Effects of pirfenidone on nerve regeneration and functional recovery after sciatic nerve injury in rats

QI Jingtian; ZHANG Yongguang; XU Yongjun; SHENG Qingsong; CAI Longyu; YE Yongping

PDF(3337 KB)

Medical Journal of the Chinese People Armed Police Forces ›› 2025, Vol. 36 ›› Issue (2) : 124-128.

ORIGINAL ARTICLES

Effects of pirfenidone on nerve regeneration and functional recovery after sciatic nerve injury in rats

QI Jingtian¹, ZHANG Yongguang¹, XU Yongjun², SHENG Qingsong³, CAI Longyu¹, YE Yongping¹

Author information +

History +

Abstract

Objective To investigate the effect of pirfenidone on nerve regeneration in rats with sciatic nerve injury. Methods Rats with sciatic nerve injury were divided into four groups: normal saline group (control group, Ctrl), 25 mg/kg pirfenidone group (low-dose group, LG), 50 mg/kg pirfenidone group (medium-dose group, MG), and 100 mg/kg pirfenidone group (high-dose group, HG). An autograft repair model was established. The morphology of regenerative nerves was evaluated by electron microscopy (TEM). The recovery of motor function was assessed by Masson staining and sciatic functional index (SFI). The levels of transforming growth factor-β₁ (TGF-β₁) in regenerative nerves were determined by immunohistochemical staining. Results TEM results showed that the diameter of myelinated nerve fibers and the mean thickness of myelin sheath in the MG and HG groups were higher than those in the Ctrl and LG groups, and the G ratio were lower than those in the Ctrl and LG groups at 12 weeks after surgery. At both 8 and 12 weeks after surgery, the value of the percentage of gastrocnemius fibers and SFI in the MG and HG groups were significantly higher than those in the Ctrl and LG groups, and the differences were statistically significant(P<0.05). Immunohistochemical results indicated that TGF-β₁ expression in the MG and HG groups was significantly down-regulated compared with the Ctrl and LG groups, and the difference was statistically significant (P<0.05). Conclusions Pirfenidone can promote nerve regeneration and improve muscular function in rats with peripheral nerve injury, which may be related to its anti-fibrotic properties of pirfenidone.

Key words

pirfenidone / peripheral nerve injury / nerve scarring / nerve regeneration

Cite this article

EndNote

Ris (Procite)

Bibtex

Download Citations

QI Jingtian, ZHANG Yongguang, XU Yongjun, SHENG Qingsong, CAI Longyu, YE Yongping. Effects of pirfenidone on nerve regeneration and functional recovery after sciatic nerve injury in rats[J]. Medical Journal of the Chinese People Armed Police Forces. 2025, 36(2): 124-128

References

[1] Crosio A,Ronchi G,Fornasari B E,et al.Experimental methods to simulate and evaluate postsurgical peripheral nerve scarring[J]. J Clin Med,2021,10(8):1613.
[2] Guillamat-Prats R.The role of MSC in wound healing, scarring and regeneration[J].Cells,2021,10(7):1729.
[3] Aman M,Mayrhofer-Schmid M,Schwarz D,et al.Avoiding scar tissue formation of peripheral nerves with the help of an acellular collagen matrix[J].PLoS One,2023,18 (8):e0289677.
[4] Yılmaz M M,Akdere Ö E,Gümüşderelioglu M,et al.Biological nerve conduit model with de-epithelialized human amniotic membrane and adipose-derived mesenchymal stem cell sheet for repair of peripheral nerve defects[J].Cell Tissue Res, 2023,391 (3): 505-522.
[5] Duan G,Li C,Yan X,et al.Construction of a mineralized collagen nerve conduit for peripheral nerve injury repair[J].Regen Biomater,2023,10:89.
[6] Antar S A,Saleh M A,Al-Karmalawy A A.Investigating the possible mechanisms of pirfenidone to be targeted as a promising anti-inflammatory,anti-fibrotic,anti-oxidant, anti-apoptotic,anti-tumor,and/or anti-SARS-CoV-2[J]. Life Sci,2022,309: 121048.
[7] Boleto G,Avouac J,Allanore Y.The role of antifibrotic therapies in the treatment of systemic sclerosis-associated interstitial lung disease[J].Ther Adv Musculoskelet Dis,2022,14:175.
[8] Pan L,Meng F,Wang W,et al.Nintedanib in an elderly non-small-cell lung cancer patient with severe steroid-refractory checkpoint inhibitor-related pneumonitis: a case report and literature review[J].Front Immunol, 2023,13:1072612.
[9] Nakamura Y,Shimizu Y,Fujimaki-Shiraishi M,et al.A protective effect of pirfenidone in lung fibroblast-endothelial cell network via inhibition of rho-kinase activity[J].Biomedicines,2023,11(8):2259.
[10] Santacroce G,Lenti MV,Sabatino A.Therapeutic targeting of intestinal fibrosis in crohn's disease[J].Cells, 2022,11(3):429.
[11] Wong A Y,Scott J J.Functional recovery following direct or graft repair of nerve gaps in the rat[J]. Exp Neurol,1991,114(3):364-366.
[12] Terzis J,Faibisoff B,Williams B.The nerve gap:suture under tension vs. graft[J].Plast Reconstr Surg,1975,56 (2):166-170.
[13] Bain J R,Mackinnon S E,Hunter D A.Functional evaluation of complete sciatic,peroneal,and posterior tibial nerve lesions in the rat[J].Plast Reconstr Surg,1989,83(1):129-138.
[14] Wang R,Chen B,Wei H,et al.Collecting and deactivating TGF-β₁ hydrogel for anti-scarring therapy in post-glaucoma filtration surgery,materials today[J].Bio,2022,14:100260.
[15] Li Z, Yu S,Liu Y,et al.SU16f inhibits fibrotic scar formation and facilitates axon regeneration and locomotor function recovery after spinal cord injury by blocking the PDGFRβ pathway[J]J Neuroinflammation,2022,19(1): 95.
[16] Clifford T,Finkel Z,Rodriguez B,et al.Current advancements in spinal cord injury research-glial scar formation and neural regeneration[J].Cells,2023,12(6):853.
[17] Ying H,Fang M,Hang Q Q,et al.Pirfenidone modulates macrophage polarization and ameliorates radiation-induced lung fibrosis by inhibiting the TGF-β₁/Smad3 pathway[J].J Cell Mol Med,2021,25(18): 8662-8675.
[18] 韩晓强,梁泰刚,刘海波,等.抗转化生长因子β₁抗体对大鼠周围神经瘢痕中成纤维细胞增殖和胶原合成的影响[J].中国药物与临床, 2014,14(4):458-460.
[19] Lv Q,Wang J,Xu C,et al.Pirfenidone alleviates pulmonary fibrosis in vitro and in vivo through regulating Wnt/GSK-3β/β-catenin and TGF-β₁/Smad2/3 signaling pathways[J].Mol Med,2020,26(1):49.
[20] Qin Y,Cai M L,Jin H Z,et al.Age-associated B cells contribute to the pathogenesis of rheumatoid arthritis by inducing activation of fibroblast-like synoviocytes via TNF-α-mediated ERK1/2 and JAK-STAT1 pathways[J]. Ann Rheum Dis,2022,81(11):1504-1514.
[21] Beringer A,Miossec P.IL-17 and TNF-α co-operation contributes to the proinflammatory response of hepatic stellate cells[J].Clin Exp Immunol,2019,198 (1):111-120.
[22] Li Y,Zhao J,Yin Y,et al.The role of il-6 in fibrotic diseases: molecular and cellular mechanisms[J]. Inter J Bio Sci,2022,18(14):5405-5414.