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三味甘露对大鼠肝纤维化的改善作用及机制
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          陈秀梅 ,王英杰 ,赵成周 ,李 真 ,张文惠平 ,罗唐君 ,刘 鑫 ,孙胜男 (1.青海大学医学部药学系,西宁
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          810016;2.青海大学藏医学院,西宁 810016)
          中图分类号  R965;R285.5      文献标志码  A      文章编号  1001-0408(2024)06-0707-05
          DOI  10.6039/j.issn.1001-0408.2024.06.12
          摘  要  目的  探讨藏药三味甘露对大鼠肝纤维化的改善作用及机制。方法  实验大鼠分为正常组、模型组、水飞蓟宾组(阳性对
          照,50 mg/kg)和三味甘露低、中、高剂量组(80、250、800 mg/kg),除正常组外,其余组以四氯化碳(CCl4 )腹腔注射诱导大鼠肝纤维
          化模型。造模给药第6周开始,各组大鼠分别灌胃生理盐水或相应药物。第9周实验结束,计算大鼠肝脏指数和脾脏指数;以苏木
          素-伊红、Masson及Sirus Red染色观察肝组织病理结构和纤维化程度;检测血清中丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、
          Ⅲ型前胶原(PC Ⅲ)、Ⅳ型胶原(COL-Ⅳ)、白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)、IL-1β含量与肝组织中透明质酸(HA)、
          层粘连蛋白(LN)含量。结果  与模型组相比,三味甘露各剂量组和水飞蓟宾组大鼠肝损伤和胶原纤维沉积均有不同程度改善,血
          清中ALT、AST、PC Ⅲ、COL-Ⅳ、IL-6、TNF-α、IL-1β含量以及肝组织中HA、LN含量均显著降低(P<0.05或P<0.01)。结论  三味
          甘露能够通过抑制胶原纤维生成,降低转氨酶、HA、LN、PC Ⅲ和COL-Ⅳ含量,减轻炎症反应,从而缓解CCl4诱导的大鼠肝纤维化
          进程。
          关键词  三味甘露;肝纤维化;炎症;病理改变;胶原蛋白


          Ameliorative effect and mechanism of Sanwei ganlu on hepatic fibrosis in rats
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          CHEN Xiumei ,WANG Yingjie ,ZHAO Chengzhou ,LI Zhen ,ZHANG Wenhuiping ,LUO Tangjun ,LIU Xin ,
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          SUN Shengnan (1.  Dept.  of  Pharmacy,  Faculty  of  Medicine,  Qinghai  University,  Xining  810016,  China;
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          2. College of Tibetan Medicine, Qinghai University, Xining 810016, China)
          ABSTRACT   OBJECTIVE  To  investigate  the  ameliorative  effects  and  mechanism  of  Sanwei  ganlu  on  hepatic  fibrosis  in  rats.
          METHODS  The  rats  were  randomly  divided  into  normal  group,  model  group,  silibinin  group (positive  control,  50  mg/kg),  and
          Sanwei ganlu low-dose, medium-dose, and high-dose groups (80, 250, 800 mg/kg). Except for normal group, hepatic fibrosis rat
          models  were  established  by  intraperitoneal  injection  of  CCl4  in  the  other  groups  of  rats.  Starting  from  the  6th  week  of  modeling
          administration, they were given normal saline or corresponding drugs intragastrically at the same time. At the end of the ninth-week
          experiment,  liver  and  spleen  indexes  of  rats  were  calculated;  the  pathological  structure  and  fibrosis  changes  of  liver  tissue  were
          observed  by  HE,  Masson  and  Sirus  Red  staining.  The  contents  of  alanine  transaminase (ALT),  aspartate  transaminase (AST),
          procollagen type Ⅲ (PC Ⅲ), collagen type Ⅳ (COL-Ⅳ), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and IL-1β in
          serum, and hyaluronic acid (HA) and laminin (LN) in liver tissue were all detected. RESULTS Compared with the model group,
          the liver injury and collagen fiber deposition of rats were improved to different extents in Sanwei ganlu groups and silibinin group;
          the  contents  of ALT, AST,  PC  Ⅲ,  COL-Ⅳ,  IL-6,  TNF-α  and  IL-1β  in  serum  as  well  as  the  contents  of  HA  and  LN  in  liver
          tissue  significantly  decreased (P<0.05  or  P<0.01).  CONCLUSIONS  Sanwei  ganlu  can  alleviate  the  progression  of  hepatic
          fibrosis in rats, possibly by inhibiting the synthesis of collagen fiber, reducing transaminase content, down-regulating the levels of
          HA, LN, PC Ⅲ and COL-Ⅳ, and reducing the inflammatory response.
          KEYWORDS    Sanwei ganlu; hepatic fibrosis; inflammation; pathological changes; collagen



              肝纤维化是肝脏受到慢性或反复损伤后,在炎症的                         刺激下引起的可逆性病理改变,是发展为肝硬化及肝癌
                                                             的早期阶段。肝纤维化主要由病毒性肝炎、自身免疫性
             Δ 基金项目 青海省中藏医药科研创新项目(No.J2020007);青海
          大学青年科研基金(No.2021-QYY-7);青海大学医学部中青年科技项              疾病、脂肪肝和酒精肝等引起,主要表现为细胞外基质
          目(No.2021-kyy-6)                                  (extracellular matrix,ECM)过度沉积与增生 。炎症是
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             *第一作者 硕士研究生。研究方向:中藏药药效与机制。E-                                                                  [2]
                                                             肝纤维化发展的主要因素,可大幅度加快纤维化进程 。
          mail:2062553782@qq.com
                                                             因此,减少 ECM 的沉积,抑制炎症因子的释放,是抗肝
             # 通信作者 副教授,硕士生导师,博士。研究方向:中藏药药效与
          机制。E-mail:sunsn@qhu.edu.cn                         纤维化研究的重点。

          中国药房  2024年第35卷第6期                                                 China Pharmacy  2024 Vol. 35  No. 6    · 707 ·
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