积雪草酸对大鼠绝经后骨质疏松症的治疗作用及机制研究  

Therapeutic effect and mechanism of asiatic acid on postmenopausal osteoporosis in rats

作　　者：张亮亮 赵程锦[1] 周煜虎[1] 曹博[1] 段明明[1] 冯阳阳[1] ZHANG Liangliang;ZHAO Chengjin;ZHOU Yuhu;CAO Bo;DUAN Mingming;FENG Yangyang(Department of Traumatic Orthopedics,Affiliated Hospital of Yan’an University,Yan’an 716000,China)

机构地区：[1]延安大学附属医院创伤骨科,陕西延安716000

出　　处：《陕西医学杂志》2023年第12期1624-1630,共7页Shaanxi Medical Journal

基　　金：国家自然科学基金资助项目(82160431)。

摘　　要：目的:探讨积雪草酸对大鼠绝经后骨质疏松症(OP)的治疗作用及相关机制。方法:采用一次性手术摘除双侧卵巢方式构建绝经后OP大鼠模型,分为模型组(9只)、雌二醇组(10只)、积雪草酸低剂量组(10只)、积雪草酸中剂量组(10只)和积雪草酸高剂量组(10只)。另取9只大鼠作为假手术组。观察骨组织病理改变、骨密度及微结构,以及血清骨代谢指标、骨代谢相关基因及蛋白表达。结果:雌二醇组和积雪草酸低、中、高剂量组均可减轻骨组织病理改变,增加骨密度,改善骨微结构。与假手术组比较,模型组大鼠股骨骨密度(BMD)、骨体积分数(BV/TV)、骨小梁数目(Tb.N)、骨小梁厚度(Tb.Th)下降,结构模式指数(SMI)和骨小梁分离度(Tb.Sp)上升,血清骨碱性磷酸酶(BALP)水平下降,Ⅰ型胶原交联氨基端肽(NTX-Ⅰ)和抗酒石酸酸性磷酸酶(TRAP)水平上升,骨组织音猬因子(SHH)、细胞表面跨膜蛋白Patched1(Ptc1)、7次跨膜蛋白(Smo)、Gli家族锌指蛋白-1(Gli1)、矮小相关转录因子2(Runx2)、骨保护素(OPG)、成骨细胞特异性转录因子(Osx)mRNA和蛋白表达下降,细胞核因子-κB受体活化因子(RANKL)mRNA和蛋白表达上升(均P<0.05)。与模型组比较,雌二醇组和积雪草酸低、中、高剂量组大鼠股骨BMD、BV/TV、Tb.N、Tb.Th上升,SMI和Tb.Sp下降,血清BALP水平上升,NTX-Ⅰ和TRAP水平下降,骨组织SHH、Ptc1、Smo、Gli1、Runx2、OPG、Osx mRNA和蛋白表达上升,RANKL mRNA和蛋白表达下降(均P<0.05)。雌二醇组和积雪草酸低剂量组上述指标比较差异无统计学意义(均P>0.05)。积雪草酸低、中、高剂量组上述指标呈剂量依赖性(均P<0.05)。结论:积雪草酸可治疗绝经后OP,可能与激活Hedgehog信号通路相关。Objective:To investigate the therapeutic effect of asiatic acid on postmenopausal osteoporosis(OP)rats and its related mechanism.Methods:Postmenopausal OP rats model was constructed by using disposable surgical excision bilateral ovaries,and divided into model group(9 rats),estradiol group(10 rats),asiatic acid low-dose group(10 rats),asiatic acid medium-dose group(10 rats)asiatic acid high-dose group(10 rats),another 9 rats were enrolled sham-operation group.The pathological changes,bone density and microstructure of bone tissue,serum bone metabolism indexes,and the expression of bone metabolism-related genes and proteins were observed.Results:The estradiol group and the asiatic acid low-,medium-,and high-dose groups could reduce the pathological changes of bone tissue,increase bone mineral density,and improve bone microstructure.Compared with the sham-operation group,in the model group,the femoral BMD,BV/TV,Tb.N,Tb.Th decreased,SMI and Tb.Sp increased,and serum BALP level decreased,NTX-Ⅰand TRAP increased,and the mRNA and protein expressions of SHH,Ptc1,Smo,Gli1,Runx2,OPG,Osx in bone tissue decreased,RANKL mRNA and protein expression increased(all P<0.05).Compared with the model group,in the estradiol group and the asiatic acid low-,medium-,and high-dose groups,BMD,BV/TV,Tb.N,Tb.Th increased,SMI and Tb.Sp decreased,serum BALP level increased,and NTX-Ⅰand TRAP levels decreased,and the mRNA and protein expressions of SHH,Ptc1,Smo,Gli1,Runx2,OPG,and Osx in bone tissue increased,while RANKL mRNA and protein expression decreased(all P<0.05).There was no significant difference in the above indicators between the estradiol group and the asiatic acid low-dose group(all P>0.05).The above indicators in the asiatic acid low-,medium-and high-dose groups showed a dose-dependent manner(all P<0.05).Conclusion:Asiatic acid can treat osteoporosis,which may be related to activating Hedgehog signaling pathway.

关 键 词：骨质疏松症 积雪草酸 HEDGEHOG信号通路 骨代谢 微结构 大鼠 

分 类 号：R580[医药卫生—内分泌]