Hebei University of Chinese Medicine, Shijiazhuang 050200, China.
Hebei Higher Education Institute Applied Technology Research Center on TCM Formula Preparation, Shijiazhuang 050091, China.
J Tradit Chin Med. 2020 Dec;40(6):965-973. doi: 10.19852/j.cnki.jtcm.2020.06.008.
To observe the intervention of Chushizi (Fructus Broussonetiae) (CSZ) on drug-induced liver injury (DILI) in rats, as well as indicators of liver function, serum levels of inflammatory cytokines, and expression of proteins and mRNA associated with toll-like receptor 3 (TLR3) and the signal transducer and activator of transcription 3 (STAT3) pathway in the liver [TLR3, janus protein tyrosine kinase 2 (JAK2), c-jun, c-fos, c-Jun N-terminal kinase 2 (JNK2), and STAT3].
Forty specified pathogen free grade Sprague-Dawley rats were randomly divided into the control group, the model group, the silybin group and the CSZ group. Rats were given acetaminophen (APAP) to trigger DILI. Histopathology of the liver was observed by hematoxylin-eosin staining. The levels of alanine aminotransferase (ALT), aspartate transaminase (AST), direct bilirubin (DBIL), and total bilirubin (TBIL) in serum were detected by a semi-automatic biochemical instrument. Content of tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-13, and IL-22 in serum were detected by the enzyme-linked immunosorbent assay, the expression of TLR3, phosphorylation of JAK2 (p-JAK2), while c-jun and c-fos proteins in the liver were determined by immunohistochemistry; expression of JNK2, and STAT3 in the liver were assayed by Western blot and real-time quantitative polymerase chain reaction. P-JNK2 and p-STAT3 in the liver were assayed by Western blot.
After treatment, the activity of ALT, AST, and concentrations of TBIL, DBIL, TNF-α, IL-6, as well as IL-13 in serum, were lower than those in the model group, and expression of p-JAK2, TLR3, c-jun, c-fos, p-STAT3, and p-JNK2 could be downregulated.
Our findings suggest that CSZ is a valid medicine to alleviate APAP-induced DILI, while its partial mechanism may regulate the TLR3/JNK/ c-jun/c-fos/JAK/STAT3 pathway.
观察楮实子（CSZ）对大鼠药物性肝损伤（DILI）的干预作用，以及肝功能相关指标、血清炎症细胞因子水平、肝脏 Toll 样受体 3（TLR3）和信号转导及转录激活因子 3（STAT3）通路相关蛋白及 mRNA 的表达[TLR3、Janus 蛋白酪氨酸激酶 2（JAK2）、c-jun、c-fos、c-Jun N-末端激酶 2（JNK2）和 STAT3]。
将 40 只特定病原体级 Sprague-Dawley 大鼠随机分为对照组、模型组、水飞蓟宾组和 CSZ 组。大鼠给予对乙酰氨基酚（APAP）诱导 DILI。苏木精-伊红染色观察肝组织病理学变化。半自动生化仪检测血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、直接胆红素（DBIL）和总胆红素（TBIL）水平。酶联免疫吸附试验检测血清肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-6、IL-13 和 IL-22 含量，免疫组化法检测 TLR3、JAK2 磷酸化（p-JAK2）及肝 c-jun 和 c-fos 蛋白表达，Western blot 和实时定量聚合酶链反应检测 JNK2 和 STAT3 肝表达。Western blot 检测肝 p-JNK2 和 p-STAT3。
治疗后，ALT、AST 活性及 TBIL、DBIL、TNF-α、IL-6、IL-13 浓度均低于模型组，p-JAK2、TLR3、c-jun、c-fos、p-STAT3、p-JNK2 表达下调。
CSZ 可有效缓解 APAP 诱导的 DILI，其部分机制可能与调节 TLR3/JNK/c-jun/c-fos/JAK/STAT3 通路有关。
