Article(id=1291404720879432403, tenantId=1146029695717560320, journalId=1246415772164075586, issueId=1291404681641713991, articleNumber=null, orderNo=null, doi=10.13699/j.cnki.1001-6821.2025.07.017, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1730476800000, receivedDateStr=2024-11-02, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1785824478597, onlineDateStr=2026-08-04, pubDate=1744819200000, pubDateStr=2025-04-17, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1785824478597, onlineIssueDateStr=2026-08-04, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1785824478597, creator=13701087609, updateTime=1785824478597, updator=13701087609, issue=Issue{id=1291404681641713991, tenantId=1146029695717560320, journalId=1246415772164075586, year='2025', volume='41', issue='7', pageStart='901', pageEnd='1050', issueExtLink='null', onlineDate='null', pubDate='1744819200000', pubDateStr='2025-04-17', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1785824469242, creator='13701087609', updateTime=1785824469242, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext=null, issueFiles=null, downloadFileDto=null}, startPage=989, endPage=994, ext={EN=ArticleExt(id=1291404721336611540, articleId=1291404720879432403, tenantId=1146029695717560320, journalId=1246415772164075586, language=EN, title=Effects of zoledronic acid regulating MEK/ERK pathway on bone metabolism in hypoxic osteoporosis rats, columnId=1246531407326105792, journalTitle=Chinese Journal of Clinical Pharmacology, columnName=Clinical and Basic Bridging Research, runingTitle=null, highlight=null, articleAbstract=
Objective To explore the effects and mechanism of zoledronic acid on bone metabolism in osteoporosis rats under hypoxic environment.
Methods The rat model of osteoporosis in hypoxia environment was established by bilateral ovary extraction combined with low-pressure oxygen chamber feeding, and was randomly divided into model group, control group and experimental -L, -M, -H groups, with 10 rats per group; another 10 normal rats were selected as the normal group. Experimental -L, -M, -H groups were given 2.5, 5.0 and 10.0 mg·kg-1 zoledronic acid by subcutaneous injection, once a week. Control group was given 0.105 mg·kg-1 estradiol valerate by intragastric administration, once a day. Normal and model groups were injected with equivalent 0.9% NaCl by subcutaneous injection. Six groups were treated for 4 weeks. The serum levels of tartrate-resistant acid phosphatase (TRAP), alkaline phosphatase (ALP) and bone gla protein (BGP) were detected by enzyme-related immunosorbent assay. The bone mineral density (BMD) was measured by dual-energy X-ray. The expression levels of mitogen extracellular signal-regulated kinase (MEK)/extracellular regulated protein kinases (ERK) in femur were detected by Western blot.
Results The TRAP levels of experimental-M, experimental -H, control, model and normal groups were (78.06±1.16), (69.39±1.44), (70.19±1.24), (94.39±1.04) and (64.95±1.19) U·L-1; the ALP levels were (61.72±3.10), (45.40±0.82), (43.53±1.52), (88.69±2.29) and (42.01±1.56) U·L-1; the BGP levels were (14.82±0.28), (12.29±0.28), (12.92±0.29), (19.96±0.46) and (11.79±0.59) ng·mL-1; the BMD levels were (0.28±0.02), (0.35±0.04), (0.38±0.03), (0.16±0.02) and (0.41±0.06) g·cm-2; the relative expression levels of p-MEK protein were 0.64±0.06, 0.84±0.05, 0.78±0.01, 0.15±0.06 and 0.88±0.04; the relative expression levels of p-ERK protein were 0.70±0.03, 0.95±0.02, 0.84±0.07, 0.29±0.03 and 0.97±0.06, respectively. Compared with the model group, the above indexes in the experimental-M, -H groups and control group were statistically significant (all P<0.05).
Conclusion Zoledronic acid can improve bone mineral density and bone metabolism in hypoxic osteoporosis rats, the mechanism may be related to the regulation of MEK/ERK pathway.
, authors=Hai-qi XU, Li-xin YANG, Jin-juan LI, Juan ZHANG, Qian-jun ZHU, Qin-fang ZHU, Na MI, Ye WANG, authorsList=Hai-qi XU, Li-xin YANG, Jin-juan LI, Juan ZHANG, Qian-jun ZHU, Qin-fang ZHU, Na MI, Ye WANG, authorCompany=null, correspAuthors=Li-xin YANG, authorNote=null, correspAuthorsNote=null, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, fund=null), CN=ArticleExt(id=1291404721730876117, articleId=1291404720879432403, tenantId=1146029695717560320, journalId=1246415772164075586, language=CN, title=唑来膦酸调节MEK/ERK通路对低氧环境下骨质疏松大鼠骨代谢的影响, columnId=1246531407485489349, journalTitle=中国临床药理学杂志, columnName=临床与基础桥接研究, runingTitle=null, highlight=null, articleAbstract=
目的 探索唑来膦酸对低氧环境下骨质疏松大鼠骨代谢的影响，及其作用机制。
方法 用双侧卵巢摘除法联合低压氧舱饲养构建低氧环境骨质疏松大鼠模型，并随机分为模型组、对照组和低、中、高剂量实验组，每组10只；另取10只正常大鼠作为正常组。低、中、高剂量实验组分别皮下注射2.5、5.0、10.0 mg·kg-1唑来膦酸，每周1次；对照组灌胃给予0.105 mg·kg-1戊酸雌二醇，每天1次；正常组和模型组均皮下注射等量0.9% NaCl。6组大鼠均连续给药4周。用酶联免疫吸附试验法检测血清抗酒石酸酸性磷酸酶（TRAP）、碱性磷酸酶（ALP）和骨钙素（BGP）水平，用双能X线小动物骨密度测定仪测定大鼠骨密度（BMD），用蛋白质印迹法检测股骨中丝裂原活化蛋白激酶（MEK）/细胞外调节蛋白激酶（ERK）的表达水平。
结果 中、高剂量实验组和对照组、模型组、正常组的TRAP水平分别为（78.06±1.16）、（69.39±1.44）、（70.19±1.24）、（94.39±1.04）和（64.95±1.19）U·L-1，ALP水平分别为（61.72±3.10）、（45.40±0.82）、（43.53±1.52）、（88.69±2.29）和（42.01±1.56）U·L-1，BGP水平分别为（14.82±0.28）、（12.29±0.28）、（12.92±0.29）、（19.96±0.46）和（11.79±0.59）ng·mL-1，BMD分别为（0.28±0.02）、（0.35±0.04）、（0.38±0.03）、（0.16±0.02）和（0.41±0.06）g·cm-2，磷酸化MEK蛋白相对表达水平分别为0.64±0.06、0.84±0.05、0.78±0.01、0.15±0.06和0.88±0.04，磷酸化ERK蛋白相对表达水平分别为0.70±0.03、0.95±0.02、0.84±0.07、0.29±0.03和0.97±0.06。中、高剂量实验组和对照组的上述指标与模型组比较，在统计学上差异均有统计学意义（均P<0.05）。
结论 唑来膦酸能够提高低氧环境下骨质疏松大鼠的骨密度，改善骨代谢水平，其机制可能与调节MEK/ERK通路有关。
, authors=许海琦, 杨历新, 李金娟, 张娟, 朱千君, 朱沁芳, 米娜, 王叶, authorsList=许海琦, 杨历新, 李金娟, 张娟, 朱千君, 朱沁芳, 米娜, 王叶, authorCompany=null, correspAuthors=杨历新, authorNote=
许海琦（1987-），女，副主任医师，主要从事内分泌代谢病学相关的临床诊疗工作与研究
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