Effects of dexamethasone, cyproheptadine, anisodamine, and dinoprostone on TNF_α production in endotoxic shock  

Effects of dexamethasone, cyproheptadine, anisodamine, and dinoprostone on TNF α production in endotoxic shock 1

作　　者：王立赞[1,2,3] 刘玉琴[1,2,3] 崔运河[1,2,3] 朱凡河 王保生[1,2,3] 论宁 

机构地区：[1]济宁医学院病理生理学教研室 [2]组织学与胚胎学教研室 [3]生物化学教研室

出　　处：《中国药理学报》1999年第2期171-174,共4页Acta Pharmacologica Sinica

摘　　要：目的：研究地塞米松（Ｄｅｘ）、噻庚啶（Ｃｙｐ）、山莨菪碱（Ａｎｉ）和地诺前列酮（Ｄｉｎ）对脂多糖（ＬＰＳ）诱导的肿瘤坏死因子（ＴＮＦα）基因表达的影响和抑制ＴＮＦα产生的抗休克作用．方法：Ｗｉｓｔａｒ大鼠静脉注射ＬＰＳ（ＥｃｏｌｉＯ１１１Ｂ４，５ｍｇ·ｋｇ－１）复制内毒素休克模型．Ｎｏｒｔｈｅｒｎ印迹杂交分析肝脏ＴＮＦαｍＲＮＡ表达，放射免疫法测定血浆ＴＮＦα的含量．结果：ＬＰＳ攻击后２ｈ肝脏ＴＮＦαｍＲＮＡ表达水平显著增高（放射性自显影扫描分析３８±１０ｖｓ盐水对照组１１±８，Ｐ＜００１）；血浆ＴＮＦα水平明显升高［（２２±３）μｇ·Ｌ－１ｖｓ盐水对照组（２２±１０）μｇ·Ｌ－１，Ｐ＜００１］．静脉注射ＬＰＳ后立即静脉注射Ｄｅｘ５，Ｃｙｐ５，Ａｎｉ１０及Ｄｉｎ２ｍｇ·ｋｇ－１均能显著降低大鼠肝脏ＴＮＦαｍＲＮＡ水平和血浆ＴＮＦα含量，提高ＬＰＳ２０ｍｇ·ｋｇ－１攻击的小鼠２４ｈ的存活率．结论：Ｄｅｘ，Ｃｙｐ，Ａｎｉ和Ｄｉｎ均能显著抑制ＬＰＳ诱导的ＴＮＦα基因表达，具有较强的抗休克作用．AIM: To study the effects of dexamethasone (Dex), cyproheptadine (Cyp), anisodamine (Ani), and dinoprostone (Din) on lipo￣poly￣sac￣charides (LPS) induced tumor necrosis factor alpha (TNF α) gene expression and antishock effects of inhibiting TNF α production. METHODS: Endotoxic shock in rats was produced by iv injection of LPS ( E coli O111B4, 5 mg·kg -1 ). TNF α mRNA accumulation was as￣sessed by Northern blot. Plasma TNF α con￣tents were determined by radioimmunoassay. RE￣SULTS: The TNF α mRNA levels in rat liver at 2 h after LPS challenge was increased obviously (autoradiograms analyzed by scanning were 38±10 vs saline control 11±8, P <0 01). The plasma TNF α contents were marked￣ly increased [(22±3) μg·L -1 vs saline control (2 2±1 0) μg·L -1 , P <0 01]. Dex 5, Cyp 5, Ani 10, or Din 2 mg·kg -1 immediately injected after iv LPS markedly decreased the TNF α mRNA levels in rat liver and plasma TNF α contents. The Dex, Cyp, Ani, and Din improved the mouse sur￣vival rate 24 h after LPS 20 mg·kg -1 chal￣lenge. CON￣CLU￣SION: Dex, Cyp, Ani, and Din strongly inhibit LPS induced TNF α gene ex￣pres￣sion, and have a beneficial antishock effects.

关 键 词：内毒素休克 TNFα 地塞米松 噻庚啶 山莨菪碱 

分 类 号：R631.4[医药卫生—外科学] R977.1[医药卫生—临床医学]