Zhang Jiaqi, Sheng Yuchen, Shi Liang, Zheng Zhiyong, Chen Minwei, Lu Bin, Ji Lili
Shanghai Key Laboratory of Complex Prescription, The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Rd, Shanghai 201203, China.
Center for Drug Safety Evaluation and Research, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Rd, Shanghai 201203, China.
Eur J Pharmacol. 2017 Jan 15;795:160-168. doi: 10.1016/j.ejphar.2016.12.015. Epub 2016 Dec 13.
Hepatic sinusoidal obstruction syndrome (SOS) is a rare liver disease with considerable mortality. This study is designed to observe the protection of quercetin and baicalein against monocrotaline (MCT)-induced SOS in rats and its engaged mechanism. Rats were pre-administrated with MCT (90mg/kg) to induce SOS, and 6, 30h later were orally given with quercetin and baicalein (40mg/kg) twice. Results of detecting rats with liver ascites, measuring serum transaminases, total bilirubin (TBil) and bile acids (TBA), analyzing blood cells, liver histological evaluation and scanning electron microscope observation all demonstrated the detoxification of quercetin and baicalein against MCT-induced SOS in rats. Quercetin and baicalein reduced the increased metalloproteinase-9 (MMP-9) expression, liver myeloperoxidase (MPO) activity, toll-like receptor (TLR)-2,3,6,9 expression and nuclear factor κB (NFκB) transcriptional activation induced by MCT. Quercetin and baicalein reduced MCT-induced nuclear translocation of early growth response1 (Egr1) and increased expression of Serpine1 and tissue factor (TF). Quercetin and baicalein reduced MCT-induced increased liver malondialdehyde (MDA) amount and enhanced the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2). Quercetin and baicalein also abrogated MCT-induced activation of mitogen-activated protein kinases (MAPKs) and phosphatidylinositol 3-kinase (PI3K) signaling cascades. In conclusion, this study demonstrated the protection of quercetin and baicalein against MCT-induced SOS in rats, indicating the potential application of them for the treatment of SOS in clinic. Transcriptional factor NFκB, Egr1 and Nrf2-regulated inflammation, coagulation-fibrinolysis and antioxidant, and PI3K and MAPKs signaling cascades are all involved such protection.
肝窦阻塞综合征（SOS）是一种死亡率颇高的罕见肝脏疾病。本研究旨在观察槲皮素和黄芩苷对大鼠由野百合碱（MCT）诱导的SOS的保护作用及其作用机制。给大鼠预先给予MCT（90mg/kg）以诱导SOS，在6、30小时后分别口服给予槲皮素和黄芩苷（40mg/kg），每日两次。检测大鼠肝腹水、测定血清转氨酶、总胆红素（TBil）和胆汁酸（TBA）、分析血细胞、进行肝脏组织学评估以及扫描电子显微镜观察的结果均表明，槲皮素和黄芩苷对大鼠MCT诱导的SOS具有解毒作用。槲皮素和黄芩苷降低了MCT诱导的金属蛋白酶-9（MMP-9）表达增加、肝脏髓过氧化物酶（MPO）活性、Toll样受体（TLR）-2、3、6、9表达以及核因子κB（NFκB）转录激活。槲皮素和黄芩苷降低了MCT诱导的早期生长反应1（Egr1）核转位，并增加了丝氨酸蛋白酶抑制剂1（Serpine1）和组织因子（TF）的表达。槲皮素和黄芩苷降低了MCT诱导的肝脏丙二醛（MDA）量增加，并增强了核因子红细胞2相关因子2（Nrf2）的核转位。槲皮素和黄芩苷还消除了MCT诱导的丝裂原活化蛋白激酶（MAPKs）和磷脂酰肌醇3激酶（PI3K）信号级联的激活。总之，本研究证明了槲皮素和黄芩苷对大鼠MCT诱导的SOS具有保护作用，表明它们在临床上治疗SOS具有潜在应用价值。转录因子NFκB、Egr1和Nrf2调节的炎症、凝血-纤溶和抗氧化作用，以及PI3K和MAPKs信号级联均参与了这种保护作用。
