Abstract:
Objective To explore the effect of TaoHong Siwu decoction on rotator cuff tear in mice, so as to clarify its mechanism of the prevention and treatment in rotator cuff injury based on interleukin(IL)-4/ transcriptional activator protein (STAT)6.
Methods Fifty C57BL/6J mice were randomly divided into the control group, the rotator cuff injury group (model group), low, middle and high dose Taohong Siwu decoction groups with 10 mice in each group. Except for the control group, the rotator cuff tear reconstruction model was established in the other groups. The mice were fed with normal diet for 12 weeks and given the infection prevention treatment. After that, each mouse in the Taohong Siwu decoction group was intragastrically infused with corresponding solution each time, and the control group were given the same volume of normal saline every morning; the volume was 0.5 ml/20 g once per day, for the consecutive 12 weeks. Twenty-four hours after the last administration, the biomechanical stiffness of supraspinatus tendon was tested, the contents of serum nitric oxide synthase (iNOS), interleukin-6 (IL-6) and mannose receptor (cluster of differentiation 206, CD206) in mice were detected by enzyme-linked immunosorbent assay (ELISA). Real time PCR(RT-PCR) detected mRNA expressions of IL-1β, tumor necrosis factor(TNF)-α, IL-10, and inflammatory zone molecule 1 (Fizz1) in mouse tendon-bone interface tissue.Western Blot was used to detect iNOS, arginase-1 (Arg-1), IL-4, STAT6, and phosphorylation-STAT6 (p-STAT6) protein content. One-way ANOVA was used for comparison among multiple groups, and LSD-t test was used for pairwise comparison between groups.
Results After drug intervention, compared with the rotator cuff injury group, the tensile load and stiffness test values of each dose group of Taohong Siwu decoction were up-regulated (F=64.822, 58.431, both P<0.05); iNOS and IL-6 (M1 polarization marker) decreased (F=82.618, 61.372, both P<0.05), and CD206 (M2 polarization marker) increased (F=58.942, P<0.05). The expression sof IL-1β and TNF mRNA (M1 polarization marker) in the medium and high dose groups of Taohong Siwu decoction, were down-regulated (F=38.631, 33.714, both P<0.05), while the expressions of IL-10 and Fizz1 mRNA (M2 polarization marker) were up-regulated (F=41.731, 67.431, both P<0.05). The protein expressions of arg1, IL-4 and p-stat6 were up-regulated in low, medium and high dose groups of Taohong Siwu Decoction (F=26.841, 29.750, 26.863, all P<0.05).
Conclusion Taohong Siwu decoction can accelerate tendon remodeling in mice with rotator cuff tear, and its mechanism may be related to the regulation of macrophage polarization by IL-4/STAT6 signal pathway.
Key words:
Rotator cuff,
Macrophages
Jianfa Chen, Siwen Ma, Xiaobing Xiang. Mechanism of Taohong Siwu decoction regulating macrophage polarization on rotator cuff injury[J]. Chinese Journal of Joint Surgery(Electronic Edition), 2022, 16(03): 315-320.