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  

Magnolol alleviates LPS-induced glomerular endothelial cells damage by regulating the SDF-1/CXCR4 signaling pathway

作　　者：陈泽[1] 曾进军 CHEN Ze;ZENG Jinjun(Department of Internal Medicine,Hanchuan People's Hospital,Hanchuan 431600,China;Department of Traditional Chinese Medicine,Hanchuan People's Hospital,Hanchuan 431600,China)

机构地区：[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

出　　处：《现代医学》2023年第9期1292-1298,共7页Modern Medical Journal

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-αand 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-αand 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-αand 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 signalin

关 键 词：厚朴酚 基质细胞衍生因子-1/趋化因子受体-4 脂多糖 肾小球血管内皮细胞 

分 类 号：R692.6[医药卫生—泌尿科学]