仙茅、淫羊藿及其配伍从神经-内分泌途径调控糖皮质激素性骨质疏松症的作用  

Synergistic effect of Curculigo orchioides,Epimedium brevicornu and their pair on regulating glucocortiside-induced osteoporosis from neuroendocrine pathway

作　　者：张泉龙 何心芸溪 俞阳 刘燕 张巧艳 秦路平 ZHANG Quan-long;HE Xin-yun-xi;YU Yang;LIU Yan;ZHANG Qiao-yan;QIN Lu-ping(School of Pharmacy,Zhejiang Chinese Medical University,Hangzhou 311402,China)

机构地区：[1]浙江中医药大学药学院,杭州311402

出　　处：《中华中医药杂志》2022年第5期2563-2568,共6页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(No.81973534);浙江省基础公益研究计划(No.LY19H280002)。

摘　　要：目的:从神经内分泌调控途径探究仙茅、淫羊藿及配伍对大鼠地塞米松致骨质疏松(GI OP)的协同保护作用。方法:建立小鼠地塞米松致GIOP模型,随机将小鼠分为模型组(DEX组)、仙茅水提物组(CUR组)、淫羊藿水提物组(EPI组)和联合用药组(CUR+EPI组),另设空白对照组(NOR组),每组8只,连续给药8周后,micro-CT测定骨密度(BMD)和骨形态计量学参数,ELISA试剂盒检测血清骨代谢生化指标和内分泌相关指标,Western blot和免疫组化法检测下丘脑FoxO1和c-Jun蛋白表达。结果:与DEX组比较,CUR+EPI组大鼠BMD,骨表面积/骨体积(BS/TV),相对骨体积(BV/TV),连接骨密度(Conn.D)值均显著增加(P<0.05,P<0.01),骨小梁分离度(Tb.Sp)值显著降低(P<0.01)。同时,CUR组、EPI组和CUR+EPI组大鼠血清骨转换指标PINP和CTX-1显著降低(P<0.01),OPG、OPG/RANKL显著增加(P<0.05,P<0.01),血清GH、IGF-1和LH水平显著升高(P<0.05,P<0.01),生长抑素(SS)和去甲肾上腺素(NE)水平显著降低(P<0.05,P<0.01)。金氏公式分析仙茅与淫羊藿联合用药在上述指标上均表现出协同增效作用。Western blot及免疫组化结果显示,DEX组能够抑制大鼠下丘脑弓状核FoxO1活性并提高c-Jun活性,CUR组和CUR+EPI组FoxO1表达显著升高(P<0.01),EPI组和CUR+EPI组p-c-Jun表达显著降低(P<0.05,P<0.01)。结论:仙茅、淫羊藿及其配伍通过改善骨组织计量学,修复股骨显微变化,有效抑制GIOP大鼠骨丢失,同时能促进GHRH/GH/IGF-1轴和抑制交感神经兴奋,间接调控骨代谢,其机制与调节下丘脑FoxO1和c-Jun信号通路有关,药对协同作用效果更优。Objective:To investigate the synergistic protective effect of Curculigo orchioides(CUR),Epimedium brevicornu(EPI)and their compatibility(CUR+EPI)on dexamethasone induced osteoporosis rats(GIOP)through regulating neuroendocrine pathway.Methods:The GIOP model was established by injecting dexamethasone into the muscles of male rats,and randomly divided into the DEX group,CUR group,EPI group and CUR+EPI group,a normal control group(NOR group)was set up,8 in each group.The rats were oral administrated once a day for 8 weeks.Bone mineral density(BMD)and bone morphonetric parameters were detected by micro-CT.The levels of bone metabolism index and neuroendocrine index in serum were determined by ELISA method.The expression of FoxO1 and c-Jun in hypothalamus were determined by Western blot and immunohistochemical method.Results:Compared with DEX group,the BMD,BS/TV,BV/TV and Conn.D values in CUR+EPI group were significantly increased(P<0.05,P<0.01),while the Tb.N value,PINP and CTX-1 was significantly decreased(P<0.01).Meanwhile,the OPG and OPG/RANKL GH,IGF-1,and LH levels in CUR,EPI or CUR+EPI groups were significantly increased while the SS and NE levels were significantly decreased(P<0.05,P<0.01).EPI+CUR herb pair treatment had synergistic improvement effects on those factors by the Gold’s formula analysis.Furthermore,DEX group inhibited FoxO1 activity and improved c-Jun activity in the hypothalamic arcuate nucleus.While CUR group and CUR+EPI group increased FoxO1 expression(P<0.01),and EPI group and CUR+EPI group decreased p-c-Jun expression(P<0.05,P<0.01).Conclusion:CUR,EPI and their herb pair can inhibit bone loss in GIOP rats effectively through improving the bone tissue metrology,repairing the microscopic changes of femur bones.The mechanism was related to that they can promote GHRH/GH/IGF-1 axis and inhibit sympathetic excitation,through regulate FoxO1 and c-Jun signal pathways in the hypothalamus.

关 键 词：仙茅 淫羊藿 糖皮质激素性骨质疏松 下丘脑 FOXO1 c-Jun 

分 类 号：R285.5[医药卫生—中药学]