Article(id=1291404914794685015, tenantId=1146029695717560320, journalId=1246415772164075586, issueId=1291404807152067353, articleNumber=null, orderNo=null, doi=10.13699/j.cnki.1001-6821.2025.08.013, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1728230400000, receivedDateStr=2024-10-07, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1785824524829, onlineDateStr=2026-08-04, pubDate=1745769600000, pubDateStr=2025-04-28, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1785824524829, onlineIssueDateStr=2026-08-04, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1785824524829, creator=13701087609, updateTime=1785824524829, updator=13701087609, issue=Issue{id=1291404807152067353, tenantId=1146029695717560320, journalId=1246415772164075586, year='2025', volume='41', issue='8', pageStart='1051', pageEnd='1200', issueExtLink='null', onlineDate='null', pubDate='1745769600000', pubDateStr='2025-04-28', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1785824499166, creator='13701087609', updateTime=1785824499166, updator='13701087609', preIssue=null, nextIssue=null, articleTotal=null, ext=null, issueFiles=null, downloadFileDto=null}, startPage=1119, endPage=1125, ext={EN=ArticleExt(id=1291404915008594520, articleId=1291404914794685015, tenantId=1146029695717560320, journalId=1246415772164075586, language=EN, title=Research of Tonglagat-5 regulating PINK1/Parkin pathway-mediated autophagy on bone metabolism in osteoporotic mice, columnId=1246531407326105792, journalTitle=Chinese Journal of Clinical Pharmacology, columnName=Clinical and Basic Bridging Research, runingTitle=null, highlight=null, articleAbstract=
Objective To investigate the effects of Tonglagat-5, a Mongolian drug, on bone microstructure and bone metabolism in osteoporotic mice, and to explore the possible mechanisms of action based on phosphatase and tensin homologue-induced kinase 1 (PINK1)/Parkin-mediated mitophagy.
Methods Osteoporotic mouse model was established by ovariectomy (OVX). Osteoporotic model mice were randomly divided into model group (equal volume 0.9% NaCl by gavage), control group (estradiol valerate 1 mg·kg-1 by gavage), experimental group (0.05 g·kg-1 Tonglagat-5 solution by gavage) and combined group (0.05 g·kg-1 Tonglagat-5 solution by gavage + 50 mg·kg-1 Mdivi-1 by intraperitoneal injection), with 10 mice per group; ten mice were randomly selected as the sham-operation group. After 10 consecutive weeks of treatment, the bone mineral density (BMD) was measured by Micor-CT assay, the bone metabolism marker assay [C-terminal telopeptide of type Ⅰ collagen (CTx-Ⅰ), alkaline phosphatase (ALP) and bone Gla-protein (BGP)] were detected by kit, and the protein expression levels of translocase of outer mitochondrial membrane 20 (Tomm20), p62, PINK1 and Parkin were performed by Western blot.
Results The BMD in the sham-operation, model, control, experimental and combined groups were (0.23±0.02), (0.09±0.01), (0.22±0.03), (0.23±0.01) and (0.11±0.02) g·mm-3; the levels of CTx-Ⅰ were (14.58±1.22), (26.62±2.04), (16.44±2.31), (12.31±1.98) and (22.76±2.52) ng·mL-1; the levels of ALP were (4.87±1.12), (1.41±1.10), (3.03±1.07), (4.44±1.15) and (2.05±1.41) U·L-1; the levels of BGP were (9.35±1.06), (5.28±0.84), (7.76±0.35), (8.34±0.87) and (6.12±0.81) ng·mL-1; the relative expression levels of Tomm20 protein were 0.93±0.08, 0.10±0.01, 0.37±0.03, 0.84±0.06 and 0.28±0.03; the relative expression levels of p62 protein were 0.15±0.02, 0.93±0.09, 0.65±0.06, 0.37±0.04 and 0.86±0.06; the relative expression levels of PINK1 protein were 0.87±0.09, 0.14±0.02, 0.32±0.03, 0.69±0.06 and 0.26±0.03; the relative expression levels of Parkin protein were 0.79±0.08, 0.12±0.02, 0.26±0.04, 0.58±0.05 and 0.23±0.03, respectively. The above indexes in model group were compared those in sham-operation, control and experimental groups, the differences were statistically significant (all P<0.05).
Conclusion Tonglagat-5 is able to improve bone microstructure and bone metabolism and reduce bone loss in OVX mice, and the mechanism may be related to the activation of PINK1/Parkin pathway-mediated mitophagy to exert osteoprotective effects.
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目的 基于同源性磷酸酶张力蛋白诱导的激酶1（PINK1）/Parkin介导的线粒体自噬探讨蒙药通拉嘎-5对骨质疏松症（OP）小鼠骨微结构和骨代谢的影响，及其作用机制。
方法 通过卵巢切除（OVX）法构建OP小鼠模型。将OP模型小鼠随机分为模型组（灌胃等体积0.9% NaCl）、对照组（灌胃1 mg·kg-1戊酸雌二醇）、实验组（灌胃0.05 g·kg-1通拉嘎-5溶液）和联合组（灌胃0.05 g·kg-1通拉嘎-5溶液+腹腔注射50 mg·kg-1 Mdivi-1），每组10只；另取10只正常小鼠作为假手术组（灌胃等体积0.9% NaCl）。5组小鼠在连续给药10周后，用Micro-CT检测组织矿物质密度（BMD），用试剂盒检测骨代谢标志物[Ⅰ型胶原C末端肽（CTx-Ⅰ）、碱性磷酸酶（ALP）、骨钙素（BGP）]水平，用蛋白质印迹法检测线粒体外膜转运酶20（Tomm20）、p62、染色体10上删除的磷酸酶和Tensin同源物诱导激酶1（PINK1）和Parkin蛋白的表达水平。
结果 假手术组、模型组、对照组、实验组和联合组的BMD分别为（0.23±0.02）、（0.09±0.01）、（0.22±0.03）、（0.23±0.01）和（0.11±0.02）g·mm-3，CTx-Ⅰ水平分别为（14.58±1.22）、（26.62±2.04）、（16.44±2.31）、（12.31±1.98）和（22.76±2.52）ng·mL-1，ALP水平分别为（4.87±1.12）、（1.41±1.10）、（3.03±1.07）、（4.44±1.15）和（2.05±1.41）U·L-1，BGP水平分别为（9.35±1.06）、（5.28±0.84）、（7.76±0.35）、（8.34±0.87）和（6.12±0.81）ng·mL-1，Tomm20蛋白相对表达水平分别为0.93±0.08、0.10±0.01、0.37±0.03、0.84±0.06和0.28±0.03，p62蛋白相对表达水平分别为0.15±0.02、0.93±0.09、0.65±0.06、0.37±0.04和0.86±0.06，PINK1蛋白相对表达水平分别为0.87±0.09、0.14±0.02、0.32±0.03、0.69±0.06和0.26±0.03，Parkin蛋白相对表达水平分别为0.79±0.08、0.12±0.02、0.26±0.04、0.58±0.05和0.23±0.03。实验组、对照组和假手术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 通拉嘎-5能够改善OVX小鼠的骨微结构和骨代谢，减少骨质流失，其机制可能与激活PINK1/Parkin通路介导的线粒体自噬来发挥骨保护作用有关。
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包乌云毕力格（1980-），男，主治医师，主要从事骨科相关的研究工作
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