中国临床药理学杂志2025，Vol.41Issue(8)：1119-1125,7.DOI:10.13699/j.cnki.1001-6821.2025.08.013
通拉嘎-5调控PINK1/Parkin通路介导自噬对骨质疏松小鼠骨代谢的研究
Research of Tonglagat-5 regulating PINK1/Parkin pathway-mediated autophagy on bone metabolism in osteoporotic mice
摘要
Abstract
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-1Mdivi-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 typeⅠ 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.关键词
通拉嘎-5/骨质疏松症/线粒体自噬/骨代谢Key words
Tonglagat-5/osteoporosis/mitophagy/bone metabolism分类
中医学引用本文复制引用
包乌云毕力格,图布新..通拉嘎-5调控PINK1/Parkin通路介导自噬对骨质疏松小鼠骨代谢的研究[J].中国临床药理学杂志,2025,41(8):1119-1125,7.基金项目
内蒙古自治区自然科学基金资助项目(2020MS08101) （2020MS08101）
中西医结合骨病临床医学研究中心开放课题资助项目(2024FYKF041) （2024FYKF041）
