Page 25 - 《中国药房》2022年23期
P. 25

·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
                                                                                                       Δ

                                                                   1
                                  2
                                                   1
                                                                           1 #
                                          1
                                                           2
                          1
          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
                 1*
          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
                                     1
                                                                          1
                                                               1
                      1
                                                                                                           1
                                                      2
                                                                                          2
          SHI Congjing ,DENG Yafang ,ZHANG Zhihong ,LI Biao ,SU Huilin ,PENG Donghui ,ZENG Yuanning ,
                        1
          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 ·
   20   21   22   23   24   25   26   27   28   29   30