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化瘀消肿汤对深静脉血栓形成大鼠炎症反应的影响
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          麦 叶 ,林道斌,刘海林,林瑶瑶,许青青,顾 勇(海南省中医院重症医学科,海口 570203)
                *
                                                       #
          中图分类号  R965;R543.6      文献标志码  A      文章编号  1001-0408(2023)14-1697-06
          DOI  10.6039/j.issn.1001-0408.2023.14.07


          摘  要  目的  探讨化瘀消肿汤(HXD)对深静脉血栓形成(DVT)大鼠炎症反应的影响。方法  将雄性 SD 大鼠分为对照组(CK
          组)、模型组(Model组)、HXD低剂量组(HXD-L组,HXD 10.86 mg/kg)、HXD中剂量组(HXD-M组,HXD 21.71 mg/kg)、HXD高剂
          量组(HXD-H组,HXD 32.57 mg/kg)、阳性对照组(LMWHS组,低分子量肝素钠600 IU/kg)、沉默信息调节因子2(SIRT2)抑制剂组
         (AK-7组,AK-7 20 mg/kg)、HXD-M联合AK-7组(HXD-M+AK-7组,HXD 21.71 mg/kg+AK-7 20 mg/kg),每组12只。除CK组外,
          其余组大鼠均采用Reyers法构建DVT大鼠模型;建模后,各药物组分别灌胃/腹腔注射相应药液,每天1次,持续2周。末次给药
          24 h后,检测大鼠凝血功能指标[活化部分凝血活酶时间(APTT)、凝血酶时间(TT)、凝血酶原时间(PT)、纤维蛋白原(FIB)]和血
          清、下腔静脉组织中炎症指标[白细胞介素1β(IL-1β)、IL-6、肿瘤坏死因子α(TNF-α)],观察其血栓形成情况并称定血栓湿重、干
          重,检测下腔静脉组织中组织因子(TF)、SIRT2蛋白的表达情况和核因子κB(NF-κB)p65的磷酸化、乙酰化水平。结果  与CK组
          比较,Model组大鼠的APTT、TT、PT均显著缩短(P<0.05);FIB含量,IL-1β、IL-6、TNF-α水平,静脉血栓湿重、干重,TF蛋白染色
          评分,NF-κB p65 蛋白的磷酸化、乙酰化水平均显著升高(P<0.05);下腔静脉血管内充满血栓,SIRT2 蛋白的表达水平显著降低
         (P<0.05)。与Model组比较,HXD-L组、HXD-M组、HXD-H组和LMWHS组大鼠上述指标均显著改善,且HXD-M组、HXD-H和
          LMWHS组的效果显著优于HXD-L组(P<0.05);AK-7组大鼠上述指标的变化趋势与之相反,且AK-7可减弱中剂量HXD对模型
          大鼠炎症反应的抑制作用(P<0.05)。结论  HXD可能通过激活SIRT2/NF-κB信号通路来抑制DVT大鼠的炎症反应。
          关键词  化瘀消肿汤;深静脉血栓形成;炎症反应;沉默信息调节因子2/核因子κB信号通路

          Influence of Huayu xiaozhong decoction on inflammatory response in rats with deep vein thrombosis
          MAI Ye,LIN Daobin,LIU Hailin,LIN Yaoyao,XU Qingqing,GU Yong(Intensive Care Unit, Hainan Traditional
          Chinese Medicine Hospital, Haikou 570203, China)


          ABSTRACT   OBJECTIVE  To  investigate  the  influence  of  Huayu  xiaozhong  decoction (HXD)  on  inflammatory  response  in  rats
          with  deep  vein  thrombosis (DVT).  METHODS  The  male  SD  rats  were  divided  into  control  group (CK  group),  model  group
         (Model  group),  HXD  low-dose  group (HXD-L  group,  HXD  10.86  mg/kg),  HXD  medium-dose  group (HXD-M  group,  HXD
          21.71  mg/kg),  HXD  high-dose  group (HXD-H  group,  HXD  32.57  mg/kg),  positive  control  group (LMWHS  group,  low
          molecular  weight  heparin  sodium  600  IU/kg),  silent  information  regulator  2 (SIRT2)  inhibitor  group (AK-7  group, AK-7  20
          mg/kg),  HXD-M+AK-7  group (HXD  21.71  mg/kg+AK-7  20  mg/kg),  with  12  rats  in  each  group.  Except  for  the  CK  group,  the
          DVT  rat  was  induced  by  the  Reyers  method  in  other  groups;  after  modeling,  administration  groups  were  given  relevant  medicine
          intragastrically/intraperitoneally, once a day, for consecutive 2 weeks. Twenty-four hours after the last medication, the coagulation
          function indexes [activated partial thromboplastin time (APTT), thrombin time (TT), prothrombin time (PT), fibrinogen (FIB)]
          and inflammatory indexes in serum and inferior vena cava tissue [interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α)]
          of  rats  were  detected.  The  formation  of  thrombus  was  observed,  and  the  wet  and  dry  masses  of  the  thrombus  were  weighed.  The
          protein expressions of tissue factor (TF) and SIRT2 as well as the phosphorylation and acetylation levels of nuclear factor kappa B
         (NF-κB) p65 in inferior vena cava tissue were detected. RESULTS Compared with CK group, APTT, TT and PT of rats in Model
          group  were  shortened  significantly(P<0.05);  the  content  of  FIB,  the  levels  of  IL-1β,  IL-6  and  TNF- α,  wet  weight  and  dry
          weight  of  venous  thrombus, TF  protein  staining  score,  the  phosphorylation  and  acetylation  levels  of  NF-κB  p65  protein  increased
          significantly (P<0.05);  the  inferior  vena  cava  was  full  of  thrombus,  and  the  protein  expression  of  SIRT2  decreased (P<0.05).
          Compared with Model group, above indexes of HXD-L group, HXD-M group, HXD-H group and LMWHS group were improved,
          while the improvement effects of HXD-M group, HXD-H group and LMWHS group were significantly better than those of HXD-L
                                                             group (P<0.05). The trends of the corresponding indicators in
             Δ  基金项目 海 南 省 自 然 科 学 基 金 高 层 次 人 才 项 目(No.
                                                             AK-7  group  were  opposite  to  the  above (P<0.05);  AK-7
          820RC773);海南省卫生计生行业科研项目(No.20A200342)              attenuated  the  inhibitory  effect  of  medium-dose  HXD  on  the
             *第一作者 副主任医师,硕士。研究方向:急危重症医学。E-
                                                             inflammatory   response   in   model   rats   (P<0.05).
          mail:maiye136@163.com
             # 通信作者 副主任医师,博士。研究方向:脑缺血损伤与保护。                  CONCLUSIONS  HXD  may  inhibit  the  inflammatory  response
          E-mail:18089866688@163.com                         of DVT rats by activating SIRT2/NF-κB signaling pathway.


          中国药房  2023年第34卷第14期                                              China Pharmacy  2023 Vol. 34  No. 14    · 1697 ·
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