Effect of <i>Callicarpa nudiflora</i> on wound healing and PI3K/AKT/mTOR pathway by regulating M2 macrophage polarization in rats with diabetic foot ulcer

ZHANG Pan; WEI Yuanyuan; WANG Hao; WANG Xianwei; LI Yanqing; SUN Xue

doi:10.7619/jcmp.20243269

Journal of Clinical Medicine in Practice > 2025 > 29(4): 44-49, 54. > DOI: 10.7619/jcmp.20243269

ZHANG Pan, WEI Yuanyuan, WANG Hao, WANG Xianwei, LI Yanqing, SUN Xue. Effect of Callicarpa nudiflora on wound healing and PI3K/AKT/mTOR pathway by regulating M2 macrophage polarization in rats with diabetic foot ulcer[J]. Journal of Clinical Medicine in Practice, 2025, 29(4): 44-49, 54. DOI: 10.7619/jcmp.20243269

Citation:

PDF (1632 KB)

Effect of Callicarpa nudiflora on wound healing and PI3K/AKT/mTOR pathway by regulating M2 macrophage polarization in rats with diabetic foot ulcer

1.
Department of Laboratory Medicine, the Eighth People's Hospital of Hebei Province, Shijiazhuang, Hebei, 050000
2.
Department of Laboratory Medicine, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000
3.
Department of Microbiology, Dingzhou Center for Disease Control and Prevention, Baoding, Hebei, 071000
4.
Department of Laboratory Medicine, Shijiazhuang People's Hospital, Shijiazhuang, Hebei, 050000

More Information

Received Date: July 30, 2024
Revised Date: October 27, 2024

Graphical Abstract

Abstract

Abstract

Objective
To analyze the effect of Callicarpa nudiflora on wound healing and phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway by regulating M2 macrophage polarization in rats with diabetic foot ulcer.
Methods
A total of 40 rats were selected, with 10 rats in control group (topical application of saline), and the remaining 30 were used to establish rat model of diabetic foot ulcer. Ultimately, 27 rats were successfully modeled and divided into model group (topical application of saline), Callicarpa nudiflora group (topical application of Callicarpa nudiflora), and Callicarpa nudiflora combined with inhibitor group (topical application of Callicarpa nudiflora combined with CD206 inhibitor, a marker protein of M2 macrophages), with 9 rats in each group. The wound healing rate, levels of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), relative expression levels of inducible nitric oxide synthase (iNOS), CD16/32, CD206, PI3K, AKT and mTOR as well as mRNA expression levels of PI3K, AKT and mTOR were compared among groups.
Results
On the 3rd, 7th and 14th days after intervention, compared with the control group, the wound healing rate, VEGF, bFGF, relative expression level of CD206, relative expression of PI3K, AKT and mTOR at mRNA and protein levels were significantly decreased while the relative expression levels of iNOS and CD16/32 were significantly increased in all other groups (P < 0.05); compared with the model group, the Callicarpa nudiflora group and the Callicarpa nudiflora combined with inhibitor group showed significant increased wound healing rate, VEGF, bFGF, relative expression level of CD206, and relative expression of PI3K, AKT and mTOR at mRNA and protein levels, and significant decreased relative expression levels of iNOS and CD16/32 (P < 0.05); compared with the Callicarpa nudiflora group, the Callicarpa nudiflora combined with inhibitor group showed significant decreased wound healing rate, VEGF, bFGF, relative expression level of CD206, and relative expression of PI3K, AKT and mTOR at mRNA and protein levels, and significant increased relative expression levels of iNOS and CD16/32 (P < 0.05).
Conclusion
Callicarpa nudiflora can promote M2 macrophage polarization, increase wound healing rate and levels of VEGF and bFGF in rats with diabetic foot ulcer, and activate the PI3K/AKT/mTOR signaling pathway.
- Callicarpa nudiflora,
- M2 macrophage polarization,
- phosphatidylinositol-3-kinase,
- protein kinase B,
- mammalian target of rapamycin,
- diabetic foot,
- ulcer

FullText(HTML)

References (22)

References

[1]	CHAMBERLAIN R C, FLEETWOOD K, WILD S H, et al. Foot ulcer and risk of lower limb amputation or death in people with diabetes: a national population-based retrospective cohort study[J]. Diabetes Care, 2022, 45(1): 83-91. doi: 10.2337/dc21-1596
[2]	DE CASTRO J P W, FERREIRA F C, VARGAS J G F, et al. Accuracy of foot pressure measurement on predicting the development of foot ulcer in patients with diabetes: a systematic review and meta-analysis[J]. J Diabetes Sci Technol, 2023, 17(1): 70-78. doi: 10.1177/19322968211043550
[3]	王晓蓉, 李炳辉, 王知, 等. 脱细胞真皮基质对M1型巨噬细胞向M2型巨噬细胞转变的影响[J]. 中华实验外科杂志, 2022, 39(9): 1670-1673.
[4]	龚光明, 刘桠, 张翕宇, 等. 参芪复方调控PI3K/AKT/mTOR信号通路改善糖尿病GK大鼠胰岛功能减少血糖波动的实验研究[J]. 辽宁中医杂志, 2020, 47(9): 173-176.
[5]	张丽慧, 张震, 董婷婷, 等. 裸花紫珠胶囊联合头孢曲松钠治疗妊娠尿路感染的效果及对阴道微生态妊娠结局的影响[J]. 河北医学, 2022, 28(8): 1393-1399.
[6]	景亮, 祁永章. 红景天苷对糖尿病足溃疡大鼠Nrf2/Keap1信号通路及伤口愈合的影响[J]. 中国比较医学杂志, 2021, 31(8): 48-54.
[7]	黎珊珊, 区岛良, 张梅, 等. 大黄酚通过核因子E2相关因子2/血红素氧合酶-1信号通路对糖尿病足溃疡大鼠新生血管生成及氧化应激的影响[J]. 陕西医学杂志, 2023, 52(12): 1660-1664.
[8]	蓝羚升, 李莎, 黄晓飞. 下肢动脉病变程度对富血小板凝胶治疗糖尿病足溃疡的影响[J]. 实用临床医药杂志, 2024, 28(7): 106-109. doi: 10.7619/jcmp.20233516
[9]	程梅, 方朝晖, 程若东, 等. 超声清创术联合中药足浴对糖尿病足Wagner 2、3级溃疡的治疗效果[J]. 实用临床医药杂志, 2022, 26(17): 116-119. doi: 10.7619/jcmp.20221212
[10]	李吉庆, 林道斌, 张永杰, 等. 裸花紫珠调控IGF-1/PI3K/Akt信号通路对糖尿病足溃疡大鼠创面愈合的影响[J]. 中国老年学杂志, 2023, 43(6): 1458-1462.
[11]	张杰, 刘自新, 贾炳学, 等. 红花黄色素对糖尿病小鼠足溃疡创面愈合的影响及机制[J]. 新乡医学院学报, 2024, 41(5): 412-418.
[12]	LIU N, ZHANG J L, YIN M Z, et al. Inhibition of xCT suppresses the efficacy of anti-PD-1/L1 melanoma treatment through exosomal PD-L1-induced macrophage M2 polarization[J]. Mol Ther, 2021, 29(7): 2321-2334. doi: 10.1016/j.ymthe.2021.03.013
[13]	DAN H X, LIU S, LIU J J, et al. RACK1 promotes cancer progression by increasing the M2/M1 macrophage ratio via the NF-κB pathway in oral squamous cell carcinoma[J]. Mol Oncol, 2020, 14(4): 795-807. doi: 10.1002/1878-0261.12644
[14]	庞少博, 刘师伟, 段瑞雪, 等. Vaspin通过调控脂肪组织巨噬细胞极化改善2型糖尿病大鼠的胰岛素敏感性[J]. 中华内分泌代谢杂志, 2024, 40(2): 145-157.
[15]	孙志东, 高佳炜, 杨柳欣, 等. 基于miR-495/FTO通路介导的巨噬细胞极化探讨芪参汤改善胰岛素抵抗治疗2型糖尿病的分子机制[J]. 海南医学院学报, 2023, 29(14): 1075-1081.
[16]	臧宾宾, 李华, 杨颖, 等. 过表达SIRT1通过增强自噬水平调控巨噬细胞M2型极化减轻脓毒症诱导的急性肺损伤[J]. 中国免疫学杂志, 2023, 39(4): 698-703, 708.
[17]	PENG W X, HE P X, LIU L J, et al. LncRNA GAS5 activates the HIF1A/VEGF pathway by binding to TAF15 to promote wound healing in diabetic foot ulcers[J]. Lab Investig, 2021, 101: 1071-1083.
[18]	游敏, 杨丽, 袁丽, 等. 前列地尔联合硫辛酸对2型糖尿病足患者的临床疗效及对血清VEGF、bFGF、IGF-1、MMP-2和足背动脉血流动力学指标的影响[J]. 中国老年学杂志, 2020, 40(13): 2727-2730.
[19]	LI T T, HUANG H Q, ZHANG J L. The relationship between the levels of serum VEGF and bFGF and the degree of vascular disease of lower extremities in patients with diabetic foot[J]. Minerva Surg, 2023, 78(3): 339-341.
[20]	李恒, 寇谦, 周小茜. 通络疽愈方内服联合活血止痛洗剂对糖尿病足溃疡患者创面愈合程度、内皮生长因子及纤维蛋白原水平变化影响[J]. 辽宁中医药大学学报, 2020, 22(8): 85-89.
[21]	张亚兰, 马欣, 罗阳燕, 等. 利拉鲁肽通过磷酸肌醇3-激酶/蛋白激酶B/哺乳动物雷帕霉素靶蛋白通路对高糖诱导的人足细胞自噬及凋亡影响的研究[J]. 中国糖尿病杂志, 2024, 32(5): 380-388.
[22]	吴俊伟, 张越, 黄宝怡, 等. 基于PI3K/Akt/AS160/GLUT4通路探讨芪丹颗粒改善2型糖尿病大鼠胰岛素抵抗的作用机制[J]. 广州中医药大学学报, 2023, 40(12): 3123-3130.

[1]	YUAN Li, XIA Rongming, GAO Yueqiao, MIAO Xiufang. Analysis of early neuropsychological development in 417 premature infants and its influencing factors[J]. Journal of Clinical Medicine in Practice, 2022, 26(9): 103-106. DOI: 10.7619/jcmp.20214875
[2]	MA Linghua, LI Jiangheng, ZHONG Liuyu, HUANG Yongquan, ZHU Maoling. Clinical characteristics of pregnant woman in advanced maternal age and effect of pregnancy tests for pregnancy risks[J]. Journal of Clinical Medicine in Practice, 2022, 26(9): 50-53. DOI: 10.7619/jcmp.20214722
[3]	LIU Yangyang, YOU Yan, QIN Aiping, MA Min. A case analysis of fetal limb-body wall syndrome[J]. Journal of Clinical Medicine in Practice, 2022, 26(4): 127-129. DOI: 10.7619/jcmp.20212343
[4]	FU Ping, WU Wencui. Value of ultrasonic measurement of fetal fetal nuchal translucency thickness in early pregnancy and its relationship with adverse pregnancy outcomes[J]. Journal of Clinical Medicine in Practice, 2021, 25(15): 93-97. DOI: 10.7619/jcmp.20211030
[5]	LUO Aihua, BAO Rong, WU Tiantian, ZHU Jianlin. Value of color Doppler flow imaging combined with fetal non-stress test in diagnosis of fetal distress[J]. Journal of Clinical Medicine in Practice, 2020, 24(20): 100-102,107. DOI: 10.7619/jcmp.202020028
[6]	YIN Xiaohui, ZHOU Weihong, SUN Zhixia, XIA Jianmei, LI Ji, WANG Hua. Effect of real-time four-dimensional color Doppler ultrasonography on diangnosis of prenatal development of fetus[J]. Journal of Clinical Medicine in Practice, 2018, (22): 74-76. DOI: 10.7619/jcmp.201822024
[7]	LI Yunduan, LIU Weiwu, XU Xiuying. Multivariate analysis of fetal growth restriction and its prevention measures[J]. Journal of Clinical Medicine in Practice, 2017, (1): 90-93. DOI: 10.7619/jcmp.201701027
[8]	TIAN Ying. Effects of different feeding methods on neonatal development and maternal rehabilitation[J]. Journal of Clinical Medicine in Practice, 2016, (4): 127-129. DOI: 10.7619/jcmp.201604039
[9]	ZHAO Chunhua, WANG Yuqi. Influence of hyperbilirubinemia on neonatal nerve behavior and intellectual development[J]. Journal of Clinical Medicine in Practice, 2016, (3): 88-90,94. DOI: 10.7619/jcmp.201603027
[10]	CAO Hongzhen, BIAN Min, LI Qin, SHEN Jianqiu. Value of color Dopper ultrasonic examination in monitoring fetal renal artery blood flow parameters of patients with pregnancy-inducedhypertension syndrome and fetal growth restriction[J]. Journal of Clinical Medicine in Practice, 2014, (17): 94-96. DOI: 10.7619/jcmp.201417029

Cited By

Cited by

Periodical cited type(7)

1.	张考珍，严燕艺，商明，关换琼，张爱珍. 高龄孕妇再生育出生缺陷情况及其影响因素分析. 中外医学研究. 2022(10): 139-142 .
2.	孟远霞. 责任亲情交互护理模式干预在新生儿出生缺陷产妇中的应用效果及对产妇产后生活质量的影响. 临床医学研究与实践. 2021(04): 174-176+182 .
3.	罗丽兰，吴岸晓，王丽婷. 胎儿先天性畸形的调查结果统计及危险因素分析. 中国优生与遗传杂志. 2021(01): 107-110 .
4.	李淑妮，许晨耘，伍芳芳，蔡容燕，李春蕾，韩丽珍. 海口市2016—2019年新生儿出生缺陷情况及相关影响因素分析. 实用预防医学. 2021(07): 881-884 .
5.	章历红，赵灵. 高龄孕产妇孕前及孕期检查现状及影响因素分析. 中国计划生育学杂志. 2021(08): 1563-1567 .
6.	俞鹏，邓晓龙，袁军. 2017—2020年泰州市新生儿出生缺陷发生率调查及特征观察. 中国妇幼健康研究. 2021(09): 1245-1249 .
7.	刘清玲，刘长娣，杨舒. 胎儿发生先天性畸形的数据比例及影响因素的Logistic回归分析. 中国优生与遗传杂志. 2020(08): 1017-1019 .

Other cited types(3)

Get Citation

PDF

XML

Article views (28) PDF downloads (6) Cited by(10)

Turn off MathJax

Article Contents

Abstract

References

Effect of Callicarpa nudiflora on wound healing and PI3K/AKT/mTOR pathway by regulating M2 macrophage polarization in rats with diabetic foot ulcer