The induction of heme oxygenese-1 in intestinal mucosa of septic rat

脓毒症大鼠肠黏膜血红素氧合酶1的诱导

• 批准号: 09671234
• 负责人: SHIMIZU Shuji
• 金额: $ 1.41万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671234/
• 关键词: sepsis; bilirubin; oxidative stress; intestine; heme oxygenase

Backgrounds : Bilirubin is known to be a physiological antioxidant. Heme oxygenase (HO)-1, the rate-limiting enzyme in the heme degradation, is known to be induced by oxidative stress in the liver, kidney, or brain, but its induction has not yet been known in the intestine, We studied the expression of HO-1 in intestinal mucosa induced by oxidative stress using a rat septic model. Methods : Male Wistar rats were given with lipopolysaccharide (LPS) from E.coli (10mg/kg/body weight) by peritoneal injection. They were killed at 0, 1, 3, 5, 7.5, 10 and 24 hrs and their small intestinal mucosa was harvested. In intestinal mucosa, reduced glutathione (GSH), lipid peroxide, HO-1 mRNA, HO-1 protein, bilirubin, and bilirubin oxidative metabolites (BOM) were measured. Results : Intestinal GSH level was significantly decreased after 3 to 5 hrs by 40% of the control level. Lipid peroxides level was 1 .7-folds of control level at 5 hrs. The level of HO-1 mRNA increased to 3 times of the control at 3 hrs and HO-1 protein was strongly detected 7.5 hrs after LPS injection. Bilirubin level increased to 4-folds of control (peak level) at 10 hrs and BOM showed 5-folds increase with the peak level at 10 hrs. Conclusions : Sepsis reduced the GSH content and increased lipid peroxides. This intestinal oxidative stress induced the expression of HO-1 mRNA as well as the production of the protein in the intestinal mucosa. Bilirubin production and subsequent oxidation to BOM indicates that bilirubin acted as an antioxidant. This suggested that small intestine had ability to respond quickly to oxidative stress in sepsis, not just as a digestive and absorptive organ.

背景：胆红素是一种已知的生理抗氧化剂。血红素加氧酶(HO)-1是血红素降解的限速酶，已知在肝脏、肾脏或大脑中被氧化应激诱导，但其在肠道中的诱导作用尚不清楚。我们利用大鼠脓毒症模型研究了氧化应激诱导的HO-1在肠粘膜中的表达。方法：雄性Wistar大鼠腹腔注射大肠杆菌脂多糖（LPS） （10mg/kg/体重）。分别于0、1、3、5、7.5、10和24 h处死，取小肠黏膜。测定肠黏膜还原性谷胱甘肽（GSH）、过氧化脂质、HO-1 mRNA、HO-1蛋白、胆红素和胆红素氧化代谢物（BOM）。结果：3 ~ 5 h后肠道GSH水平明显下降，降幅为对照组的40%。脂质过氧化物水平为1。5小时为对照水平的7倍。注射LPS后3 h， HO-1 mRNA水平升高至对照组的3倍，7.5 h时可检测到HO-1蛋白。胆红素水平在10小时时达到对照（峰值水平）的4倍，BOM在10小时时达到峰值水平的5倍。结论：脓毒症降低GSH含量，增加脂质过氧化物。这种肠道氧化应激诱导肠黏膜HO-1 mRNA的表达和HO-1蛋白的产生。胆红素的产生和随后氧化为BOM表明胆红素起抗氧化剂的作用。这表明，小肠在败血症中对氧化应激有快速反应的能力，而不仅仅是作为消化和吸收器官。