壮骨止痛方对去势大鼠Wnt/β-catenin信号通路的影响
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摘要
目的:观察壮骨止痛方对去势大鼠骨组织Wnt/β-catenin信号通路的影响,探讨其治疗骨质疏松的机制。方法:60只3月龄SD雌性大鼠,按体重随机分为假手术组、空白组、模型组、壮骨止痛方组,15只/组。模型组、壮骨止痛方组采用双侧去卵巢建立绝经后骨质疏松大鼠模型,假手术组切除卵巢周围相应质量脂肪。术后5 d开始药物干预,连续13 w。取股骨,观察病理形态及Wnt7b、TCF3、GSK3β蛋白的表达。结果:与模型组相比,壮骨止痛方组骨小梁密度及梁髓比均提高。与模型组相比,壮骨止痛方组骨组织中Wnt7b、TCF3蛋白表达增高,GSK3β蛋白表达降低,差异具有统计学意义(P <0. 05)。结论:壮骨止痛方可通过上调去势大鼠骨组织中Wnt7b、TCF3蛋白表达,下调GSK3β蛋白表达来调控Wnt/β-catenin信号通路。
Objective: To explore the effect of Zhuanggu-Zhitong Prescription on Wnt/β-catenin Signaling Pathway of Ovariecto mized Rats with Osteoporosis,and to investigate its mechanism in anti-osteoporosis. Methods: 60 three-month old SD female rats,according to the weight,were randomly divided into sham-operated group,blank group,model group and Zhuanggu-Zhitong Prescription group,15 rats in each group. The model group's and Zhuanggu-Zhitong Prescription group' s rats were ovariectomized,and the sham-operated group's rats were excised equal weight fat. After 5 days of the operation,rats started to receive drug therapy. 13 weeks later, the bone tissue pathological change and the protein expression of Wnt7 b, TCF3, GSK3β were investigated. Results: Compared with the model group,Zhuanggu-Zhitong Prescription group increased the trabecular bone density and the ratio of bone trabecular to marrow cavity. Compared with the model group,the protein expression of Wnt7 b,TCF3 were increased in Zhuanggu-Zhitong Prescription group,and the protein expression of GSK3β was decreased,the difference had statistical significance( P ﹤ 0. 05). Conclusion: Zhuanggu-Zhitong Prescription can regulate the Wnt/β-catenin Signaling Pathway by rasing the expressions of protein Wnt7 b,TCF3 and reducing the expression of protein GSK3β.
Objective: To explore the effect of Zhuanggu-Zhitong Prescription on Wnt/β-catenin Signaling Pathway of Ovariecto mized Rats with Osteoporosis,and to investigate its mechanism in anti-osteoporosis. Methods: 60 three-month old SD female rats,according to the weight,were randomly divided into sham-operated group,blank group,model group and Zhuanggu-Zhitong Prescription group,15 rats in each group. The model group's and Zhuanggu-Zhitong Prescription group' s rats were ovariectomized,and the sham-operated group's rats were excised equal weight fat. After 5 days of the operation,rats started to receive drug therapy. 13 weeks later, the bone tissue pathological change and the protein expression of Wnt7 b, TCF3, GSK3β were investigated. Results: Compared with the model group,Zhuanggu-Zhitong Prescription group increased the trabecular bone density and the ratio of bone trabecular to marrow cavity. Compared with the model group,the protein expression of Wnt7 b,TCF3 were increased in Zhuanggu-Zhitong Prescription group,and the protein expression of GSK3β was decreased,the difference had statistical significance( P ﹤ 0. 05). Conclusion: Zhuanggu-Zhitong Prescription can regulate the Wnt/β-catenin Signaling Pathway by rasing the expressions of protein Wnt7 b,TCF3 and reducing the expression of protein GSK3β.
引文
[1]赵小辉,张金铭,张红艳,等.绝经后中老年女性骨质疏松发病相关因素分析[J].中国实验诊断学,2015,19(01):74-75.
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[8]梁文娜,李西海,李灿东.绝经后骨质疏松的核心病机—骨痿[J].中国老年学杂志,2015,35(18):5333-5335.
[9]徐峰,程坤,张春芳.绝经期妇女骨质疏松症的发病及中药治疗机理探究[J].中医药学报,2010,(01):46-48.
[10]朱莎莎.骨质疏松症的中医诊疗进展[J].实用中西医结合临床,2016,16(04):89-91.
[11]张雯,宇文亚,谢铭雁.原发性骨质疏松症中医循证临床实践指南应用释义[J].中华中医药杂志,2014,29(11):3479-3481.
[12] LERNER UH,OHLSSON C. The WNT system:background and its role in bone[J]. Journal of internalmedicine,2015,277(6):630-49.
[13] Ueno K,Hirata H,Hinoda Y,et al. Frizzled homolog proteins,microRNAs and Wnt signaling in cancer[J].International journal of cancer,2013,132(8):1731-40.
[14]周君,刘慧芳,何红晨,等.去卵巢对大鼠Wnt/β-catenin信号通路的影响.中国老年学杂志[J],2014,34(8):2152-2154.
[15]韦达隆,劳山,罗高斌. Wnt家族蛋白对骨细胞的作用研究进展[J].医学研究生学报,2016,29(05):551-555.
[16]吴也,廖洪利.基于Wnt/β-catenin信号通路的骨质疏松靶向治疗研究进展[J].化学与生物工程,2016,33(9):1-4.
[17]徐伟丽,牛玲玲,王文侠,等.经典Wnt信号通路对骨代谢的调节作用.中国骨质疏松杂志[J].2016,22(3):376-380.
[2]申浩,魏戌,谢雁鸣,等.绝经后骨质疏松症骨折危险因素及中医症状相关性研究[J].中国中西医结合杂志,2017,(01):50-56.
[3]蒋建发,孙爱君.中老年女性骨质疏松症流行病学现状、分类及诊断[J].中国实用妇科与产科杂志,2014,(05):323-326.
[4]李静,陈德才,王覃. 2016年《美国内分泌医师协会与美国内分泌协会绝经后骨质疏松症诊疗指南》解读[J].中国全科医学,2017,(08):891-895.
[5] THRASIVOULOU C,MILLAR M,AHMED A. Activation of intracellular calcium by multiple Wnt ligands and translocation ofβ-catenin into the nucleus:a convergent model of Wnt/Ca2+and Wnt/β-catenin pathways[J]. J Biol Chem,2013,288(50):35651-35659.
[6]祁珊珊,王永吉,辛薇. SD大鼠绝经后骨质疏松疾病动物模型的构建[J].临床与实验病理学杂志,2016,32(01):49-52.
[7]洪建勋,戴辉煌,李冠慧,等.绝经后骨代谢异常的中医病理特点探讨[J].世界中西医结合杂志,2016,(08):1166-1169.
[8]梁文娜,李西海,李灿东.绝经后骨质疏松的核心病机—骨痿[J].中国老年学杂志,2015,35(18):5333-5335.
[9]徐峰,程坤,张春芳.绝经期妇女骨质疏松症的发病及中药治疗机理探究[J].中医药学报,2010,(01):46-48.
[10]朱莎莎.骨质疏松症的中医诊疗进展[J].实用中西医结合临床,2016,16(04):89-91.
[11]张雯,宇文亚,谢铭雁.原发性骨质疏松症中医循证临床实践指南应用释义[J].中华中医药杂志,2014,29(11):3479-3481.
[12] LERNER UH,OHLSSON C. The WNT system:background and its role in bone[J]. Journal of internalmedicine,2015,277(6):630-49.
[13] Ueno K,Hirata H,Hinoda Y,et al. Frizzled homolog proteins,microRNAs and Wnt signaling in cancer[J].International journal of cancer,2013,132(8):1731-40.
[14]周君,刘慧芳,何红晨,等.去卵巢对大鼠Wnt/β-catenin信号通路的影响.中国老年学杂志[J],2014,34(8):2152-2154.
[15]韦达隆,劳山,罗高斌. Wnt家族蛋白对骨细胞的作用研究进展[J].医学研究生学报,2016,29(05):551-555.
[16]吴也,廖洪利.基于Wnt/β-catenin信号通路的骨质疏松靶向治疗研究进展[J].化学与生物工程,2016,33(9):1-4.
[17]徐伟丽,牛玲玲,王文侠,等.经典Wnt信号通路对骨代谢的调节作用.中国骨质疏松杂志[J].2016,22(3):376-380.