Investigation of Fasudil in its efficacy at improving flap innervation in mice

Xu Yidan, Wang yanting, Chen shaoFeng, Jing Xing, Xu Dan, Fangfang, Wang Hai, Xie Yun, Zhuang Yuehong

Chinese Journal of Clinical Anatomy ›› 2023, Vol. 41 ›› Issue (4) : 447-452.

PDF(8466 KB)
PDF(8466 KB)
Chinese Journal of Clinical Anatomy ›› 2023, Vol. 41 ›› Issue (4) : 447-452. DOI: 10.13418/j.issn.1001-165x.2023.4.13

Investigation of Fasudil in its efficacy at improving flap innervation in mice

  • Xu Yidan1, Wang yanting1, Chen shaoFeng2, Jing Xing2, Xu Dan2, Fangfang2, Wang Hai3, Xie Yun3, Zhuang Yuehong2*
Author information +
History +

Abstract

Objective    To explore whether Fasudil can promote the regeneration of the sensory nerve after flap surgery and its underlying mechanism.    Methods    92 ICR mice were selected and randomly divided into the control, Fasudil , LY294002, and Fasudil+LY294002 groups, and the corresponding drugs were injected intraperitoneally daily from 3d before surgery. At 0 d, 5 d, 7 d, 15 d and 30 d after operation, immunofluorescence staining was used to observe the axon outgrowth in the flap. The flap tissue at 5d after surgery was collected, and Western blotting was used to detect the expressions of RhoA, ROCK1+2, p-CPI-17, p-MYPT, p-PTEN, p-PI3K, and p-Akt in the flap. Secondly, rats 15d in pregnancy were adopted, the DRGs on both sides of the spinal cord were harvested and divided into 6 groups: the control, Fasudil, Fasudil+LY294002, CSPG, CSPG+Fasudil and CSPG+Fasudil+LY294002 groups. After 5d of culture, the axon lengths of the DRGss in the 6 groups were measured.    Results    Abundant nerve fibers could be observed in each group at 0d after operation; at 7d after operation, all nerve fibers underwent complete degeneration; at 15d and 30d after operation, only the Fasudil group had nerve fibers again. p-CPI-17 and p-MYPT in Fasudil group were down-regulated, and p-PI3K and p-Akt were up-regulated 5 days after operation (P<0.001). The average axon lengths of DRGs in the control, Fasudil, Fasudil+LY294002, CSPG, CSPG+Fasudil, and CSPG+Fasudil+LY294002 groups after 5d of culture were (1.96±0.24) mm, (2.73±0.30)mm, (2.07±0.13)mm, (1.62±0.20)mm, (2.35±0.13)mm, and (1.84±0.31)mm, respectively. The differences among the groups were statistically significant (P<0.001).    Conclusions    Fasudil promotes nerve regeneration in flap after surgery by inhibiting the RhoA/ROCK pathway and activating the PI3K/Akt pathway.

Key words

Flap /   /   / Nerve regeneration /   /   / Fasudil /   /   / RhoA/ROCK /   /   / PI3K/Akt

Cite this article

Download Citations
Xu Yidan, Wang yanting, Chen shaoFeng, Jing Xing, Xu Dan, Fangfang, Wang Hai, Xie Yun, Zhuang Yuehong. Investigation of Fasudil in its efficacy at improving flap innervation in mice[J]. Chinese Journal of Clinical Anatomy. 2023, 41(4): 447-452 https://doi.org/10.13418/j.issn.1001-165x.2023.4.13

References

[1] Scaglioni MF, Rittirsch D, Giovanoli P. Reconstruction of the heel, middle foot sole, and plantar forefoot with the medial plantar artery perforator flap: clinical experience with 28 cases[J]. Plast Reconstr Surg, 2018, 141(1) : 200-208 . DOI : 10.1097/PRS.0000000000003975.
[2] Kim JH, Rho YS, Ahn HY, et al. Comparison of sensory recovery and morphologic change between sensate and nonsensate flaps in oral cavity and oropharyngeal reconstruction[J]. Head Neck, 2008, 30(8) : 1099-1104. DOI : 10.1002/hed.20844.
[3]  郑一华, 穆兰花. 再造乳房皮瓣感觉恢复情况研究现状[J]. 整形再造外科杂志, 2006, 3(2 ) : 119-123. DOI: CNKI:SUN:ZZWK.0.2006-02-015.
[4] Vartanian ED, Lo AY, Hershenhouse KS, et al . The role of neurotization in autologous breast reconstruction: Can reconstruction restore breast sensation[J]. J Surg Oncol, 2021, 123(5): 1215-1231. DOI: 10.1002/jso.26422.  
[5]  张黎明, 肖婧. RhoA/ROCK通路在糖尿病大鼠心肌纤维化形成中的作用研究[J]. 临床和实验医学杂志, 2017, 16(11) : 1048-1050. DOI : 10.3969/j.issn.1671-4695.2017.11.003.
[6] Joshi AR, Bobylev I, Zhang G, et al. Inhibition of Rho-kinase differentially affects axon regeneration of peripheral motor and sensory nerves[J]. Exp Neurol, 2015, 263:28-38. DOI: 10.1016/j.expneurol. 2014.09.012. 
[7] J Chéret, N Lebonvallet, V Buhé, et al. Influence of sensory neuropeptides on human cutaneous wound healing process[J]. J Dermatol Sci, 2014, 74(3):193-203. DOI : 10.1016/j.jdermsci.2014. 02.001.
[8] Lähteenmäki T, Waris T, Asko-Seljavaara S, et al . Recovery of sensation in free flaps[J]. Scand J Plast Reconstr Surg Hand Surg, 1989, 23(3): 217-222. DOI: 10.3109/02844318909075121.
[9] Boyd B, Mulholland S, Gullane P, et al . Reinnervated lateral antebrachial cutaneous neurosome flaps in oral reconstruction: are we making sense[J]. Plast Reconstr Surg, 1994, 93(7): 1350-1362. DOI:10.1097/00006534-199406000-00004.
[10] Xie Y, Fang F, Su P, et al . Quantification of axonal ingrowth and functional recovery in a myocutaneous flap model in rats with strong clinical implications[J]. Wound Repair Regen, 2020,28(6) : 823-833.  DOI: 10.1111/wrr.12854. 
[11] Jaffe AB, Hall A . Rho GTPases: biochemistry and biology [J]. Annu Rev Cell Dev Biol, 2005, 21: 247-69. DOI: 10.1146/annurev.cellbio.21.020604.150721.
[12] He Z, Koprivica V. The Nogo signaling pathway for regeneration block[J]. Annu Rev Neurosci, 2004,27:341-68.  DOI: 10.1146/annurev.neuro.27.070203.144340.
[13] Zhou M, Li G, Zhu L, et al. Arctiin attenuates high glucose-induced human retinal capillary endothelial cell proliferation by regulating ROCK1/PTEN/PI3K/Akt/VEGF pathway in vitro[J]. J Cell Mol Med, 2020, 24(10):5695-5706. DOI: 10.1111/jcmm.15232.
PDF(8466 KB)

Accesses

Citation

Detail

Sections
Recommended

/