Protective effects of salidroside on vascular endothelial cells in rats with frostbite after chronic hypoxia

doi:10.12047/j.cjap.6364.2022.121

Abstract

Abstract: Objective: To investigate the protective effects of salidroside on endothelial cells in rats with frostbite after chronic hypoxia. Methods: Healthy male SD rats, randomly divided into 3 groups with 10 rats in each group, which included the sham injury group, the model group, and the model +salidroside group. The rats in each group were placed in a composite low-pressure chamber to simulate a environment with a pressure of 54.1 kpa and a temperature of 23~25°C. The rats were exposed to hypoxia under these conditions for 14 days, during the experimental time the rats in the model+salidroside group were treated with 50 mg/kg salidroside daily. After the rats were removed from the low-pressure chamber, except for the sham injury group, frozen iron sheets were applied tightly to the back of the rats for 30 s, supplemented with low temperature for frostbite modeling. Blood and skin tissues were collected at 12 hours after modeling for testing. The structural changes in tissue and vascular endothelial cells were observed in the frostbite region. Vascular endothelial cell particulate EMP levels were detected. The levels of ICAM-1, sEPCR, vWF, ET-1 and NO secretion were determined. The expression levels of HIF-1α, p-PI3K, p-Akt and VEGF were detected by Western blot. Results: Salidroside could effectively reduce skin collapse in frostbitten areas. It could reduce the injury of frostbitten tissues, and improve the subcutaneous tissue necrosis and inflammatory cell infiltration. The autophagy of vascular endothelial cells was reduced. Compared with the model group (0.250±0.165)%, the expression of EMPs in the model+salidroside group (2.453±0.196)% was increased significantly (P＜0.01). In addition, the contents of NO (2.622±0.219)pg/ml was also significantly higher than that of the model group (1.616±0.152)pg/ml (P＜0.01), and the content of vWF (233.50±13.43)pg/ml was lower than that of the model group (315.60±8.78)pg/ml (P＜0.05). There was no significant difference in the levels of ICAM-1, sEPCR and ET-1. Salidroside significantly decreased the expressions of p-PI3K, p-Akt, VEGF and HIF-1α protein in vascular endothelial cells of rats with frostbite (P＜0.01). Conclusion: Salidroside can reduce endothelial cell damage, reduce endothelial cell autophagy and promote endothelial cell regeneration. Based on the PI3K/Akt pathway, salidroside has a good protective effect on endothelial cells of rats with frostbite after chronic hypoxia.

Key words: salidroside, frostbite, rats, vascular endothelial cell, EMPs, PI3K/Akt

CLC Number:

R751.05

WANG Hong-jin, LI Yi, FENG Yan-ping, ZHANG Ke-wei, PENG Mao-dong-zhi. Protective effects of salidroside on vascular endothelial cells in rats with frostbite after chronic hypoxia[J]. CJAP, 2022, 38(6): 664-669.

References

[1] 周淑蓉, 查选平, 林妹, 等. 应用CITE诊疗原则护理南方官兵赴北部寒区驻训冻伤的效果研究[J]. 海军医学杂志, 2022, 43(6): 565-568.
[2] Woo EK, Lee JW, Hur GY, et al. Proposed treatment protocol for frostbite: a retrospective analysis of 17 cases based on a 3-year single-institution experience[J]. Arch Plast Surg, 2013, 40(5): 510-516.
[3] Jiao M, Lou L, Jiao L, et al. Effects of low-frequency pulsed electromagnetic fields on plateau frostbite healing in rats[J]. Wound Repair Regen, 2016, 24(6): 1015-1022.
[4] 焦明克, 楼林, 胡劼, 等. 普通冻伤与高原冻伤血液微循环恢复的差异[J]. 解放军医学杂志, 2017, 42(1): 66-69.
[5] Mccauley RL, Heggers JP, Robson MC. Frostbite. Methods to minimize tissue loss[J]. Postgrad Med, 1990, 88(8): 67-68.
[6] Hayes DJ, Mandracchia VJ, Considine C, et al. Pentoxifylline. Adjunctive therapy in the treatment of pedal frostbite[J]. Clin Podiatr Med Surg, 2000, 17(4): 715-722.
[7] 黄钊. 高原低氧低温复合作用对大鼠血管内皮细胞的损伤及其防治作用的研究[D]. 天津体育学院, 2013.
[8] Yang A, Lu Y, Xing J, et al. IL-8 enhances therapeutic effects of BMSCs on bone regeneration via CXCR2-mediated PI3k/Akt signaling pathway[J]. Cell Physiol Biochem, 2018, 48(1): 361-370.
[9] 梁俊清, 徐海波, 陈小娟, 等. 通心络通过PI-3K/Akt/HIF信号通路改善血管内皮细胞缺氧损伤[J]. 中国病理生理杂志, 2012, 28(5): 846-851.
[10] 孙安琪, 颜天华, 巨修练. 红景天苷药理作用及分子机制的研究进展[J]. 时珍国医国药, 2018, 29(6): 1440-1443.
[11] Gordon C, Gudi K, Krause A, et al. Circulating endothelial microparticles as a measure of early lung destruction in cigarette smokers[J]. Am J Respir Crit Care Med, 2011, 184(2): 224-232.
[12] Moore GW, Semple JL. Freezing and frostbite on mount everest: new insights into wind chill and freezing times at extreme altitude[J]. High Alt Med Biol, 2011, 12(3): 271-275.
[13] Higdon B, Youngman L, Regehr M, et al. Deep frostbite treated with hyperbaric oxygen and thrombolytic therapies[J]. Wounds, 2015, 27(8): 215-223.
[14] Aizawa T. Reply: Protective effect of extract of Ginkgo biloba 761 against frostbite injury in rats[J]. Plast Reconstr Surg, 2020, 145(4): 874e-875e.
[15] 张涵, 陈海琪, 赖世龙, 等. 红景天苷对实验性高血压大鼠血管功能的影响[J]. 中国中医基础医学杂志, 2017, 23(1): 71-74.
[16] 王雪颖, 王世坤, 田铧, 等. 炎性环境下内皮微粒介导单核细胞促内皮细胞增殖的作用[J]. 解剖学报, 2012, 43(5): 614-618.
[17] 于治利, 关立克. 一氧化氮与血管内皮细胞功能障碍[J]. 吉林医学, 2011, 32(2): 318-320.
[18] Johansson J, Steinvall I, Herwald H, et al. Alteration of leukocyte count correlates with increased pulmonary vascular permeability and decreased PaO2:FiO2 ratio early after major burns[J]. J Burn Care Res, 2015, 36(4): 484-492.
[19] Damert A, Ikeda E, Risau W. Activator-protein-1 binding potentiates the hypoxia-induciblefactor-1-mediated hypoxia-induced transcriptional activation of vascular-endothelial growth factor expression in C6 glioma cells[J]. Biochem J, 1997, 327(Pt 2): 419-423.
[20] 张黎, 邱彦, 芮耀诚, 等. 缺氧对血管内皮生长因子诱导主动脉内皮细胞通透性增加的调控研究[J]. 药学实践杂志, 2004(3): 135-137.
[21] Lam MK, Al-Ansari S, van Dam GM, et al. Single-chain VEGF/Cy5.5 targeting vegf receptors to indicate atherosclerotic plaque instability[J]. Mol Imaging Biol, 2013, 15(3): 250-261.
[22] 孙改霞, 郭亚雄, 杜会博, 等. 失血性休克后的肠淋巴液提高血管通透性的作用[J]. 中国病理生理杂志, 2014, 30(8): 1506-1512.
[23] Jiang BH, Zheng JZ, Aoki M, et al. Phosphatidylinositol 3-kinase signaling mediates angiogenesis and expression of vascular endothelial growth factor in endothelial cells[J]. Proc Natl Acad Sci U S A, 2000, 97(4): 1749-1753.
[24] Mahendra G, Kumar S, Isayeva T, et al. Antiangiogenic cancer gene therapy by adeno-associated virus 2-mediated stable expression of the soluble FMS-like tyrosine kinase-1 receptor[J]. Cancer Gene Ther, 2005, 12(1): 26-34.
[25] Hennig B, Lei W, Arzuaga X, et al. Linoleic acid induces proinflammatory events in vascular endothelial cells via activation of PI3K/Akt and ERK1/2 signaling[J]. J Nutr Biochem, 2006, 17(11): 766-772.