地塞米松、噻庚啶和山莨菪碱对LPS诱导大鼠肝脏TNFα表达的影响

EFFECTS OF DEXAMETHASONE, CYPROHEPTADINE, AND ANISODAMINE ON LPS INDUCED TNFα EXPRESSION IN RAT LIVER

地塞米松（Ｄｅｘ）、噻庚啶（Ｃｙｐ） 和山莨菪碱（Ａｎｉ） 对脂多糖（ＬＰＳ） 诱导的大鼠肝脏ＴＮＦα表达的影响。Ｗｉｓｔａｒ大鼠４０ 只， 静脉注射ＬＰＳ（ＥｃｏｌｉＯ１１１Ｂ４ ５ｍ ｇ／ｋｇ） 后， 立即静脉给予Ｄｅｘ ５ｍ ｇ／ｋｇ、Ｃｙｐ５ｍ ｇ／ｋｇ 或Ａｍ ｉ１０ｍ ｇ／ｋｇ，于ＬＰＳ攻击后２ｈ 取动物的肝脏，ＡＰＡＡＰ法进行ＴＮＦα免疫组织化学研究，Ｎｏｒｔｈ－ｅｒｎ 杂交分析ＴＮＦαｍ ＲＮＡ 表达水平。结果发现ＬＰＳ攻击后２ｈ， 肝脏ＴＮＦαｍ ＲＮＡ 表达水平显著增高， 肝脏枯否氏细胞胞浆内有大量的ＴＮＦα红染颗粒。Ｄｅｘ、Ｃｙｐ 或Ａｎｉ均能显著降低大鼠肝脏ＴＮＦαｍ ＲＮＡ 水平和ＴＮＦα含量。结果表明Ｄｅｘ、Ｃｙｐ 和Ａｎｉ均显著抑制ＬＰＳ诱导的ＴＮＦα基因表达， 可能有抗感染性休克作用。

The effects of dexamethasone (Dex), cyproheptadine (Cyp), and anisodamine (Ani) on LPS induced TNFα expression in rat liver was studied. LPS (E coli O 111 B 4, 5 mg/kg) was injected intravenously to Wistar rats, and was immediately followed by iv injection of Dex 5 mg/kg, Cyp 5 mg/kg or Ani 10 mg/kg. The livers were taken at 2h after LPS challenga. TNFα mRNA levels were assessed by Northern blot. TNFα production in rat liver was studied by immunohistochemistry. The results showed that TNFα mRNA level in rat liver was increased obviously and there were a lot of immunoreactive material in Kupffer′s cells 2h after LPS challenge. Dex, Cyp and Ani markedly decreased TNFα mRNA level and TNFα immunoreactive material in rat liver. It suggests that Dex, Cyp, and Ani strongly inhibit LPS induced TNFα expression and may protect against septic shock.\;