摘要
目的:探索原儿茶酸(protocatechuicacid,PCA)对脂多糖(lipopolysaccharide,LPS)诱导的急性肺损伤(acute lung injury,ALI)小鼠的保护作用,探讨其保护机制。方法:将40只昆明小鼠按随机数字表法均分为空白对照组(NC组)、LPS模型组、原儿茶酸预处理组(PCA+LPS组)、地塞米松阳性对照组(Dex+LPS组),每组10只,模型组以5mg·kg-1脂多糖腹腔内注射诱导急性肺损伤。6h后处死小鼠,HE染色观察肺组织病理学变化;BCA法检测肺泡灌洗液中总蛋白浓度;ELISA检测肺泡灌洗液炎症因子TNF-α、IL-1β含量;Western Blot检测肺组织中p38MAPK、p-p38MAPK、p-ATF2蛋白的表达水平。结果:与对照组相比,模型组小鼠肺损伤明显,肺泡内出血、水肿、炎细胞浸润,肺泡灌洗液中TNF-α、IL-1β的含量及总蛋白浓度增加,肺组织中p38MAPK/p-p38MAPK、p-ATF2表达均明显增加(均P<0.01)。与模型组相比,原儿茶酸预处理组、地塞米松阳性对照组肺组织病理损伤程度明显减轻,肺泡灌洗液中TNF-α、IL-1β的含量及总蛋白浓度、肺组织中p38MAPK/p-p38MAPK、p-ATF2表达均明显降低(均P<0.01)。结论:PCA对LPS诱导的急性肺损伤有保护作用,其作用机制可能与其抑制p38MAPK-p-ATF2信号通路的活化、降低肺组织炎症反应有关。
Objective: To investigate the protective effect of PCA on lung tissues during ALI in mice caused of by LPS and its possible mechanism. Methods: Forty Kunming mice were randomly divided into four groups: normal control group, LPS group, PCA pretreatment group(PCA+LPS group), dexamethasone positive control group(Dex+LPS group) with ten mice in each group. ALI was induced by intraperitoneal injection of 5mg·kg-1 LPS. Mice were sacrificed at 6 hours, the lungs were harvested for observation of pathological changes. The total protein concentration in the bronchoalveolar lavage fluid were observed by BCA method and the levels of TNF-α and IL-1β in serum of BALF were tested by ELISA. The expression of p38MAPK, p-p38MAPK, p-ATF2 in lung tissue activation were detected by Western Blotting. Results: Compared with the control group, in the model group, there were significant lung structural damage, the histological results showed pulmonary alveolar hemorrhage, edema and inflammatory cell infiltration; the expression of TNF-α, IL-1β and the total protein concentration in BALF and the expression of p38MAPK/p-p38MAPK, p-ATF2 in lung tissue were significantly increased,(all P〈0.01). Compared with the modal group, the lung histological changes were much more ameliorated, and the expression of TNF-α, IL-1β and the total protein concentration in BALF and the expression of p38MAPK/p-p38MAPK, p-ATF2 in lung tissue were markedly suppressed in PCA pretreatment group and dexamethasone positive control group(all P〈0.01). Conclusion: PCA has remarkable protective effect on ALI induced by LPS in mice,its mechanism is possibly related to the inhibition p38MAPKp-ATF2 activation and reduction of inflammatory response in the lung tissue.
出处
《现代生物医学进展》
CAS
2014年第14期2646-2649,共4页
Progress in Modern Biomedicine
基金
国家自然科学基金项目(81102828
81273037)
山东省自然科学基金(Y2007C162)