三叶香茶菜提取物对肝星状细胞和肝细胞TLR4/NF-κB/NLRP3通路的影响
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篇名: 三叶香茶菜提取物对肝星状细胞和肝细胞TLR4/NF-κB/NLRP3通路的影响
TITLE: Effects of Isodon ternifolius extract on TLR 4/NF-κB/NLRP3 pathway in hepatic stellate cells and hepatocytes
摘要: 目的 探讨三叶香茶菜提取物对肝星状细胞和肝细胞Toll样受体4(TLR4)/核因子κB(NF-κB)/NOD样受体蛋白3(NLRP3)通路的影响。方法以大鼠原代肝星状细胞和原代肝细胞为对象,以脂多糖(LPS,100ng/mL)诱导建立炎性损伤模型,以秋水仙碱(1μmol/L)为阳性对照,以TLR4阻断剂(TAK-242,1μmol/L)为参照,检测经三叶香茶菜提取物(1mg/mL,以生药量计)干预后肝星状细胞上清液中转化生长因子β(1TGF-β1)、α-平滑肌肌动蛋白(α-SMA)、Ⅰ型胶原(COL-Ⅰ)、COL-Ⅲ和肝细胞上清液中丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、白细胞介素1β(IL-1β)、IL-18的含量,以及2种细胞中TLR4、核因子κB抑制蛋白α(IκBα)、NF-κBp65、NLRP3、GasderminD(GSDMD)、凋亡相关微粒蛋白(ASC)mRNA和TLR4、磷酸化IκBα(p-IκBα)、NF-κBp65、NLRP3、GSDMD、ASC蛋白的表达情况。结果与LPS模型组比较,各药物组肝星状细胞上清液中TGF-β1、α-SMA、COL-Ⅰ、COL-Ⅲ和肝细胞上清液中ALT、AST、IL-1β、IL-18的含量,以及2种细胞中TLR4、NF-κBp65、NLRP3、GSDMD、ASCmRNA和TLR4、p-IκBα、NF-κBp65、NLRP3、GSDMD、ASC蛋白的表达均显著降低或下调,IκBαmRNA的表达均显著上调(P<0.05);与TLR4阻断剂组比较,TLR4阻断剂+三叶香茶菜提取物组上述多数指标的改善更加明显(P<0.05)。结论三叶香茶菜提取物能通过抑制TLR4/NF-κB/NLRP3通路活化,减少纤维因子、炎症因子释放,减轻肝细胞炎性损伤,抑制肝星状细胞活化,从而发挥保护肝细胞、抗肝纤维化的作用。
ABSTRACT: OBJECTIVE To investigate the effects of Isodon ternifolius extract on Toll -like receptor 4(TLR4)/nuclear factor - κB(NF-κB)/NOD-like receptor protein 3(NLRP3)pathway in hepatic stellate cells and hepatocytes . METHODS Using primary hepatic stellate cells and primary hepatocytes of rats as subjects ,inflammatory injury model was induced by lipopolysaccharide (LPS,100 ng/mL). Using colchicine (1 μmol/L)as positive control and TLR 4 inhibitor(TAK-242,1 μmol/L)as reference ,the contents of transforming growth factor -β1(TGF-β1),α-smooth muscle actin (α-SMA),type Ⅰ collagen(COL-Ⅰ),COL-Ⅲ in the supernatant of hepatic stellate cells ,and the contents of alanine aminotransferase (ALT),aspartate aminotransferase (AST),interleukin-1β (IL-1β) and IL -18 in the supernatant of hepatocytes were detected after intervention with I. ternifolius extract(1 mg/mL). The mRNA expressions of TLR 4,inhibitor α of NF -κB(IκBα),NF-κB p 65,NLRP3,Gasdermin D (GSDMD),apoptosis-associated speck -like protein containing CARD (ASC) and protein expressions of TLR 4, phosphorylated I κBα(p-IκBα),NF-κB p 65,NLRP3,GSDMD,ASC in the above cells were determined . RESULTS Compared with LPS model group ,the contents of TGF -β1,α-SMA, COL-Ⅰ and COL -Ⅲ in the supernatant of hepatic stellate cells and the contents of ALT ,AST,IL-1β and IL -18 in the supernatant of hepatocytes were significantly decreased ;the mRNA expressions of TLR 4,NF-κB p 65,NLRP3,GSDMD,ASC and the protein expressions of TLR 4,p-IκBα,NF-κB p 65,NLRP3,GSDMD,ASC in the two kinds of cells were significantly down - regulated,and the mRNA expression of I κBα was significantly up -regulated in all administration groups (P<0.05). Compared with TLR 4 inhibitor group ,the improvement of most of above indexes was more significant in the TLR 4 inhibitor+I. ternifolius extract group (P<0.05). CONCLUTIONS I. ternifolius extract could inhibit the activation of TLR 4/NF-κB/NLRP3 pathway, reduce the release of fibrosis factors and inflammatory factors ,alleviate the inflammatory injury of liver cells ,and inhibit the activation of hepatic stellate cells ,so as to protect liver cells and resist liver fibrosis .
期刊: 2022年第33卷第20期
作者: 覃乐,陈勇,黄桂东,吴瑞胜,刘代华,周至品
AUTHORS: QIN Le,CHEN Yong,HUANG Guidong,WU Ruisheng,LIU Daihua,ZHOU Zhipin
关键字: 三叶香茶菜提取物;肝星状细胞;肝细胞;TLR4/NF-κB/NLRP3通路;肝纤维化;炎症反应
KEYWORDS: Isodon ternifolius extract;hepatic stellate cells ;hepatocytes;TLR4/NF-κB/NLRP3 pathway;hepatic fibrosis ;
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