血红素氧合酶-1对心力衰竭大鼠肠道炎症的保护机制

Protective mechanism of heme oxygenase-1 on intestine in heart failure rats by suppression of intestinal inflammation

目的：研究血红素氧合酶-1（HO-1）对心力衰竭（心衰）大鼠肠道炎症的保护机制。方法通过冠状动脉结扎术造成心肌梗死建立心衰大鼠模型（雄性，Wistar大鼠），每组10只，分为心肌梗死（MI）模型组、MI＋钴-原卟啉（MI＋Copp）组、MI＋锡中卟啉（MI＋SnMP）组，以正常大鼠作为对照组，分别腹腔注射生理盐水、Copp溶液、SnMP溶液。8周后取门静脉及下腔静脉血检测血浆内毒素含量，通过Western印迹测定小肠HO-1的表达，比色法测定小肠一氧化碳（CO）浓度，酶联免疫吸附法测定小肠肿瘤坏死因子-α和白细胞介素-10水平。结果与MI组比较，MI＋Copp组HO-1和CO水平明显升高，血浆内毒素含量减少，肠道炎症减轻，而MI＋SnMP组HO-1无明显变化，CO明显降低，血浆内毒素浓度升高，小肠炎症加重。结论 HO-1可抑制心衰大鼠肠道炎症，该作用可能与CO有关。

Objective To investigate the underlying mechanism through which heme oxygenase-1 （HO-1） protects intestine against inflammation in rats with heart failure. Methods Heart failure model was established in male Wistar rats by myocardial infarction （MI） with coronary ligation. These model rats were randomized into 3 experimental groups （10 rats in each group）：Myocardial infarction （MI）, MI＋cobalt protoporphyrin（Copp）, and MI＋stannum＋mesoporphyrin Ⅸ dichloride （SnMP;a HO-1 inhibitor） groups, receiving intra-peritoneal injection of saline, cobalt protoporphyrin solution, and stannum mesoporphyrin Ⅸ dichloride solution, respectively. Another 10 rats served as normal controls and received intraperitoneal injection of normal saline. After 8 weeks, the endotoxin level in portal vein and inferior vena cava, the expression of HO-1, and the contents of carbon monoxide （CO）, tumor necrosis factor （TNF）-α, and interleukin-10 in the intestine were determined by Western blotting, colorimetry, and enzyme-linked immunosorbent assay （ELISA）. Results Compared with MI group, MI＋Copp group had significantly elevated HO-1 and CO expression, reduced endotoxin, milder inflammation in the intestine, and these benefits were abolished by SnMP, with obviously decreased CO, elevated endotoxin and severer intestinal inflammation. Conclusion HO-1 suppresses intestinal inflammation, which may be associated with CO.