恒古骨伤愈合剂通过PI3K/AKT/GSK-3β信号通路治疗树鼩绝经后骨质疏松的作用机制
|
摘要
目的探讨恒古骨伤愈合剂(OK)通过磷脂酰肌醇-3激酶(PI3K)/蛋白激酶B(AKT)/糖原合成酶(GSK)-3β信号通路治疗绝经后骨质疏松(PMOP)的作用。方法 12月龄雌性实验树鼩60只,随机分成正常组、PMOP模型组、PMOP模型加低剂量OK组、PMOP模型加中剂量OK组、PMOP模型加高剂量OK组及PMOP模型加阳性药对照组,每组10只。通过摘除两侧卵巢制备PMOP树鼩模型,检测各组树鼩骨密度(BMD),收集血清和骨骼,检测血清雌二醇(E2)、骨碱性磷酸酶(BALP)、骨钙素(OC)和Ⅰ型原胶原N-端前肽(PINP)浓度;分别采用RT-qPCR和Western印迹法检测PI3K、AKT和GSK-3β的表达水平。结果 OK能提高模型组的BMD及其血清中E2、BALP、OC和PINP浓度,并且OK还能上调PI3K的表达水平和AKT的磷酸化水平,下调GSK-3β的表达水平,疗效均具有剂量依赖性。结论 OK可以通过促进骨细胞增殖的作用缓解PMOP,这种治疗作用可能是通过调控PI3K/AKT/GSK-3β信号通路实现的。
Objective To investigate the effects of osteoking (OK) on the postmenopausal osteoporosis via the PI3K/AKT/GSK-3β signal pathway.Methods 60 female experimental tree shrews were randomly divided into 6 groups.The BMD of all the shrewswere determined,the concentrations of E2,BALP,OC and PINP were detected. The expression levels of PI3K,AKT and GSK-3β weredetermined by RT-qPCR and Western blot respectively. Results OK enhanced the BMD,and increased the concentrations of serum E2,BALP,OC and PINP,moreover OK upregulated the expression level of PI3K and the phosphorylation level of AKT,downregulat-ed the expression level of GSK-3β,and all the therapeutic effects had a dose-dependent manner. Conclusions OK could alleviatePMOP by promoting the role of bone cell proliferation,which might be implicated in regulating PI3K/AKT/GSK-3β signaling pathway.
Objective To investigate the effects of osteoking (OK) on the postmenopausal osteoporosis via the PI3K/AKT/GSK-3β signal pathway.Methods 60 female experimental tree shrews were randomly divided into 6 groups.The BMD of all the shrewswere determined,the concentrations of E2,BALP,OC and PINP were detected. The expression levels of PI3K,AKT and GSK-3β weredetermined by RT-qPCR and Western blot respectively. Results OK enhanced the BMD,and increased the concentrations of serum E2,BALP,OC and PINP,moreover OK upregulated the expression level of PI3K and the phosphorylation level of AKT,downregulat-ed the expression level of GSK-3β,and all the therapeutic effects had a dose-dependent manner. Conclusions OK could alleviatePMOP by promoting the role of bone cell proliferation,which might be implicated in regulating PI3K/AKT/GSK-3β signaling pathway.
引文
1张立,葛焕琦,白立纬,等.杜仲叶醇防治糖尿病合并去势大鼠骨质疏松症的实验研究[J].中国老年学杂志,2003;23(6):370-2.
2 Liang W,Li X,Li Y,et al.Tongue coating microbiome regulates the changes in tongue texture and coating in patients with post-menopausal osteoporosis of Gan-shen deficiency syndrome type[J].Int J Mol Med,2013;32(5):1069-76.
3王艳杰,任艳玲,宋囡,等.左归丸对去卵巢大鼠股骨中Ⅰ型胶原mRNA表达的影响[J].中国老年学杂志,2012;32(23):5170-2.
4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):5333-5.
5王素彬,赵宏斌,胡敏,等.恒古骨伤愈合剂对骨质疏松性骨折兔骨密度及DKK-1蛋白的影响[J].中国中西医结合杂志,2015;35(8):1000-3.
6袁鑫,郑红,角建林,等.口服恒古骨伤愈药对骨质疏松性骨折树部分血液生化指标的影响[J].昆明医科大学学报,2017;38(7):12-5.
7支会英,李恩.补肾方药对去卵巢大鼠骨质疏松的骨组织ER表达的影响[J].中国中医基础医学杂志,2001;7(4):41-4.
8 Kawai M,M9dder UI,Khosla S,et al.Emerging therapeutic opportunities for skeletal restoration[J].Nat Rev Drug Discov,2011;10(2):141-56.
9王金凤,胡鹏,牛虹博,等.低温胁迫对鱼类PI3K/AKT/GSK-3β信号通路的影响[J].生物学杂志,2016;33(6):24-8.
10牛凯旋,刘思杨,冯猛,等.PI3K/Akt/GSK-3β/β-catenin信号通路促进神经细胞再生修复的研究进展[J].沈阳医学院学报,2017;19(1):69-71.
11许凯强,刘勇.AKT/GSK-3β-Wnt/β-catenin信号通路调控糖尿病血管钙化的研究新进展[J].中外医学研究,2017;15(10):162-4.
12 Mc Cubrey JA,Rakus D,Gizak A,et al.Effects of mutations in Wnt/beta-catenin,hedgehog,Notch and PI3K pathways on GSK-3 activity diverse effects on cell growth,metabolism and cancer[J].Biochim Biophys Acta,2016;1863(12):2942-76.
2 Liang W,Li X,Li Y,et al.Tongue coating microbiome regulates the changes in tongue texture and coating in patients with post-menopausal osteoporosis of Gan-shen deficiency syndrome type[J].Int J Mol Med,2013;32(5):1069-76.
3王艳杰,任艳玲,宋囡,等.左归丸对去卵巢大鼠股骨中Ⅰ型胶原mRNA表达的影响[J].中国老年学杂志,2012;32(23):5170-2.
4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):5333-5.
5王素彬,赵宏斌,胡敏,等.恒古骨伤愈合剂对骨质疏松性骨折兔骨密度及DKK-1蛋白的影响[J].中国中西医结合杂志,2015;35(8):1000-3.
6袁鑫,郑红,角建林,等.口服恒古骨伤愈药对骨质疏松性骨折树部分血液生化指标的影响[J].昆明医科大学学报,2017;38(7):12-5.
7支会英,李恩.补肾方药对去卵巢大鼠骨质疏松的骨组织ER表达的影响[J].中国中医基础医学杂志,2001;7(4):41-4.
8 Kawai M,M9dder UI,Khosla S,et al.Emerging therapeutic opportunities for skeletal restoration[J].Nat Rev Drug Discov,2011;10(2):141-56.
9王金凤,胡鹏,牛虹博,等.低温胁迫对鱼类PI3K/AKT/GSK-3β信号通路的影响[J].生物学杂志,2016;33(6):24-8.
10牛凯旋,刘思杨,冯猛,等.PI3K/Akt/GSK-3β/β-catenin信号通路促进神经细胞再生修复的研究进展[J].沈阳医学院学报,2017;19(1):69-71.
11许凯强,刘勇.AKT/GSK-3β-Wnt/β-catenin信号通路调控糖尿病血管钙化的研究新进展[J].中外医学研究,2017;15(10):162-4.
12 Mc Cubrey JA,Rakus D,Gizak A,et al.Effects of mutations in Wnt/beta-catenin,hedgehog,Notch and PI3K pathways on GSK-3 activity diverse effects on cell growth,metabolism and cancer[J].Biochim Biophys Acta,2016;1863(12):2942-76.