大蒜素通过异质核核糖核蛋白K调控细胞焦亡改善大鼠肝纤维化的机制研究  

Mechanistic study on the improvement of rat liver fibrosis by allicin through the regulation of pyroptosis via heterogeneous nuclear ribonucleoprotein K

作　　者：王磊 郑广涛 仲春雪 冀伟 寇巧春 WANG Lei;ZHENG Guangtao;ZHONG Chunxue;JI Wei;KOU Qiaochun(Department of Gastrointestinal Surgery,the Fifth Affiliated Hospital of Xinjiang Medical University,Urumqi 830000,China)

机构地区：[1]新疆医科大学第五附属医院胃肠外科,新疆乌鲁木齐830000

出　　处：《胃肠病学和肝病学杂志》2024年第11期1494-1500,共7页Chinese Journal of Gastroenterology and Hepatology

基　　金：新疆维吾尔自治区自然科学基金(2021D01C425)。

摘　　要：目的探讨异质核核糖核蛋白K(heterogeneous nuclear ribonucleoprotein K,hnRNPK)在大蒜素治疗肝纤维化中的潜在作用机制。方法分别收集2021年12月至2022年12月于我院接受治疗的10例肝纤维化患者及10名健康对照人群中的外周血样本。检测hnRNPK及细胞焦亡相关蛋白的表达。随后建立敲降hnRNPK的大鼠肝纤维化模型,并给予大蒜素治疗。HE和Masson染色检测肝组织的炎症、结构及纤维化改变;免疫组化检测hnRNPK的表达;RT-qPCR和Western blotting检测hnRNPK及细胞焦亡相关蛋白的表达;ELISA检测炎症因子的水平。结果与对照组比较,肝纤维化患者中hnRNPK、NLRP3、Caspase-1、GSDMD、IL-1β和IL-18的表达均显著升高(P<0.05)。大鼠肝纤维化模型的肝组织中有明显的炎性细胞浸润、纤维化和hnRNPK的表达,在大蒜素治疗后肝组织中的炎症、纤维化及hnRNPK的表达均降低。与对照组比较,大鼠肝纤维化模型中hnRNPK、NLRP3、Caspase-1、GSDMD、Cleaved-Caspase-3、IL-1β和IL-18的表达均显著升高,Caspase-3表达下降(P<0.05);与模型组比较,大蒜素治疗组和hnRNPK敲降组大鼠中hnRNPK、NLRP3、Caspase-1、GSDMD、Cleaved-Caspase-3、IL-1β和IL-18的表达均显著降低,Caspase-3表达升高(P<0.05)。结论大蒜素可能通过降低hnRNPK的表达抑制细胞焦亡信号,进而在肝纤维化中发挥抑制炎症和纤维化的作用。Objective To investigate the potential mechanism of action of heterogeneous nuclear ribonucleoprotein K(hnRNPK)in the treatment of liver fibrosis with allicin.Methods Peripheral blood samples were collected from 10 patients with liver fibrosis who received treatment at our hospital and 10 control individuals from Dec.2021 to Dec.2022.The expression of hnRNPK and pyroptosis-related proteins was examined.Subsequently,a rat model of liver fibrosis with hnRNPK knockdown was established and treated with allicin.Inflammation,structural changes,and fibrotic alterations in liver tissues were assessed using HE and Masson staining;the expression of hnRNPK was detected using immunohistochemistry.The expression of hnRNPK and pyroptosis-related proteins was measured by using RT-qPCR and Western blotting;and the levels of inflammatory factors were evaluated by using ELISA.Results Compared to the control group,the expression of hnRNPK,NLRP3,Caspase-1,GSDMD,IL-1β and IL-18 was significantly increased in patients with liver fibrosis(P<0.05).In the rat model of liver fibrosis,liver tissues showed evident inflammatory cell infiltration,elevated fibrosis levels,and hnRNPK expression.After allicin treatment,inflammation,fibrosis,and hnRNPK expression in the liver tissues were reduced.Compared to the control group,the expression of hnRNPK,NLRP3,Caspase-1,GSDMD,Cleaved-caspase-3,IL-1β and IL-18 was significantly increased in the rat liver fibrosis model,while Caspase-3 expression decreased(P<0.05).Compared to the model group,in the allicin treatment group and the hnRNPK knockdown group of rats,the expression of hnRNPK,NLRP3,Caspase-1,GSDMD,Cleaved-caspase-3,IL-1β and IL-18 was significantly reduced,while Caspase-3 expression increased(P<0.05).Conclusion Allicin may exert its anti-inflammatory and anti-fibrotic effects in liver fibrosis by inhibiting the pyroptotic signaling through the reduction of hnRNPK expression.

关 键 词：肝纤维化 hnRNPK 细胞焦亡 纤维化 炎症 

分 类 号：R575[医药卫生—消化系统]