厚朴酚通过调节SDF-1/CXCR4信号通路减轻LPS诱导的肾小球血管内皮细胞损伤-现代医学

厚朴酚通过调节SDF-1/CXCR4信号通路减轻LPS诱导的肾小球血管内皮细胞损伤

单位：1. 汉川市人民医院内科, 湖北汉川 431600;
2. 汉川市人民医院中医科, 湖北汉川 431600

分类号：R692.6

出版年·卷·期（页码）：2023·51·第九期（1292-1298）

摘要：

目的：研究厚朴酚对脂多糖(LPS)诱导的肾小球血管内皮细胞(GECs)损伤的影响以及基质细胞衍生因子-1(SDF-1)/趋化因子受体-4(CXCR4)信号通路的作用。方法：体外培养人肾小球血管内皮细胞(HRGEC)，将HRGEC分为正常组，模型组，厚朴酚-L、M、H组，厚朴酚+NUCC-390组共6组。除正常组外，其余组均用LPS诱导建立HRGEC损伤模型；CCK8法检测各组HRGEC增殖情况；流式细胞术检测各组HRGEC凋亡情况；酶联免疫吸附试验(ELISA)检测各组HRGEC上清液白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)水平；荧光定量聚合酶链反应(RT-PCR)检测各组HRGEC中SDF-1、CXCR4 mRNA水平；Western blot检测各组HRGEC的SDF-1、CXCR4、B淋巴细胞瘤-2(Bcl-2)、Bcl2相关X蛋白(Bax)蛋白水平。结果：与正常组比较，模型组HRGEC存活率降低、凋亡率升高，IL-6、TNF-α水平显著升高，SDF-1mRNA、CXCR4 mRNA、SDF-1蛋白、CXCR4蛋白、Bax蛋白表达水平显著升高，Bcl-2蛋白表达水平显著降低，差异均有统计学意义(均P<0.05)。与模型组比较，厚朴酚-L、M、H组HRGEC存活率升高、凋亡率降低，IL-6、TNF-α水平显著降低，SDF-1mRNA、CXCR4 mRNA、SDF-1蛋白、CXCR4蛋白、Bax蛋白表达水平显著降低，Bcl-2蛋白表达水平显著升高，且呈剂量依赖性，差异均有统计学意义(均P<0.05)。与厚朴酚-H组比较，厚朴酚+NUCC-390组HRGEC存活率降低、凋亡率升高，IL-6、TNF-α水平显著升高，SDF-1mRNA、CXCR4 mRNA、SDF-1蛋白、CXCR4蛋白、Bax蛋白表达水平显著升高，Bcl-2蛋白表达水平显著降低，差异均有统计学意义(均P<0.05)。结论：厚朴酚可能通过抑制SDF-1/CXCR4信号通路和HRGEC炎症反应、凋亡，而减轻LPS诱导的HRGEC损伤。

Objective: To study the impact of magnolol on lipolyaccharide(LPS)-induced glomerular endothelial cells(GECs) damage and the role of magnolol in stromal cell-derived factor-1(SDF-1)/CXC chemokine receptor 4(CXCR4) signaling pathway. Methods: Human glomerular endothelial cells(HRGEC) were cultured in vitro, and HRGEC was divided into six groups,namely normal group, model group, magnolol-L, M, H groups, and magnoliol+NUCC-390 group.Except normal group, the injury model of HRGEC was established by LPS induction in other groups. CCK8 method was applied to detect the proliferation of HRGEC in each group; flow cytometry was applied to detect the apoptosis of HRGEC in each group; enzyme linked immunosorbent assay(ELISA) was applied to detect the levels of interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) in the serum of each group;RT-PCR was applied to detect the levels of SDF-1 and CXCR4 mRNA in each group; Western blot was applied to detect the levels of SDF-1, CXCR4, B-cell lymphoma-2(Bcl-2), and Bcl2-associated X protein(Bax) in each group. Results: Compared with the normal group, the model group showed lower HRGEC survival rate, higher HRGEC apoptosis rate, the levels of IL-6, TNF-α and the expression of SDF-1 mRNA, CXCR4 mRNA, SDF-1, CXCR4, Bax increased, and the expression of Bcl-2 decreased, which were all statistically significant(all P<0.05). Compared with the model group, magnolol-L, M and H groups showed higher HRGEC survival rate, lower HRGEC apoptosis rate, the levels of IL-6, TNF-α and the expression of SDF-1 mRNA, CXCR4 mRNA, SDF-1, CXCR4, Bax decreased, and the expression of Bcl-2 increased, which were all in a dose-dependent manner.The differences were statistically significant(all P<0.05). Compared with magnolol-H group, magnoliol+NUCC-390 group showed lower HRGEC survival rate, higher HRGEC apoptosis rate, the levels of IL-6, TNF-α and the expression of SDF-1 mRNA, CXCR4 mRNA, SDF-1, CXCR4,Bax increased, and the expression of Bcl-2 decreased, which were all statistically significant(all P<0.05).Conclusion: Magnolol may inhibit the SDF-1/CXCR4 signaling pathway and the inflammatory response and apoptosis of HRGEC to alleviate LPS-induced HRGEC damage.

参考文献：

[1] FU J,YI Z,CAI M,et al.Global transcriptomic changes in glomerular endothelial cells in mice with podocyte depletion and glomerulosclerosis[J].Cell Death Dis,2021,12(7):687.
[2] MEDICA D,FRANZIN R,STASI A,et al.Extracellular vesicles derived from endothelial progenitor cells protect human glomerular endothelial cells and podocytes from complement-and cytokine-mediated injury[J].Cells,2021,10(7):1675.
[3] PANG X,MAO L,YE D,et al.Synthesis,anti-aging and mechanism of magnolol derivatives[J].Front Chem,2023,11:1180375.
[4] TANG C Y,LAI C C,HUANG P H,et al.Magnolol reduces renal ischemia and reperfusion injury via inhibition of apoptosis[J].Am J Chin Med,2017,45(7):1421-1439.
[5] 彭君,彭家清,秦鹏,等.和厚朴酚对高糖诱导的足细胞氧化应激及凋亡的影响[J].中国临床药理学杂志,2020,36(13):1870-1874.
[6] YANG T,LI C,LI Y,et al.MicroRNA-146a-5p alleviates the pathogenesis of osteoarthritis by inhibiting SDF-1/CXCR4-induced chondrocyte autophagy[J].Int Immunopharmacol,2023,117:109938.
[7] 王淑霞,王秀霞,宋彦峰.基于VEGFA/SDF-1/CXCR4通路探讨乌司他丁对脑卒中相关性肺炎大鼠肺组织的保护作用[J].现代医学,2022,50(8):946-952.
[8] CHANG H M,PENG K Y,CHAN C K,et al.FGF23 ameliorates ischemia-reperfusion induced acute kidney injury via modulation of endothelial progenitor cells:targeting SDF-1/CXCR4 signaling[J].Cell Death Dis,2021,12(5):409.
[9] 徐晨希,严浩军,刘芙蓉,等.参芪地黄汤含药血清对脂多糖诱导人肾小球内皮细胞损伤的保护作用及机制研究[J].中国中医药科技,2023,30(3):430-433.
[10] 王叶萍,李学琴,吴志刚,等.和厚朴酚抑制内毒素诱导的人肾小球系膜细胞炎症因子表达的研究[J].浙江中西医结合杂志,2011,21(2):77-80.
[11] 刘丽丽,吕立丽,谷雪.CXCR4靶向PI3K-Akt信号通路抑制小细胞肺癌血管生成[J].解放军医药杂志,2021,33(4):21-25.
[12] ANSERMET C,CENTENO G,NIKOLAEVA S,et al.The intrinsic circadian clock in podocytes controls glomerular filtration rate[J].Sci Rep,2019,9(1):16089.
[13] POLLAK M R,QUAGGIN S E,HOENIG M P,et al.The glomerulus:the sphere of influence[J].Clin J Am Soc Nephrol,2014,9(8):1461-1469.
[14] 陈碧霞,张利,吴玲玲,等.糖尿病肾病内皮细胞损伤机制的研究进展[J].解放军医学杂志,2020,45(8):876-883.
[15] ZHEN Y,FINKELMAN F D,SHAO W H.Mechanism of Mer receptor tyrosine kinase inhibition of glomerular endothelial cell inflammation[J].J Leukoc Biol,2018,103(4):709-717.
[16] 余婷,高原小雪,谢宇端,等.和厚朴酚通过miR-155靶向Smad3抑制高糖诱导肾小球系膜细胞凋亡的机制[J].中国老年学杂志,2021,41(24):5678-5682.
[17] 展俊平,孟庆良,孟婉婷,等.补阳还五汤对类风湿关节炎小鼠MPO,NE mRNA表达及TNF-α,IL-1β,IL-6,IL-17的影响[J].中国实验方剂学杂志,2018,24(24):158-163.
[18] 王延海,张雷明,冯艳艳.大黄素改善高糖条件中人肾小球血管内皮细胞炎症、氧化应激及凋亡作用的研究[J].中国临床药理学杂志,2023,39(10):1422-1426.
[19] PRIVRATSKY J R,IDE S,CHEN Y,et al.A macrophage-endothelial immunoregulatory axis ameliorates septic acute kidney injury[J].Kidney Int,2023,103(3):514-528.
[20] CAMPBELL K J,TAIT S W G.Targeting BCL-2 regulated apoptosis in cancer[J].Open Biol,2018,8(5):180002.
[21] GE G,ZHANG H,LI R,et al.The function of SDF-1-CXCR4 axis in SP cells-mediated protective role for renal ischemia/reperfusion injury by SHH/GLI1-ABCG2 pathway[J].Shock,2017,47(2):251-259.

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