Mechanism of lactate in mediating bone anabolism induced by high-intensity interval training

ZHANG Wen-hua; XU Zhi-tao; GUAN Xuan; CAO Yun-qiu

doi:10.11659/jjssx.10E025037

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Mechanism of lactate in mediating bone anabolism induced by high-intensity interval training

Basic Research | 更新时间：2026-06-16

- Mechanism of lactate in mediating bone anabolism induced by high-intensity interval training
- JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY Vol. 35, Issue 6, Pages: 505-512(2026)
- 作者机构：
  
  1.昆山市中西医结合医院康复医学科，江苏昆山 215332
  2.浙江省人民医院康复医学科，浙江杭州 310015
- 作者简介：
- 基金信息：
- DOI：10.11659/jjssx.10E025037
  CLC： R322.8
- Received：14 October 2025，
  
  Published：25 June 2026
- 稿件说明：
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张文华,徐智韬,管璇等.乳酸介导高强度间歇训练骨合成代谢的作用机制[J].局解手术学杂志,2026,35(06):505-512.

ZHANG Wen-hua,XU Zhi-tao,GUAN Xuan,et al.Mechanism of lactate in mediating bone anabolism induced by high-intensity interval training[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2026,35(06):505-512.
张文华,徐智韬,管璇等.乳酸介导高强度间歇训练骨合成代谢的作用机制[J].局解手术学杂志,2026,35(06):505-512. DOI： 10.11659/jjssx.10E025037.

ZHANG Wen-hua,XU Zhi-tao,GUAN Xuan,et al.Mechanism of lactate in mediating bone anabolism induced by high-intensity interval training[J].JOURNAL OF REGIONAL ANATOMY AND OPERATIVE SURGERY,2026,35(06):505-512. DOI： 10.11659/jjssx.10E025037.

摘要

目的

探究乳酸（Lact）在高强度间歇训练（HIIT）介导的骨合成代谢中的作用及机制。

方法

①将18只小鼠分为Con组（不进行任何处理）、HT组（仅进行HIIT）、Lact组（仅注射L-乳酸钠），每组6只，然后取血进行Lact检测。②通过卵巢切除术（OVX）建立绝经后骨质疏松小鼠模型，然后分为OVX组（仅建模）、OVX+HIIT组（建模后进行HIIT）、OVX+HIIT+乳酸转运体抑制剂α-氰基-4-羟基肉桂酸（α-CHCA）组（建模后，进行HIIT的同时腹腔注射α-CHCA）及OVX+Lact组（建模后皮下注射L-乳酸钠），每组10只；Sham组小鼠不建模（

=10）。采用Micro-CT扫描分析骨微结构参数，通过HE染色和抗酒石酸酸性磷酸酶（TRAP）染色分别计数成骨细胞数量（N.Ob）和破骨细胞数量（N.Oc/BS）；使用Scanco Micro-CT40扫描仪扫描分析以下微结构参数：骨密度（BMD）、骨体积分数（BV/TV）、骨小梁数量（Tb.N）、骨小梁厚度（Tb.Th）、骨小梁分离度（Tb.Sp）、皮质骨厚度（Ct.Th）及骨面积分数（BA/TA）。③体外培养小鼠成骨前体细胞MC3T3-E1，并分为Control组（正常培养）、Lact-C组（给予20 mmol/L的L-乳酸钠）、α-CHCA组（给予0.4 mmol/L α-CHCA）及Lact+α-CHCA组（同时加入20 mmol/L L-乳酸钠和0.4 mmol/L α-CHCA）。碱性磷酸酶（ALP）染色、茜素红染色观察成骨分化和矿化结节；免疫荧光染色检测微管相关蛋白1轻链3（LC3）表达；Western blot检测Runt相关转录因子2（Runx2）、Osterix（Osx）和骨桥蛋白（OPN）、自噬相关蛋白Beclin-1、自噬接头蛋白p62、GATA结合蛋白4（GATA4）、Parkin蛋白表达及LC3-Ⅱ/LC3-Ⅰ水平。

结果

①小鼠进行HIIT 30 min后血浆Lact水平达峰值，Lact注射60 min后血浆Lact水平达峰值。②与OVX组相比，OVX+HIIT组和OVX+Lact组骨组织中的BMD、BV/TV、Tb.N、Tb.Th、Ct.Th、BA/TA和N.Ob均增加，Tb.Sp、N.Oc/BS减少，差异均有统计学意义（

0.05）。③体外实验显示：Lact处理增加成骨细胞矿化和分化活性，显著增强自噬流，表现为LC3-Ⅱ/LC3-Ⅰ、Beclin-1及成骨分化标志物Runx2、Osx和OPN表达升高，同时p62及GATA4蛋白表达下降，而抑制Lact转运均削弱此效应。

结论

在HIIT介导的骨合成代谢中，Lact通过激活自噬相关蛋白促进GATA4蛋白表达下降，进而驱动成骨细胞分化，缓解骨质疏松。

Abstract

Objective

To investigate the role and mechanism of lactate （Lact） in bone anabolism mediated by high-intensity interval training （HIIT）.

Methods

①Eighteen mice were divided into Con group （no treatment）， HT group （underwent HIIT only）， and Lact group （injected with sodium L-lactate only）， with 6 mice in each group. Blood samples were then obtained for Lact detection. ②Postmenopausal osteoporosis mouse model was established by ovariectomy （OVX）. The mice were then divided into OVX group （OVX only）， OVX+HIIT group （underwent HIIT after modeling）， OVX+HIIT+lactate transporter inhibitor α-cyano-4-hydroxycinnamic acid （α-CHCA） group （underwent HIIT combined with intraperitoneal injection of α-CHCA after modeling）， and OVX+Lact group （underwent subcutaneous injection of sodium L-lactate after modeling）， with 10 mice in each group. Mice in the Sham group （

=10） did not undergo modeling. Bone microstructural parameters were analyzed using Micro-CT scanning. The number of osteoblasts （N.Ob） and number of osteoclasts （N.Oc/BS） were assessed by HE staining and tartrate‑resistant acid phosphatase （TRAP） staining， respectively. The following microstructural parameters were measured using a Scanco Micro-CT40 scanner： bone mineral density （BMD）， bone volume over total volume （BV/TV）， trabecular number （Tb.N）， trabecular thickness （Tb.Th）， trabecular separation （Tb.Sp）， cortical thickness （Ct.Th）， and bone area over total area （BA/TA）. ③Mouse preosteoblast MC3T3-E1 cells were cultured in vitro and divided into the Control group （normal culture）， Lact-C group （treated with 20 mmol/L sodium L-lactate）， α‑CHCA group （treated with 0.4 mmol/L α-CHCA）， and Lact+α-CHCA group （treated with both 20 mmol/L sodium L-lactate and 0.4 mmol/L α-CHCA）. Osteogenic differentiation and mineralized nodule formation were evaluated by alkaline phosphatase （ALP）

staining and alizarin red S staining.LC3 expression was detected by immunofluorescence staining. Western blot was used to detect the expression of Runt‑related transcription factor 2 （Runx2）， Osterix （Osx）， osteopontin （OPN）， autophagy‑related protein Beclin‑1， autophagy adaptor protein p62， GATA‑binding protein 4 （GATA4）， Parkin protein， and the LC3‑Ⅱ/LC3‑Ⅰ ratio.

Results

①In mice， plasma Lact levels peaked at 30 minutes after HIIT and at 60 minutes after Lact injection. ②Compared with the OVX group， the OVX+HIIT and OVX+Lact groups exhibited increased BMD， BV/TV， Tb.N， Tb.Th， Ct.Th， BA/TA and N.Ob in bone tissue， as well as decreased Tb.Sp and N.Oc/BS， all with statistically significant differences （

0.05）. ③In vitro experiments showed that Lact treatment enhanced osteoblast mineralization and differentiation activity， significantly promoted autophagic flux， as evidenced by increased LC3-Ⅱ/LC3-Ⅰ ratio， Beclin-1 level and osteogenic markers Runx2， Osx， and OPN expression， decreased p62 and GATA4 proteins. These effects were attenuated by inhibiting Lact transport.

Conclusion

In HIIT-mediated bone anabolism， Lact promotes the decrease of GATA4 protein expression by activating autophagy-related proteins， thereby driving osteoblast differentiation and alleviating osteoporosis.

关键词

Keywords

references

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