Immunization against Intestinal Bacterial Endotoxin Prevents Alcoholic Fatty Liver in Rats
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概要
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Accumulating evidences indicate that an endotoxin originating from intestinal gram-negative bacteria may be involved in alcohol-induced liver injury including fatty liver. Therefore, whether immunization against intestinal bacterial endotoxin blocked fatty liver induced by chronic alcohol and diet including much-unsaturated fatty acid was investigated in rats. The titer of antibody against the endotoxin increased significantly after 13 weeks of continuous immunization. Daily alcohol treatment was initiated at 12 weeks and continued for 4 weeks. Plasma glutamic pyruvic transaminase(GPT)glutamic oxaloacetic transaminase(GOT)and triglyceride(TG)levels increased significantly in non-immunized rats receiving alcohol, but not in immunized rats. Continuous alcohol treatment gradually decreased the survival rate to 60% from 13 days after beginning administration in non-immunized, but not immunized, rats. A histochemical study revealed that continuous treatment with alcohol and unsaturated fatty acids caused fatty liver in non-immunized, but not immunized, rats. This study strongly supports the hypothesis that alcohol-induced fatty liver is due to a circulating endotoxin, and suggests that immunization for endotoxin prevent the alcoholic fatty liver.腸管内細菌由来のエンドトキシンがアルコール性肝障害に関与していると言う報告が相次いでいる.この仮説を直接的に説明するため, ラットの腸管内細菌由来エンドトキシンを非動化したものを抗原に, ラットを能動免疫し, 慢性的アルコールと不飽和脂肪酸の給餌による脂肪肝誘発を阻止できるか否かを検討した.エンドトキシンに対する抗体価は投与13週から有意に増加したので, 12週目から4週間アルコールと不飽和脂肪酸の持続給餌を行った.血中GOT, GPTおよびトリグリセリド(TG)レベルは非免疫群で有意に増加したが, 免疫群では上昇しなかった.また, 非免疫群では60%のラットが死亡したのに対し, 免疫群では死亡例は見られなかった.組織検査の結果, 非免疫群にはアルコール性の脂肪肝(脂肪滴の貯留)が認められたのに対し免疫群は正常であった.以上の結果はアルコール誘発性脂肪肝は血中エンドトキシンが起因している仮説を強く支持するものである.また, エンドトキシンによる能動免疫はアルコール性脂肪肝の誘発を阻止することが示唆された.
- Japanese Society of Veterinary Scienceの論文
著者
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Misawa Naoaki
Department Of Veterinary Public Health Faculty Of Agriculture Miyazaki University
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Kuroda Haruto
Department Of Veterinary Physiology And Faculty Of Agriculture Miyazaki University
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Uchida Kazuyuki
Department Of Veterinary Pathology Graduated School Of Agricultural And Life Sciences The University
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Murakami Noboru
Department Of Dermatology St. Marianna University School Of Medicine
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NAKAHARA Keiko
Department of Animal Physiology, Faculty of Agriculture, University of Miyazaki
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Nishimura Gendo
Department of Veterinary Physiology, Faculty of Agriculture, University of Miyazaki
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Muranaka Miki
Department of Veterinary Pathology, Faculty of Agriculture, University of Miyazaki
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MURAKAMI Noboru
Department of Animal Physiology, Faculty of Agriculture, University of Miyazaki
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