Juzentaihoto reduces post-partial hepatectomy hyperammonemia by stabilizing intestinal microbiota

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著者

    • Imazu Yoshihiro IMAZU Yoshihiro
    • 慶應義塾大学医学部漢方医学講座 Department of Kampo Medicine, Keio University, School of Medicine:Department of Surgery, Keio University, School of Medicine:Department of Surgery, Saiseikai central hospital
    • TSUIJI Kenji
    • 慶應義塾大学医学部漢方医学講座 Department of Kampo Medicine, Keio University, School of Medicine:Department of Surgery, Keio University, School of Medicine
    • TODA Takahiro
    • 慶應義塾大学医学部漢方医学講座 Department of Kampo Medicine, Keio University, School of Medicine:Department of Clinical Pharmacokinetics, Hoshi University, School of Pharmacy
    • ISHIGE Atsushi
    • 慶應義塾大学医学部漢方医学講座 Department of Kampo Medicine, Keio University, School of Medicine
    • SUGIYAMA Kiyoshi
    • Department of Clinical Pharmacokinetics, Hoshi University, School of Pharmacy
    • BENNO Yoshimi
    • Japan Collection of Microorganisms, RIKEN BioResouce Center
    • KITAJIMA Masaki
    • 慶應義塾大学医学部漢方医学講座 Department of Kampo Medicine, Keio University, School of Medicine:Department of Surgery, Keio University, School of Medicine

抄録

高アンモニア血症に対する十全大補湯の効果と腸内菌叢の安定化作用を検討した。肝硬変患者における肝細胞癌の治療として外科的治療は最も予後が期待できる。しかし,術後合併症は治療に携わるものにとって重大な問題である。中でも高アンモニア血症は肝性脳症の原因となる一方,残肝機能に影響を与え,術後の腸管運動の低下によるbacterial translocationの誘因となる。本研究ではマウスに十全大補湯を術前経口投与することで肝部分切除後の血清アンモニア値の上昇が抑制された。肝機能障害は十全大補湯では改善されなかった。十全大補湯非投与群では有意な血清アンモニア値の上昇を認めたが,投与群では上昇が抑えられた。T-RFLPによる腸内菌叢の解析結果から肝部分切除術によりそのパターンの変化が認められたが,投与群ではパターンの変化は認められなかった。非投与群に対して,非手術群と十全大補湯投与群はCluster解析において72%の類似性を認めた。以上より,十全大補湯は肝部分切除後に認められる腸内細菌叢の変動を抑え,安定化させることによって血清アンモニア値の上昇を抑制しているものと考えられた。

We examined the preventive effect of the Kampo medicine Juzentaihoto (JTX) on post-partial hepatectomyinduced hyperammonemia, a frequent and potentially fatal consequence of this surgery for resection of hepatocellular carcinomas. In most cases, these liver tumors are associated with pre-existing liver damage such as cirrhosis or chronic hepatitis. Post-surgical hyperammonemia harms further the remaining liver as well brain and other vital functions. With pre-surgical JTX administration, this post-surgical hyperammonemia is suppressed significantly. To explain this phenomenon, we first hypothesized that JTX prevents further damage of the liver, a site of ammonia metabolism. However, post-surgical liver dysfunction is not improved with JTX. Thus we focused on the other source of ammonia, the intestinal microbiota, as the source of the hyperammonemia. To examine the possible effect of JTX on intestinal microbiota, terminal restriction fragment polymorphism (T-RFLP), a culture-independent microbial analysis, was used to document change in the intestinal microbiota with JTX. We documented that partial hepatectomy changed the intestinal microbiota. Then we demonstrated that with oral JTX administration, this post-surgical change of the intestinal microbiota was not observed even after partial hepatectomy. We also showed that the representative ammoniaproducing bacteria, Bacteroides, increased with partial hepatectomy and decreased with JTX administration. Cluster analysis of fecal microbiota suggests that JTX administration stabilized the intestinal microbiota and maintained the pre-surgical microbial analysis environment of the gut. This study suggests that JTX is useful to prevent the clinically significant increases in the serum ammonia levels after partial hepatectomy.

収録刊行物

  • 和漢医薬学雑誌

    和漢医薬学雑誌 23(6), 208-215, 2006-12-20

    和漢医薬学会

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各種コード

  • NII論文ID(NAID)
    110006152053
  • NII書誌ID(NCID)
    AA12035198
  • 本文言語コード
    ENG
  • 資料種別
    ART
  • ISSN
    18801447
  • NDL 記事登録ID
    8643311
  • NDL 雑誌分類
    ZS51(科学技術--薬学)
  • NDL 請求記号
    Z19-1563
  • データ提供元
    CJP書誌  NDL  NII-ELS 
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