姜黄素对百草枯致大鼠急性肺损伤中Egr—1mRNA、IL-1β、TNF-α的影响

Effects of curcumin on changes of Egr-lmRNA, IL-1β and TNF-a in paraquat-induced acute lung injury in rats

目的观察百草枯（PQ）致急性肺损伤模型中早期生长反应因子-1mRNA（Egr-1mRNA）、白介素-1β（IL-1β）、肿瘤坏死因子-仪（TNF-仅）的变化以及姜黄素的干预作用。方法成年雄性SD大鼠随机（随机数字法）分成对照组、中毒组、干预组，各组再按3h、6h、24h、3d、7d时间点5个亚组。中毒组腹腔注射PQ15mg／kg，干预组腹腔注射姜黄素200mg／kg15min后腹腔注射PQ15mg／kg，对照组腹腔注射生理盐水1mL。荧光实时定量PCR法测定各组大鼠肺组织中Egr-1mRNA表达量，ELISA法测定各组支气管肺泡灌洗液（BALF）中白介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）水平，光镜下观察各组肺组织病理变化。实验数据统计采用单因素方差分析，组间比较用βonferroni法。结果与对照组比较，中毒组和干预组肺组织Egr-1mRNA表达量和BALF中TNF—d水平、中毒组βALF中IL-1β水平在染毒后6h、24h、3d、7d均明显升高（P〈0．05或P〈0．01），干预组BALF中IL-1β水平在染毒后24h明显升高（P〈0．05）；与中毒组比较，干预组肺组织Egr-1mRNA表达量、BALF中IL-1β和TNF-α水平在染毒后24h、3d、7d均明显下降（P〈0．05或P〈0．01）；中毒组病理改变严重，干预组病理改变较中毒组减轻。结论肺组织Egr-1mRNA表达上调，TNF-α、IL-1β释放增加，参与启动炎症反应，可能是PQ中毒急性肺损伤的机制之-，姜黄素可能通过此信号通路减轻肺损伤的程度。

Objective To observe the changes of early growth response factor-1 mRNA （Egr-1 mRNA）, interleukin-lβ （IL-Iβ） and tumor necrosis factor-a （TNF-a） in rat with paraquat （PQ） - induced acute lung injury, and the potential protective effect of curcumin on this injury. Methods Adult male Sprague-Dauley （SD） rats were randomly （random number） divided into control, PQ-poisoning and curcumin-intervention groups. At 3 h, 6 h, 24 h, 3 d, 7 d after treatment, each group respectively further divided into 5 subgroups. Rats in PQ-poisoning group were intraperitoneally （IP） administered with PQ 15 mg/kg, and rats in curcumin-intervention group were administered with PQ 15 mg/kg IP at 15 min after curcumin 200 mg/kg IP. Rats in control group were given normal saline （NS） 1 mL IP instead. The expression of Egr-1 mRNA in lungs tissue were measured with Fluorescence real-time quantitative PCR device. The levels of IL-β and TNF-a in bronchoalveolar lavage fluid （BALF） were measured withenzyme-linked immunosorbent assay （ELISA）. Pathological changes in lung were observed under light microscope. Experimental data were treated with single-factor analysis of variance and compared between groups with Bonferroni method. Results Compared with the control group, Egr-1 mRNA expression in lungs tissue and TNF-a level in BALF in PQ-poisoning group and curcumin-intervention group, IL-113 level in BALF in PQ-poisoning group increased significantly at 6 h, 24 h, 3 d, 7 d after PQ exposure （P 〈 0. 05 or P 〈 0. 01 ）, and IL-Iβ level in BALF increased significantly at 24 h after PQ exposure in curcumin- intervention group （P 〈 0.05 ）. Compared with the PQ-poisoning group, Egr-1 mRNA expression in lungs tissue, TNF-a and IL-1βlevel in BALF decreased significantly at 24 h, 3 d, 7 d after PQ exposure in curcumin-intervention group （P 〈 0. 05 or P 〈 0.01 ）. Pathological changes of lung tissue were more serious in PQ-poisoning group than those in curcumin-intervention group. Conclusions The up-regulated expression of Egr-1 mRNA increased releasing of IL-1β and TNF-a, and initiating inflammation may be one of the mechanism of PQ-induced acute lung injury in rats. Curcumin may have beneficial protective effects on lung in this above described pathway of signaling.