模,阿伦磷酸盐阳性药物对照组服用阿伦磷酸盐治疗,各期针灸组采取针刺双侧“肾腧”穴。观察针刺治疗对OVX大鼠全身骨量、生物力学功能、腰椎椎体的病理形态学以及Wnt3a、β-catenin、Dkk1含量的影响。结果与假手术模型组相比,OVX模型组、药物干预组、各期针刺治疗组大鼠的腰椎骨密度均出现显著下降(P<0.01)。药物干预组、各期针刺治疗组腰椎骨密度均高于OVX模型组(P<0.05)。与假手术模型组相比,OVX模型组、药物干预组、各期针刺治疗组大鼠的胫骨最大载荷力、弹性模量均出现显著下降(P<0.01)。药物干预组、各期针刺治疗组的胫骨最大载荷力均高于OVX模型组(P<0.01)。相较于OVX模型组,药物干预组、各期针刺治疗组的细胞肿胀和胞浆空泡样改变明显减轻,骨小梁结构的破坏情况有明显改善。与模型组比较,药物干预组、各期针刺治疗组大鼠腰椎体中DKK1表达下降、β-catenin、Wnt3a表达增加(P<0.01)。结论针刺刺激“肾腧”穴后,通过调节细胞因子DKK1、β-catenin、Wnt3a可起到调节骨代谢的作用,从而有效地干预骨质疏松造成的骨质下降。

Objective To investigate the effect of acupuncture on bone metabolism regulation in ovariectomized rats. Methods Female SD rats were treated with classical bilateral oophorectomy primary osteoporosis rat model,the positive control group was treated with alendronate sodium,and the acupuncture groups were treated with acupuncture points of bilateral " Shenshu". To observe the effect of acupuncture treatment on bone mass,biomechanical function,pathomorphology of lumbar vertebrae and contents of Wnt3a,β-catenin and Dkk1 in ovariectomized rats. Results Compared with the sham operation model group,the lumbar vertebral bone density in the ovariectomized model group,the drug intervention group,and the acupuncture treatment group decreased significantly( P < 0. 01).Lumbar vertebral bone density in drug intervention group and acupuncture treatment group at each stage was higher than that in OVX model group( P < 0. 05). Compared with the sham operation model group,the maximal tibial load and elastic modulus of the ovariectomized model group,the drug intervention group,and the acupuncture treatment group were significantly decreased( P<0.01).The maximal tibial load force of the drug intervention group and the acupuncture treatment group at each stage was higher than that of the OVX model group( P<0.01).Compared with the ovariectomized model group,the cell swelling and cytoplasmic vacuolar changes in the drug intervention group and the acupuncture treatment group at each stage were significantly reduced,and the destruction of bone trabecular structure was significantly improved. Compared with the model group,the expression of DKK1 in drug intervention group and the acupuncture treatment group at each stage decreased,and the expression of β-catenin and Wnt3a increased( P<0.01). Conclusion The acupuncture stimulation of " Shenshu " can regulate cytokines DKK1,β-catenin and Wnt3a,thus to modulate bone metabolism so as to effectively interfere the osteopathy caused by osteoporosis.