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·药学研究·
胆南星对四氯化碳致小鼠急性肝损伤的保护作用及机制研究
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史丛晶 ,邓雅方 ,张志宏 ,李 彪 ,苏慧琳 ,彭东辉 ,曾元宁 ,王秋红 (1.广东药科大学中药学院/广东省中
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药饮片规范化炮制工程技术研究中心,广州 510006;2.黑龙江中医药大学药学院/教育部北药基础与应用研究
重点实验室/黑龙江中药及天然药物药效物质基础研究重点实验室,哈尔滨 150040)
中图分类号 R965 文献标志码 A 文章编号 1001-0408(2022)23-2835-05
DOI 10.6039/j.issn.1001-0408.2022.23.04
摘 要 目的 研究胆南星对四氯化碳(CCl4 )致小鼠急性肝损伤的保护作用及可能的作用机制。方法 将50只小鼠按体质量随机
分为正常组、模型组、阳性对照组(联苯双酯滴丸,150 mg/kg)和胆南星低、高剂量组(0.78、2.34 g/kg),每组10只。每天灌胃给药1
次,连续7 d。末次灌胃2 h后,除正常组外的其余各组小鼠均腹腔注射0.2% CCl4-橄榄油溶液复制急性肝损伤模型。腹腔注射17 h
后,按照试剂盒方法检测小鼠血清中丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)
和肝组织中丙二醛(MDA)、超氧化物歧化酶(SOD)水平,测定小鼠的肝脏指数,采用苏木精-伊红染色法观察小鼠肝组织的病理
形态学变化并对肝损伤程度进行量化评分,采用实时荧光定量PCR法检测小鼠肝组织中IL-6、TNF-α mRNA表达水平,采用Western
blot法检测小鼠肝组织中酪氨酸激酶2(JAK2)、信号传导及转录激活因子3(STAT3)、核因子κB p65(NF-κB p65)蛋白表达水平。
结果 与正常组比较,模型组小鼠 ALT、AST、IL-6、TNF-α、MDA 水平和肝脏指数显著升高(P<0.05),SOD 水平显著降低(P<
0.05);IL-6、TNF-α mRNA及JAK2、STAT3、NF-κB p65蛋白表达显著上调(P<0.05);肝索结构严重紊乱,肝细胞有较多炎症细胞
浸润,肝损伤程度评分显著升高(P<0.05)。与模型组比较,胆南星低、高剂量组小鼠肝组织病理变化及上述指标水平均显著改善
(P<0.05)。结论 胆南星对CCl4致小鼠急性肝损伤具有保护作用,其机制可能与抑制JAK2/STAT3/NF-κB信号通路介导的炎症
反应及抗氧化应激作用有关。
关键词 胆南星;急性肝损伤;炎症反应;氧化应激;核因子κB p65;信号传导及转录激活蛋白3;酪氨酸激酶2
Study on protective effect and mechanism of Arisaema Cum Bile on acute liver injury induced by CCl4 in
mice
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SHI Congjing ,DENG Yafang ,ZHANG Zhihong ,LI Biao ,SU Huilin ,PENG Donghui ,ZENG Yuanning ,
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WANG Qiuhong(1. College of Chinese Medicine, Guangdong Pharmaceutical University/Technical Research
Center for Standardized Processing of Chinese Herbal Medicine Decoction Pieces, Guangzhou 510006, China;2.
School of Pharmacy, Heilongjiang University of Chinese Medicine/Key Laboratory of Basic and Applied
Research of Northern Medicine of Ministry of Education/Heilongjiang Key Laboratory of Pharmacodynamic
Material Bases Research of Traditional Chinese Medicine and Natural Medicine, Harbin 150040, China)
ABSTRACT OBJECTIVE To investigate the protective effect and potential mechanism of Arisaema Cum Bile on acute liver
injury induced by carbon tetrachloride (CCl4 ) in mice. METHODS Fifty mice were randomly divided into normal group, model
group, positive control group (Biphenyl diester dropping pills, 150 mg/kg), Arisaema Cum Bile low-dose and high-dose groups
(0.78, 2.34 g/kg), with 10 mice in each group. The mice in each group were given relevant medicine intragastrically, once a day,
for 7 consecutive days. Two hours after the last administration, those groups were given intraperitoneal injection of 0.2% CCl4-olive
oil solution to induce acute liver injury model except for normal group. Seventeen hours after intraperitoneal injection, the serum
levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), interleukin-6 (IL-6), tumor necrosis factor-α(TNF-
α), and malondialdehyde (MDA), superoxide dismutase (SOD) in liver tissue were measured with kit method. The hepatic index
was detected. The pathological changes of liver tissue were observed by HE staining, and the degree of liver injury was scored
quantitatively. The mRNA expressions of TNF-α and IL-6 in liver tissue were detected by real-time fluorescence quantitative PCR;
the protein expressions of Janus kinase 2 (JAK2), signal transducer and activator of transcription protein 3 (STAT3) and nuclear
factor-κB p65 (NF-κB p65) in liver tissue were detected by
Δ 基金项目 国家重点研发计划项目(No.2018YFC1707100);广东
Western blot assay. RESULTS Compared with normal group,
省重点领域研发计划(No.2022B1111120002)
the levels of ALT, AST, IL-6, TNF-α and MDA, the hepatic
*第一作者 硕士研究生。研究方向:中药炮制原理。E-mail:
15194178895@163.com index were increased significantly (P<0.05), while the level
# 通信作者 教授,博士生导师,博士。研究方向:中药炮制原理。 of SOD was decreased significantly (P<0.05); the mRNA
E-mail:qhwang668@sina.com expressions of IL-6 and TNF-α, and the protein expressions of
中国药房 2022年第33卷第23期 China Pharmacy 2022 Vol. 33 No. 23 · 2835 ·