五味子广泛用于保护肝脏。药物性肝细胞损伤有多种机制,其中内质网(ER)应激诱导的细胞损伤起着重要作用。然而,关于五味子是否可以通过影响内质网应激来抑制利福平(RFP)诱导的肝细胞损伤,目前尚不清楚。在我们的研究中,首先,L02细胞用不同浓度的RFP处理不同的时间间隔,和细胞凋亡,存活率和内质网应激基因和葡萄糖调节蛋白78(GRP78)的蛋白表达,PKR样ER激酶(PERK),激活转录因子(ATF)4,C/EBP同源蛋白(CHOP),ATF6,富含精氨酸,在早期肿瘤(ARMET)中突变,测量需要β-肌醇的酶1(IRE1)和X-盒结合蛋白1(XBP-1)。我们发现RFP增加了L02细胞的凋亡,细胞存活率降低,并增加了GRP78,PERK的基因和蛋白质表达水平,ATF4,CHOP,ATF6,ARMET,p-IRE1和XBP-1,表明RFP可以诱导肝细胞损伤,损伤程度与RFP剂量和时间呈正相关。接下来,我们用五味子素B处理RFP损伤的肝细胞。我们发现五味子素B以剂量依赖和时间依赖的方式提高细胞存活率,细胞凋亡率降低,GRP78,PERK的蛋白质和基因表达水平降低,ATF4,CHOP,ATF6、ARMET和XBP-1。这些结果表明五味子素B通过抑制内质网应激减轻RFP诱导的L02细胞损伤。
Schisandra chinensis is widely used and effective in protecting liver. There are many mechanisms of drug-induced hepatocyte injury, among which endoplasmic reticulum (ER) stress-induced cell injury plays an important role. However, little is known about whether schisandra chinensis can inhibit rifampicin (RFP)-induced hepatocyte injury by affecting ER stress. In our study, firstly, L02 cells were treated with different concentrations of RFP for different time intervals, and the apoptosis, survival rate and endoplasmic reticulum stress gene and protein expressions of glucose-regulated protein 78 (GRP 78), PKR-like ER kinase (PERK), activating transcription factor (ATF)4, C/EBP-homologus protein (CHOP), ATF6, arginine-rich, mutated in early stage tumors (ARMET), p-inositol-requiring enzyme 1 (IRE1) and X-box binding protein 1 (XBP-1) were measured. We found that RFP increased apoptosis of L02 cells, decreased cell survival, and increased the gene and protein expression levels of GRP78, PERK, ATF4, CHOP, ATF6, ARMET, p-IRE1 and XBP-1, suggesting that RFP could induce hepatocyte injury, and the degree of injury was positively correlated with the dose and time of RFP. Next, we treated RFP-damaged hepatocytes with schizandrin B. We found that schizandrin B increased cell survival rate in dose-dependent and time-dependent manner, decreased cell apoptosis rate, and reduced protein and gene expression levels of GRP78, PERK, ATF4, CHOP, ATF6, ARMET and XBP-1. These results indicate that schizandrin B alleviates RFP-induced injury in L02 cells by inhibiting ER stress.