- 作者：Satoshi Hagiwara M.D. ; Ph.D.&lowast ; ; ; saku@med.oita-u.ac.jp ; Hideo Iwasaka M.D. ; Ph.D.&lowast ; ; Chihiro Shingu M.D.&lowast ; ; Shigekiyo Matsumoto M.D.&lowast ; ; Tomohisa Uchida M.D. ; Ph.D.&dagger ; ; Taichi Nishida M.D.&lowast ; ; Shouichi Mizunaga&Dagger ; ; Tetsunori Saikawa M.D. ; Ph.D.&Dagger ; ; Takayuki Noguchi M.D. ; Ph.D.&lowast ;
- 关键词：inflammation ; cytokine ; nitric oxide ; anticoagulant ; heat stress
- 刊名：Journal of Surgical Research
- 出版年：2011
- 出版时间：December 2011
- 年：2011
- 卷：171
- 期：2
- 页码：762-768
- 全文大小：768 K
Background
Heat stroke is a condition characterized by high body temperature that can lead to hemorrhage and necrosis in multiple organs. Anticoagulants, such as danaparoid sodium (DA), inhibit various types of inflammation; however, the anti-inflammatory mechanism of action is not well understood. Given that heat stroke is a severe inflammatory response disease, we hypothesized that DA could inhibit inflammation from heat stress and prevent acute heat stroke.Materials and Methods
Male Wistar rats were given a bolus injection of saline or DA (50 U/kg body weight) into the tail vein just prior to heat stress (42 ¡ãC for 30?min). Markers of inflammation were then determined in serum and tissue samples.
Results
In rats pretreated with DA, induction of cytokines (interleukin [IL]-1¦Â, IL-6, and tumor necrosis factor [TNF]-¦Á), nitric oxide (NO), and high mobility group box 1 (HMGB1) protein were reduced compared with saline-treated rats. Histologic changes observed in lung, liver, and small intestine tissue samples of saline-treated rats were attenuated in DA-treated rats. Moreover, DA pretreatment improved survival in our rat model of heat stress-induced acute inflammation.
Conclusion
Collectively, our findings demonstrate that DA pretreatment may have value as a new therapeutic tool for heat stroke.