姜黄素衍生物对脂多糖诱导急性肺损伤的防护作用研究

Curcumin derivative protects mouse from acute lung injury induced by lipopolysaccharide

目的对姜黄素衍生物是否可治疗脂多糖(LPS)诱导的急性肺损伤(ALI)进行研究,为研究姜黄素衍生物的作用机制及临床应用提供参考。方法小鼠腹腔注射LPS复制ALI模型,昆明小鼠90只,随机分为6组,分别为正常组、模型组、姜黄素组,以及姜黄素衍生物低、中、高剂量组(50、100和200 mg/kg)。预先7 d给予小鼠灌胃治疗,第7天小鼠腹腔注射10 mg/kg LPS。分别于6 h、1 d和3 d取材,检测血中中性粒细胞和单核细胞的比例变化。酶联免疫吸附试验检测小鼠肺组织中炎症因子白介素6(IL-6)和肿瘤坏死因子α(TNF-α)的含量;丙二醛、髓过氧化物酶及谷胱甘肽试剂盒检测小鼠肺组织中氧化物质的含量。肺组织苏木精-伊红染色法(HE)染色观察肺组织病理改变。结果姜黄素衍生物可减少小鼠血中炎症细胞数,降低小鼠肺组织中炎症因子。肺组织HE染色结果显示,模型组肺组织切片炎症细胞增多,肺泡壁增厚,肺泡结构破坏,而姜黄素衍生物各剂量组与模型组比较,差异有统计学意义(P<0.05)。结论姜黄素衍生物对内毒素诱导的ALI有一定的保护作用。

Objective To investigate the protective and therapeutic effect of curcumin derivative onlipopolysaccharide -stimulated acute lung injury （ALI） in mice so as to provide reference for the study onmechanism and clinic application of curcumin derivative. Methods The mouse model of ALI was built by intra-peritoneal injection of lipopolysaccharide （LPS）. Ninety Kunming mice were randomly divided into 6 groups （each with 15）： normal control, ALI, curcumin （100mg/kg）, curcumin derivative （50, 100 and 200mg/kg） groups. The mice were pretreated with gavage of different medicines for 7 days, and had intraperitoneal injection of LPS （10 mg/kg） on the 7th d. The changes of proportions of neutrophils and monocytes in blood were detected 6h, 1 and 3d after establishment of the model, meanwhile, the content of malondialdehyde （MDA）, myelo-peroxidase （MPO） and glutathione （GSH） in the lung tissues was tested and histological changes of the lungs were observed. The expressions of TNF-α and IL -6 in the lung tissues were measured by ELISA. Results Thecurcumin derivative reduced the number of inflammatory cells in blood and lowered the production of inflam-matory factors. Histological studies showed that there were congestion, edema and infiltration of inflammatory cells in the lung tissues of the ALI group. Compared with the ALI group, the histological changes were im-proved greatly in the curcumin derivative groups （P〈0.05）. Conclusions Curcumin derivative can protect mice from ALI induced by LPS, the mechanism will be studied in the next experiment.