Objective: Through clinical trials, this study observes the therapeutic effect of platelet-rich plasma (platelet-rich plasma, PRP) on diabetic foot ulcers and explored the relationship between the relationship between PRP and autophagy. Methods: Thirty patients with diabetic foot ulcer who met the relevant criteria were randomly divided into PRP treatment group and control group. In the PRP treatment group, the formed PRP gel was coated and bandaged on the diabetic foot ulcer wound, and the PRP treatment was repeated on the seventh day. The control group was covered with normal saline sterile gauze. Observe the healing rate of the wound in 7 days, 14 days and 21 days, the pain in 5 consecutive days and the healing time of the wound after treatment, collect wound granulation tissues before and twenty-first days after treatment then detect the expression of autophagy-related proteins (LC-3, P62) and inflammatory factors (IL-6, IL-10) in diabetic foot ulcer wound to investigate the potential relationship between PRP treatment of diabetic foot ulcers and autophagy and inflammatory responses. Results: The wound healing rate of diabetic foot ulcer patients in the PRP treatment group was higher than that in the control group on the seventh, 14th and 21st days, the healing time (31.40 ± 4.47) was better than that in the control group (43.20 ± 5.03) days, and the pain improvement was better than that in the control group (P < .05). The results of Western blot analysis and quantitative PCR of autophagy-related proteins (LC-3 and p62) in granulation tissue showed that the values of LC3 and LC3-II/LC3-I and the expression of LC3 gene in wound granulation tissue of PRP group were significantly higher than those before treatment (P < .05). The value and gene expression of P62 protein were lower than those before treatment (P < .05). In the control group, there was no significant difference in LC3 and P62 protein gray level and gene expression before and after treatment (P > .05). The level of autophagy in the wound of PRP group increased after treatment, while there was no statistical significance in the control group. The results of ELISA showed that the concentration of IL-6 in granulation tissue of the PRP treatment group was lower than that before treatment (P < .05), while there was no significant difference in IL-6 in the control group after treatment. The concentration of IL-10 increased in both groups after treatment, but the concentration in PRP group was higher than that in control group (P < .05). Conclusions: This study shows that PRP gel has advantages in accelerating wound healing, relieving pain, shortening healing time and reducing inflammatory response in treating diabetic foot ulcers wound, which may be related to autophagy, and provides new ideas for the treatment of diabetic foot ulcers.
XuYWangLHeJ, et al. Prevalence and control of diabetes in Chinese adults[J]. JAMA.2013;310(9):948‐959.
2.
MusuuzaJSutherlandBLKurterS, et al. A systematic review of multidisciplinary teams to reduce major amputations for patients with diabetic foot ulcers[J]. J Vasc Surg.2020;71(4):1433‐1446.e3.
3.
ElMCosiallsEMehrpourM, et al. Crosstalk between autophagy and metabolic regulation of cancer stem cells[J]. Mol Cancer.2020;19(1):27.
4.
FanYZhaoXLuK, et al. LncRNA BDNF-AS promotes autophagy and apoptosis in MPTP-induced Parkinson’s disease via ablating microRNA-125b-5p[J]. Brain Res Bull.2020 Apr;157:119‐127. doi:10.1016/j.brainresbull.2020.02.003.
5.
DongYChenHGaoJ, et al. Molecular machinery and interplay of apoptosis and autophagy in coronary heart disease[J]. J Mol Cell Cardiol.2019 Nov;136:27‐41. doi:10.1016/j.yjmcc.2019.09.001.
6.
BuglianiMMossutoSGranoF, et al. Modulation of autophagy influences the function and survival of human pancreatic beta cells under endoplasmic Reticulum stress conditions and in type 2 diabetes[J]. Front Endocrinol (Lausanne).2019 Feb 26;10:52. doi:10.3389/fendo.2019.00052.
7.
RenH, Zhao F, Zhang Q, et al. Autophagy and skin wound healing. Burns Trauma.2022 Feb 16;10:tkac003. doi:10.1093/burnst/tkac003.
8.
ParkSYShresthaSYounYJ, et al. Autophagy primes neutrophils for neutrophil extracellulartrap formation during sepsis. Am J Respir Crit Care Med. 2017 Sep 1;196(5):577-589. doi:10.1164/rccm.201603-0596OC.
9.
ZhangJZhangCJiangX, et al. Involvement of autophagy in hypoxia-BNIP3 signaling to promote epidermal keratinocyte migration. Cell Death Dis. 2019 Mar 8;10(3):234. doi:10.1038/s41419-019-1473-9.
10.
AnY, Liu WJ, Xue P, et al. Autophagy promotes MSC-mediated vascularization in cutaneous wound healing via regulation of VEGF secretion. Cell Death Dis.2018;9(2):58.
11.
HanYFSunTJHanYQ, et al. Clinical perspectives on mesenchymal stem cells promoting wound healing in diabetes mellitus patients by inducing autophagy[J]. Eur Rev Med Pharmacol Sci.2015;19(14):2666‐2670.
12.
JinHZhangZWangC, et al. Melatonin protects endothelial progenitor cells against AGE-induced apoptosis via autophagy flux stimulation and promotes wound healing in diabetic mice[J]. Exp Mol Med.2018;50(11):154.
13.
DelPTTrujilloMAndiaI, et al. Platelet-rich plasma for the treatment of diabetic foot ulcers: A meta-analysis[J]. Wound Repair Regen.2019;27(2):170‐182.
14.
LiTMaYWangM, et al. Platelet-rich plasma plays an antibacterial, anti-inflammatory and cell proliferation-promoting role in an in vitro model for diabetic infected wounds[J]. Infect Drug Resist. 2019 Jan 29;12:297-309. doi:10.2147/IDR.S186651.
15.
MoussaMLajeunesseDHilalG, et al. Platelet rich plasma (PRP) induces chondroprotection via increasing autophagy, anti-inflammatory markers, and decreasing apoptosis in human osteoarthritic cartilage[J]. Exp Cell Res.2017;352(1):146‐156.
16.
YangFHuHYinW, et al. Autophagy is independent of the chondroprotection induced by platelet-rich plasma releasate[J]. Biomed Res Int. 2018 Jul 24;2018:9726703. doi:10.1155/2018/9726703.
17.
YangLTLiLHPengWN. Platelet rich plasma alleviates OGD/R injury in N2a cell by enhancing autophagy through the miR223/PAQR3 pathway. Acta Neurobiol Exp (Wars).2022;82(2):121‐132.
18.
ShahP, Inturi R, Anne D, et al. Wagner’s classification as a tool for treating diabetic foot ulcers: Our observations at a suburban teaching hospital. Cureus.2022;14(1):e21501.
19.
DelPTTruMMAndiaI, et al. Platelet-rich plasma for the treatment of diabetic foot ulcers: A meta-analysis[J]. Wound Repair Regen.2019;27(2):170‐182.
20.
MorimotoNKakudoNMatsuiM, et al. Exploratory clinical trial of combination wound therapy with a gelatin sheet and platelet-rich plasma in patients with chronic skin ulcers: Study protocol[J]. BMJ Open.2015;5(5):e007733.
21.
JanisJEHarrisonB. Wound healing: Part I. Basic science. Plast Reconstr Surg [J].2016;138(3 Suppl):9S‐17S.
22.
AumillerWDDollahiteHA. Pathogenesis and management of diabetic foot ulcers[J]. JAAPA.2015;28(5):28‐34.
23.
LiaoHTMarraKGRubinJP. Application of platelet-rich plasma and platelet-rich fibrin in fat grafting: Basic science and literature review[J]. Tissue Eng Part B Rev.2014;20(4):267‐276.
24.
Cieslik-BieleckaABoldTZiółkowskiG, et al. Antibacterial activity of leukocyte- and platelet-rich plasma: An in vitro study[J]. Biomed Res Int. 2018 Jun 27;2018:9471723. doi:10.1155/2018/9471723.
25.
CetinkayaRAYenilmezEPetroneP, et al. Platelet-rich plasma as an additional therapeutic option for infected wounds with multi-drug resistant bacteria: In vitro antibacterial activity study[J]. Eur J Trauma Emerg Surg.2019;45(3):555‐565.
26.
DhamodharanU, Viswanathan V, Krishnamoorthy E, et al. Genetic association of IL-6, TNF-alpha and SDF-1 polymorphisms with serum cytokine levels in diabetic foot ulcer. Gene.2015;565(1):62‐67.
27.
JiangTXZouJBZhuQQ, et al. SIP/CacyBP promotes autophagy by regulating levels of BRUCE/apollon, which stimulates LC3-I degradation[J]. Proc Natl Acad Sci U S A.2019;116(27):13404‐13413.
28.
YimWWMizushimaN. Lysosome biology in autophagy[J]. Cell Discov. 2020 Feb 11;6:6. doi:10.1038/s41421-020-0141-7.
29.
SaraivaMVieiraPO’GarraA. Biology and therapeutic potential of interleukin-10[J]. J Exp Med.2020;217(1):e20190418.
30.
QianMFangXWangX. Autophagy and inflammation[J]. Clin Transl Med.2017;6(1):24.
31.
WuTTLiWMYaoYM. Interactions between autophagy and inhibitory cytokines[J]. Int J Biol Sci.2016;12(7):884‐897.
