探讨SIRT1对脂多糖(LPS)诱导的急性呼吸窘迫综合征(ARDS)小鼠炎症反应的作用及其机制。

采用SIRT1基因敲减小鼠SIRT1^＋/－与野生型小鼠，qRT-PCR，Western Blot检测两种小鼠肺组织中的相关基因表达差异。两种小鼠用LPS腹腔注射法造模，同时设生理盐水对照组，观察肺组织病理形态学变化，测定肺湿干比(W/D比)，BCA法测定支气管肺泡灌洗液(BALF)中总蛋白浓度，ELISA法测定BALF及血浆中炎症因子TNF-α、IL-6的含量，Western Blot检测肺组织p-p38MAPK、p38MAPK、p-ATF2的表达变化。

与野生型小鼠相比，SIRT1^＋/－肺组织中SIRT1在mRNA表达和蛋白表达均显著降低，差异有统计学意义(P<0.01)。LPS致ARDS后，两种小鼠病理形态学观察均表现为肺组织炎症细胞浸润，肺泡结构破坏，间质水肿，肺泡间隔增厚，而SIRT1^＋/－小鼠肺组织破坏更严重。在SIRT1^＋/－小鼠中，肺W/D比值，BALF中总蛋白浓度，BALF及血浆中炎症因子肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)的含量，均明显高于野生型小鼠(P<0.05)，肺组织p-p38MAPK/p38MAPK、p-ATF2的表达增加也更显著(P<0.05)。

SIRT1基因在LPS致伤ARDS小鼠的炎症进程中起着非常重要的作用，其机制可能与Sirt1诱导的p38 MAPK-p-ATF2信号通路的活化增强有关。

To investigate the effect and mechanism of SIRT1 on inflammation in acute respiratory distress syndrome (ARDS) mice induced by lipopolysaccharide(LPS) .

The differences of related gene expression of lung tissues in two mice, including the SIRT1^{+ /-} mice with SIRT1 gene is knocked down and the wild-type mice, were detected by qRT-PCR and Western Blot. Then the ARDS model was induced in two kinds of mice by intraperitoneal injection of LPS, and the control group were injected with equal volume of saline. The pathological changes of lung tissue were observed by HE staining and the lung W/D ratio were calculated, the total protein concentration in BALF were detected by BCA, the levels of inflammatory factor tumour necrosis factor-α(TNF-α) and interleukin-6(IL-6) in bronchoalveolar lavage fluid (BALF) and plasma were tested by ELISA, the expression of p38 MAPK, p-p38 MAPK and p-ATF2 in lung tissue were detected by Western Blot.

Compared with wild-type mice, the mRNA and protein expression of SIRT1 in lung tissue in SIRT1^{+ /-} were significantly decreased, The difference was statistically significant(P<0.01). After ARDS induced by LPS, The pathological observation about two kinds of mice both showed infiltration of inflammatory cells in lung tissue, destruction of alveolar structure, edema of interstitial, thickening of alveolar septum, and SIRT1^{+ /-} mice were more severely damaged than wild-type mice. In SIRT1^{+ /-} mice, lung W/D ratio, total protein concentration in BALF, the levels of inflammatory factors TNF-α and IL-6 in BALF and plasma were significantly increased(P<0.05), the expression of p-p38 MAPK/p38 MAPK and p-ATF2 in lung tissues were increased more significantly than in wild-type mice(P<0.05).

The SIRT1 gene plays an important role in the inflammatory process of mice with ARDS induced by LPS, which may be related to the increased activity of p38 MAPK-p-ATF2 signaling pathway.