| 肝阻血再灌流障害に対する内因性及び外因性ラジカルスカベンジャーの効果. Effects of Endogenous and Exogenous Radical Scavengers in Liver Ischemia-Reperfusion Injury : β1-3glucan Induced SOD and New Radical Scavenger, ADF | |||||||||||||
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Abstract | |||||||||||||
| 肝臓外科, 肝移植後の際, 問題となる肝阻血再潅流障害に活性酸素が関与していることが明らかになり, 障害防御に各種radical seavengerの外的投与が試みられている。しかし, 元来肝臓にはradical scavengerが抱負に存在する。そこで, 内なる防御として内因性radical scavengerの誘導を試みた。また外からの防御として, 新しいradical scavengerであるADFの外的投与を行い, 内因性, 外因性また肝実質細胞, 非実質細胞の両面から阻血再潅流障害の軽減を試みた。実験には8週齢雄性Wistar系ラットを用いた。実験I(SODの誘導):β1-3glucan投与後経日的に肝臓SOD活性を測定した。実験II(阻血再潅流実験):60分阻血再潅流モデルを用い以下の群で実験を行った。A群:ADF100μgを阻血前・後に経静脈投与。B群:β1-3glucan 1mg投与, C群:β1-3glucan 1mg隔日4回投与。D群:β1-3glucan 1mgとADF併用群。E群:対照群。検討項目:血流再開後60分時の(a)肝組織血流量, (b)肝組織MDA量。(c)7日生存率。実験III(活性酸素産生能への影響):NBT潅流法を用い, 阻血再潅流, β1-3glucan投与, ADF投与の影響を非阻血肝と比較した。実験I:β1-3glucan投与により肝組織SOD活性が上昇することを確認した。肝実質細胞, 非実質細胞の何れにおいてもSODの上昇が認められた。実験II:A, B, C, D各群でE群に比較し, (a)血流再開後60分時の肝組織血流量を高く保持し, (b)肝組織MDA量を低く抑え, (c)7日生存率が改善した。実験III:阻血再潅流により活性酸素産生能の亢進を認めたが, β1-3glucan投与, ADF投与により類洞に発生した活性酸素を消去した。またβ1-3glucan投与は活性酸素変生能に影響を及ぼさなかった。内因性のradical scavengerを誘導するという新しい方法, また新しいradical scavenger ADFの外的投与により阻血再潅流障害を軽. Free radicals are thought to be a major cause of ischemia-reperfusion injury, which sometimes results in liver failure or primary graft non-function. Many kinds of free radical scavengers have therefore been examined in order to prevent ischemia-reperfusion injury. However, a certain amount of free radical scavengers exists naturally in the liver, such as glutathione and SOD. In this study, we attempted to induce endogenous SOD as a radical scavenger. As an exogenous radical scavenger, a newly-discovered and noteworthy ADF was selected. Outbred male Wistar rats weighing 180-220 g were used in these experiments. Experiment I: Liver tissue SOD activity was examined after administration of β1-3glucan. Experiment II: Using rat ischemia-reperfusion model, liver tissue blood flow and liver tissue MDA level at 60 min after reperfusion, and 7-day survival rate were studied in each of five groups. Group A was administered 100 μg of ADF intravenously before ischemia and after reperfusion. In group B, based on the results of expeiment I, the rats were used on the 3rd day after administration of 1 mg β1-3glucan. In group C, rats were used on the 13th day after administraion of 1 mg β1-3glucan 4 times (total 4mg). Group D was administered a combination of 1 mg β1-3glucan and ADF. Group E was control. Experiment II: The ability of free radical production of Kupffer cells was evaluated using in situ NET liver perfusion method. Experiment I: Liver tissue SOD activity was elevated both in PC and NPC. Experiment II: TBF of group A and C was significantly higher than that of group E (P | |||||||||||||
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