吲哚丙酸通过促进调节性T细胞水平减轻硫代乙酰胺诱导的急性肝损伤  

Indolepropionic acid alleviates thioacetamide induced acute liver injury by promoting regulatory T cell levels

作　　者：周波 阮一 朱宏达 杨勇[1] 杨沔[1] ZHOU Bo;RUAN Yi;ZHU Hongda;YANG Yong;YANG Mian(Ningbo Medical Centre Lihuili Hospital,Ningbo 315040,Zhejiarng,China)

机构地区：[1]宁波市医疗中心李惠利医院,宁波315040

出　　处：《现代实用医学》2024年第5期576-581,共6页Modern Practical Medicine

基　　金：浙江省医药卫生科技计划项目(2021KY1036);宁波市科技计划项目(2023J231)。

摘　　要：目的 探讨吲哚丙酸(IPA)减轻硫代乙酰胺(TAA)诱导急性肝损伤(ALI)的潜在机制,并分析调节性T细胞(Treg)在其中发挥的作用。方法 将SPF级雄性C57BL/6小鼠按随机数表法分为对照组(注射0.9%氯化钠注射液)、TAA组(TAA 100 mg/kg腹腔注射)、IPA组(TAA建模后IPA 20 mg/kg灌胃),每组10只。24 h后取小鼠血清和肝组织,ELISA法检测各组丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转氨酶(AST)、干扰素-γ(IFN-γ)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、IL-6、转化生长因子-β(TGF-β)及IL-10的水平,病理学鉴定肝损伤情况,免疫组织荧光检测肝内Treg水平。体外实验获取小鼠脾脏并分选幼稚T细胞(Na?veT)诱导Treg,培养过程加入IPA,ELISA检测处理后的TGF-β、IL-10及相对RNA表达水平。结果IPA能显著降低TAA诱导的ALI水平,IPA组ALT、AST及病理评分(Suzuki)明显低于TAA组,免疫荧光显示IPA组肝内表现更高的Treg水平(均P <0.05)。ELISA检测结果显示IPA组小鼠肝脏促炎因子IFN-γ、TNF-α、IL-1β、IL-6显著下降,抑炎因子TGF-β、IL-10水平明显上调(均P <0.05)。体外实验显示IPA能促进Treg分化并表达更高的叉状头转录因子3(Foxp3)水平,同时促进抑炎因子TGF-β、IL-10分泌及相应RNA表达。结论IPA通过促进Treg的分化及抑炎因子TGF-β、IL-10分泌,调节肝内免疫平衡,抑制肝内炎性反应进而减轻TAA诱导的ALI。Objective To investigate the potential mechanisms of indolepropionic acid(IPA)in mitigating thioac-etamide(TAA)-induced acute liver injury,and ananlyze the role of regulatory T cells(Treg)in this process.Methods SPF-grade male C57BL/6 mice were randomly divided into a control group(injected with saline),a TAA group(TAA 100 mg/kg intraperitoneal injection),and an IPA group(TAA-induced model followed by IPA 20 mg/kg ga-vage),with ten mice in each group.Mouse serum and liver tissues were collected after 24 hours.alanine aminotrans-ferase(ALT),aspartate aminotransferase(AST),pro-inflammatory factors[interferon(IFN-),tumor necrosis factor(TNF-),interleukin(IL)-1,IL-6],and anti-inflammatory factors[transforming growth factor(TGF-),IL-10]levels were measured by ELISA.Liver injury was assessed by histologically,and liver resident Treg levels were detected by immunofluorescence.In vitro,mice spleen was obtained and Naïve T cells(Naïve T)were selected to induce Treg.IPA was added during the culture process to explore its effect on Treg differentiation.ELISA was used to measure the secretion levels of anti-inflammatory factors TGF-,IL-10 and the corresponding RNA expression levels.Results IPA significantly reduced TAA-induced acute liver injury.Liver function index ALT,AST,and pathological scores in the IPA group were significantly lower than those in the TAA group(all<0.05).Immunofluorescence revealed higher level of Treg in the liver of the IPA group(<0.05).ELISA results showed that pro-inflammatory factors IFN-,TNF-,IL-1,IL-6 in the liver of mice in the IPA group significantly decreased,while anti-inflammatoryfactors TGF-,IL-10 levels significantly increased(all<0.05).In vitro experiments showed that IPA promoted Treg dif-ferentiation and expressed higher levels of Foxp3,as well as promoting the secretion and corresponding RNA ex-pression of anti-inflammatory factors TGF-,IL-10.Conclusions IPA alleviated TAA induced acute liver injury by promoting the differentiation of Treg and the anti-inflammatory factor(TGF-,IL-10)

关 键 词：吲哚丙酸 调节性T细胞 硫代乙酰胺 肝损伤 

分 类 号：R657.3[医药卫生—外科学]