Therapeutic effect and underlying mechanism of low-intensity focused ultrasound on knee arthrofibrosis in rats

TANG Qiuyu; MAO Lin; BAI Dingqun; YI Weiwei

doi:10.16016/j.2097-0927.202501064

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Therapeutic effect and underlying mechanism of low-intensity focused ultrasound on knee arthrofibrosis in rats

Basic Medicine | 更新时间：2025-06-11

- Therapeutic effect and underlying mechanism of low-intensity focused ultrasound on knee arthrofibrosis in rats
- Journal of Army Medical University Vol. 47, Issue 11, Pages: 1208-1216(2025)
- 作者机构：
  
  重庆医科大学附属第一医院康复医学科，重庆市卫生健康委物理医学与精准康复重点实验室，重庆
- 作者简介：
- 基金信息：
  
  the National Natural Science Foundation for Young Scholars of China(82402966);the Key Joint Medical Research Project of Chongqing Science and Technology Commission and Chongqing Health Commission(2024ZDXM005)
- DOI：10.16016/j.2097-0927.202501064
  CLC： R-332;R454.3;R684.05
- Received：23 January 2025，
  
  Revised：09 March 2025，
  
  Published：15 June 2025
- 稿件说明：
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唐秋雨，毛琳，白定群，等.低强度聚焦超声对大鼠膝关节僵硬的改善作用及机制研究［J］.陆军军医大学学报，2025，47（11）：1208-1216.DOI：10.16016/j.2097-0927.202501064.

TANG Q Y，MAO L，BAI D Q，et al.Therapeutic effect and underlying mechanism of low-intensity focused ultrasound on knee arthrofibrosis in rats［J］.J Army Med Univ，2025，47（11）：1208-1216.DOI：10.16016/j.2097-0927.202501064.
唐秋雨，毛琳，白定群，等.低强度聚焦超声对大鼠膝关节僵硬的改善作用及机制研究［J］.陆军军医大学学报，2025，47（11）：1208-1216.DOI：10.16016/j.2097-0927.202501064. DOI：

TANG Q Y，MAO L，BAI D Q，et al.Therapeutic effect and underlying mechanism of low-intensity focused ultrasound on knee arthrofibrosis in rats［J］.J Army Med Univ，2025，47（11）：1208-1216.DOI：10.16016/j.2097-0927.202501064. DOI：

摘要

目的

评估低强度聚焦超声（low-intensity focused ultrasound，LIFU）对大鼠膝关节僵硬中的疗效，并探究其发挥作用的潜在机制。

方法

选取购自重庆医科大学动物房的15只8周龄、体质量为250~300 g的SD雄性大鼠，按随机数字表法将其分为3组：空白对照组（

=5）、僵硬对照组（

=5）和僵硬超声组（

=5）。选取僵硬对照组和僵硬超声组大鼠建立膝关节僵硬模型，僵硬超声组行LIFU（频率1 MHz、功率1.5 W，20 min/次，5次/周）干预4周。分别于干预后第0、14、28天检测3组大鼠膝关节的屈伸活动度，并对其关节后囊进行组织学分析。分离培养大鼠膝关节原代滑膜成纤维细胞，根据是否进行TGF-β（10 ng/mL）诱导和LIFU干预，将其分为4组：空白对照组、LIFU组、TGF-β组及TGF-β+LIFU组，检测各组细胞纤维化相关指标及TGF-β/Smad通路表达的变化。

结果

在动物实验中，LIFU干预14 d时，僵硬超声组大鼠的膝关节屈伸活动度较僵硬对照组有所改善（

0.05），LIFU干预28 d时，僵硬超声组大鼠的膝关节屈伸活动度较僵硬对照组改善明显（

0.05）；同时，僵硬超声组大鼠膝关节后囊纤维化水平较僵硬对照组改善明显，纤维化相关指标（α-SMA，TGF-β）的表达水平下降（

0.05）。在细胞实验中，TGF-β组较空白对照组显著促进纤维化相关指标（α-SMA，COL1A1，COL3A1）蛋白和mRNA的表达（

0.05），并激活了TGF-β/Smad信号通路；而LIFU干预后，TGF-β+LIFU组较TGF-β组显著抑制TGF-β诱导的纤维化相关指标（α-SMA，COL1A1，COL3A1）的表达（

0.05）及TGF-β/Smad信号通路的激活。

结论

LIFU能够有效改善大鼠膝关节僵硬情况，其作用机制可能与抑制成纤维细胞活化及调控TGF-β/Smad信号通路有关。

Abstract

Objective To assess the therapeutic efficacy of low-intensity focused ultrasound (LIFU) on knee arthrofibrosis in rats and explore its underlying mechanisms. Methods Fifteen male SD rats (8 weeks old

weighing 250~300 g) were randomly divided into a blank control group

a model group

and an ultrasound treatment group

with 5 animals in each group. Rat model of knee joint stiffness was established in the model and ultrasound treatment group. The rats in the ultrasound group received LIFU intervention (frequency: 1 MHz

power: 1.5 W

20 min per session

5 times/week) for 4 weeks. The knee ran

ges of motion (ROM

flexion and extension) were measured in all 3 groups at 0

14 and 28 d after intervention. Histological analysis was conducted for the morphological changes in the posterior capsular area of the knee. After the synovial fibroblasts were primary isolated from rat knee joints

the cells were divided into blank control

LIFU

TGF-β (10 ng/mL)

and TGF-β+LIFU groups. Changes in fibrosis-related indicators and the TGF-β/Smad signaling pathway were assessed in each group. Results In the animal experiments

LIFU intervention for 14 d resulted in significantly improved flexion-extension ROM in knee joints when compared with the rats in the model group (

0.05)

and the improvement was more obvious at 28 d after intervention (P

0.05). After 28 d of LIFU intervention

the fibrosis of the posterior capsule of the knee joint was notably improved in the ultrasound group than the model group

and the expression levels of fibrosis-related indicators (α-SMA，TGF-β) were decreased (

0.05). In the cellular experiments

the TGF-β group exhibited remarkable up-regulation of fibrosis-related molecules (α-SMA，COL1A1，COL3A1) at both protein and mRNA levels (

0.05)

and activation of the TGF-β/Smad signaling pathway when compared to the blank control group. While LIFU intervention inhibited the expression of TGF-β-induced upregulation of fibrotic indicators (α-SMA，COL1A1，COL3A1) and the activation of TGF-β/Smad signaling pathway (

0.05).Conclusion‍　‍LIFU can effectively improve knee arthrofibrosis in rats

which potentially through the inhibition of fibroblast activation and modulation of the TGF-β/Smad signaling pathway.

关键词

Keywords

references

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