异甘草酸镁上调血红素氧合酶-1对巨噬细胞过度分泌炎症因子的作用研究

doi:10.3969/j.issn.1002-1949.2017.11.004

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摘要目的：探讨异甘草酸镁（MgIG）在脂多糖（LPS）刺激的RAW264.7巨噬细胞中是否能通过上调血红素氧合酶-1（HO-1）起到抑制高迁移率族蛋白B1（HMGB1）和一氧化氮（NO）释放的作用。方法：用LPS刺激小鼠巨噬细胞RAW264.7制作炎症细胞模型。①先用不同浓度的MgIG与LPS合并处理24 h，分别为Control组、LPS组和LPS+MgIG不同剂量组（0.01 mg/mL、0.10 mg/mL、0.50 mg/mL和1.00 mg/mL）；②再将培养细胞随机分为不同处理组(每组n=5)：Control 组、LPS组、LPS+MgIG（1.00 mg/mL）和LPS+MgIG（1.00 mg/mL）+血红素氧化酶抑制剂［ZnPPIX（10 μmol/L）］组。用ELISA方法测定上清HMGB1浓度，用Griess法测定上清液NO的浓度水平，用Western bolt 检测细胞内HO-1和iNOS蛋白的表达。结果： ①与Control组比较，LPS能够明显增加上清液HMGB1和NO浓度(均P＜0.05)，并且在一定程度上增加细胞内HO-1的蛋白表达水平(P＜0.05)；与LPS组比较，LPS+MgIG不同剂量组均减少了HMGB1和NO的释放(均P＜0.05)，并且随着剂量的增加，HMGB1和NO的上清液水平降低越明显，而HO-1的表达水平在LSP+MgIG（0.10 mg/mL、0.50 mg/mL和1.00 mg/mL）组均明显诱导增加 (均P＜0.05)。②与Control比较，LPS同样明显增加上清液HMGB1和NO浓度(均 P＜0.05)，以及明显增加细胞内HO-1和可诱导一氧化氮合酶（iNOS）蛋白表达水平(均P＜0.05)；与LPS组比较，LPS+MgIG（1.00 mg/mL）组上清液中HMGB1和NO浓度明显下降(均P＜0.05)，细胞内HO-1的蛋白水平明显增加 (P＜0.05)，细胞内iNOS的蛋白水平则明显下降 (P＜0.05)，而LPS+MgIG（1.00 mg/mL）+ ZnPPIX（10 μmol/L）组上清液HMGB1和NO浓度、细胞内HO-1和iNOS的蛋白水平差异均无统计学意义(均P＞0.05)。结论： MgIG能抑制LPS刺激巨噬细胞过度释放HMGB1和NO，能明显抑制LPS诱导的iNOS表达，并且依赖于HO-1的上调。

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	张磊
	蒋磊
	张丽坤
	龚睿
	潘尚哈
	赵鸣雁

收稿日期: 2017-05-16

基金资助:黑龙江省自然科学基金(ZJY0704-02)；国家自然科学基金(81171785) ；哈尔滨医科大学研究生创新科研项目（YJSCX2015-21HYD）

通讯作者: 赵鸣雁（1970-），女，医学博士，博士后，教授，博士生导师，主任医师，ICU主任，E-mail: mingyan1970@163.com。

作者简介: 张磊（1980-），男，硕士，主治医师。

引用本文:

张磊，蒋磊，张丽坤，龚睿，潘尚哈，赵鸣雁. 异甘草酸镁上调血红素氧合酶-1对巨噬细胞过度分泌炎症因子的作用研究[J]. 中国急救医学, 2017, 37(11): 983-987.
Zhang Lei, Jiang Lei, Zhang Li-kun, Gong Rui, Pan Shang-ha, Zhao Ming-yan. Magnesium isoglycyrrhetate inhibits the over-release of inflammatory mediators in LPS-stimulated macrophages through up-regulating heme oxygenation-1. Chinese Journal of Critical Care Medicine, 2017, 37(11): 983-987.

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http://www.cnemergency.org.cn/CN/10.3969/j.issn.1002-1949.2017.11.004 或 http://www.cnemergency.org.cn/CN/Y2017/V37/I11/983

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