吲哚丙酸通过调控NF-κB抑制LPS诱导的腹膜间皮细胞凋亡和炎症反应  

Indolepropionic acid inhibits LPS-induced apoptosis and inflammation of peritoneal mesothelial cells by regulating NF-κB

作　　者：李红波[1] 凃璨 付帅 姜南 丁艳琼[1] 熊飞[1] LI Hong-bo;TU Can;FU Shuai;JIANG Nan;DING Yan-qiong;XIONG Fei(Department of Nephrology,Wuhan No.1 Hospital,Wuhan 430022,China)

机构地区：[1]武汉市第一医院肾内科,武汉430022

出　　处：《现代免疫学》2025年第1期22-26,36,共6页Current Immunology

基　　金：武汉市卫健委医学科研项目(WX21B20)。

摘　　要：为探讨吲哚丙酸(indolepropionic acid,IPA)对LPS诱导的腹膜间皮细胞增殖、凋亡和炎症反应的影响及其机制,首先,分别用0.1、1.0、10μmol/L的IPA处理小鼠腹膜间皮细胞,24 h后用CCK-8法检测IPA的细胞毒性;其次,用0.1、1.0、10μmol/L的IPA预处理细胞2 h,再用10 mg/L的LPS处理24 h,用CCK-8法检测细胞增殖能力,以此确定IPA的最佳作用浓度。将细胞分成5组:对照组、LPS组、LPS+IPA组、LPS+QNZ(NF-κB通路抑制剂)组和LPS+QNZ+IPA组。用CCK-8法检测细胞增殖能力,流式细胞术检测细胞凋亡,ELISA检测细胞上清液中TNF-α的水平,Western blotting检测细胞中NF-κB p65和p-p65的表达。结果显示,0.1和1.0μmol/L的IPA对小鼠腹膜间皮细胞无细胞毒性,IPA最佳作用浓度为1.0μmol/L。与对照组比较,LPS组细胞增殖能力显著降低(P<0.01),细胞凋亡率、细胞上清液中TNF-α水平和细胞中NF-κB p65的磷酸化水平均显著升高(P<0.01);与LPS组比较,LPS+IPA组、LPS+QNZ组和LPS+QNZ+IPA组细胞增殖能力均显著升高(P<0.01),细胞凋亡率、细胞上清液中TNF-α水平和细胞中NF-κB p65的磷酸化水平均显著降低(P<0.05),其中LPS+QNZ+IPA组效果最显著。以上结果表明,IPA能够促进LPS诱导的小鼠腹膜间皮细胞增殖,抑制细胞凋亡和炎症反应,其机制可能与抑制NF-κB通路激活有关。The aim of this study is to investigate the effect and mechanism of indolepropionic acid(IPA)on LPS-induced proliferation,apoptosis,and inflammatory response of peritoneal mesothelial cells.Firstly,mouse peritoneal mesothelial cells were treated with 0.1,1.0,and 10μmol/L IPA,respectively.After 24 h,CCK-8 method was used to detect the cytotoxicity of IPA.Next,cells were pretreated with 0.1,1.0,and 10μmol/L IPA for 2 h,followed by treatment of 10 mg/L LPS for 24 h.CCK-8 method was used to detect the proliferation ability of cells,and the optimal working concentration of IPA was determined.The cells were divided into 5 groups:control group,LPS group,LPS+IPA group,LPS+QNZ(a NF-κB pathway inhibitor)group,and LPS+QNZ+IPA group.CCK-8 method was used to detect cell proliferation,and flow cytometry was used to detect cell apoptosis.ELISA was used to detect the level of TNF-αin the cell supernatant,and Western blotting was used to detect the expressions of NF-κB p65 and p-p65 in the cells.The results showed that 0.1 and 1.0μmol/L IPA had no cytotoxicity on mouse peritoneal mesothelial cells,and the optimal working concentration of IPA was 1.0μmol/L.Compared to those of control group,the proliferation ability of LPS group was significantly decreased(P<0.01),while the apoptosis rate,the level of TNF-αin the cell supernatant,and the phosphorylation level of NF-κB p65 in the cells were all significantly increased(P<0.01).Compared to that of the LPS group,the proliferation ability of LPS+IPA group,LPS+QNZ group,and LPS+QNZ+IPA group was significantly increased(P<0.01),while the apoptosis rate,the level of TNF-αin the cell supernatant,and the phosphorylation level of NF-κB p65 in the cells were significantly decreased(P<0.05).Therefore,LPS+QNZ+IPA combination showed the most significant effect.In summary,these results indicate that IPA promotes the proliferation of mouse peritoneal mesothelial cells induced by LPS,and inhibits cell apoptosis and inflammation.The underlying mechanism may be related to the inhibition of

关 键 词：吲哚丙酸 核因子ΚB 凋亡 炎症反应 

分 类 号：R572.2[医药卫生—消化系统] R967[医药卫生—内科学]