4-羟基苯并噁唑-2-酮对四氯化碳诱导大鼠肝纤维化的改善作用及机制研究-中国药房

4-羟基苯并噁唑-2-酮对四氯化碳诱导大鼠肝纤维化的改善作用及机制研究

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篇名：	4-羟基苯并噁唑-2-酮对四氯化碳诱导大鼠肝纤维化的改善作用及机制研究
TITLE：
摘要：	目的：观察4-羟基苯并噁唑-2-酮（HBOA）对四氯化碳（CCl4）诱导大鼠肝纤维化的改善作用及其机制。方法：将雄性SD大鼠随机分为正常对照组、模型组、秋水仙碱组（阳性对照，0.4 mg/kg）和HBOA低、中、高剂量组（50、75、100 mg/kg），每组12只。除正常对照组大鼠灌胃等体积生理盐水外，其余各组大鼠均灌胃50％CCl4-橄榄油溶液（2 mL/kg，首剂量加倍），每周2次，连续12周，复制肝纤维化模型。自造模第9周起，各给药组大鼠均灌胃相应药物，正常对照组和模型组大鼠均灌胃等体积0.6％羧甲基纤维素钠溶液，每天1次，连续4周。末次给药后，检测各组大鼠血清中丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、白细胞介素1β（IL-1β）、IL-10的含量以及肝组织中核因子κB p65（NF-κB p65）、肿瘤坏死因子α（TNF-α）、IL-6、细胞间黏附因子1（ICAM-1）蛋白的表达水平。结果：与正常对照组比较，模型组大鼠肝组织中NF-κB p65阳性表达明显增多，且其血清ALT、AST、IL-1β含量以及肝组织中NF-κB p65、TNF-α、IL-6、ICAM-1蛋白表达水平均显著升高，血清IL-10含量显著降低（P＜0.05）。与模型组比较，各给药组大鼠肝组织中NF-κB p65阳性表达均有不同程度的减弱，且其血清ALT、AST、IL-1β含量以及肝组织中NF-κB p65、TNF-α、IL-6、ICAM-1蛋白表达水平均显著降低，血清IL-10含量均显著升高（P＜0.05）。结论：HBOA对CCl4致大鼠肝纤维化具有一定的改善作用，其作用机制可能与其阻断NF-κB信号通路继而减轻炎症反应以及下调ICAM-1蛋白的表达有关。
ABSTRACT：	OBJECTIVE： To observe the improvement effect and mechanism of 4-hydroxy-2-benzoxazolone （HBOA） on carbon tetrachloride-induced hepatic fibrosis in rats. METHODS： Male SD rats were randomly divided into normal control group， model group， colchicine group （positive control， 0.4 mg/kg） and HBOA low-dose， medium-dose and high-dose groups （50， 75， 100 mg/kg）， with 12 rats in each group. Except for normal control group was given constant volume of normal saline intragastrically， other groups were given 50％CCl4-olive oil solution （2 mL/kg， initial dose double） intragastrically， twice a week， for consecutive 12 weeks， to induce hepatic fibrosis model. Since the 9th week of modeling， administration groups were given relevant medicine intragastrically. Normal control group and model group were given constant volume of 0.6％ Carboxymethylcellulose sodium solution intragastrically， once a day， for consecutive 4 weeks. After last administration， the serum contents of ALT， AST， IL-1β and IL-10， the protein expression of NF-κB p65， TNF-α， IL-6 and ICAM-1 in liver tissue were determined. RESULTS： Compared with normal control group， the positive expression of NF-κB p65 in liver tissue was increased significantly in model group； serum contents of ALT， AST and IL-1β as well as protein expression of NF-κB p65， TNF-α， IL-6 and ICAM-1 in liver tissure were increased significantly， while serum content of IL-10 was decreased significantly （P＜0.05）. Compared with model group， the positive expression of NF-κB p65 in liver tissue were decreased to different extents in administration groups； serum contents of ALT， AST and IL-1β as well as protein expression of NF-κB p65， TNF-α， IL-6 and ICAM-1 in liver tissue were decreased significantly， while serum content of IL-10 was increased significantly （P＜0.05）. CONCLUSIONS： HBOA can improve carbon tetrachloride-induced hepatic fibrosis in rats， and the mechanism of which may be associated with relieving inflammatory reaction by blocking NF-κB signaling pathway and down-regulating the protein expression of ICAM-1.
期刊：	2019年第30卷第6期
作者：	黄秀昆，孙雪梅，朱勋帅，刘林，林兴，林军
AUTHORS：	HUANG Xiukun，SUN Xuemei，ZHU Xunshuai，LIU Lin，LIN Xing，LIN Jun
关键字：	4-羟基苯并噁唑-2-酮；肝纤维化；核因子κB信号通路；炎症因子；细胞间黏附因子；大鼠
KEYWORDS：	4-hydroxy-2-benzoxazolone； Hepatic fibrosis； NF-κB signaling pathway； Inflammatory factors； ICAM； Rats
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