Shiyu Shu, Zhiyu Ling, Mao Ye, Lin Bo, Lijia Wang, Tianbao Zhang, Jie Chen, Tingyu Li
Department of Anesthesiology, Children's Hospital of Chongqing Medical University, Zhongshan Er Road NO136, Yuzhong District, Chongqing 40 0014, China.
BMC Cell Biol. 2011 Jul 25;12:31. doi: 10.1186/1471-2121-12-31.
Lung injury induced by lipopolysaccharide (LPS) remains one of the leading causes of morbidity and mortality in children. The damage to membrane phospholipids leads to the collapse of the bronchial alveolar epithelial barrier during acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Phospholipase A2 (PLA2), a key enzyme in the hydrolysis of membrane phospholipids, plays an important traumatic role in pulmonary inflammation, and Clara cell secretory protein (CCSP) is an endogenous inhibitor of PLA2. Our previous study showed that polydatin (PD), a monocrystalline extracted from a traditional Chinese medicinal herb (Polygonum cuspidatum Sieb, et Zucc), reduced PLA2 activity and sPLA2-IIA mRNA expression and mitigated LPS-induced lung injury. However, the potential mechanism for these effects has not been well defined. We have continued to investigate the effect of PD on LPS-induced expression of CCSP mRNA and protein in vivo and in vitro.
Our results suggested that the CCSP mRNA level was consistent with its protein expression. CCSP expression was decreased in lung after LPS challenge. In contrast, PD markedly increased CCSP expression in a concentration-dependent manner. In particular, CCSP expression in PD-pretreated rat lung was higher than in rats receiving only PD treatment.
These results indicated that up-regulation of CCSP expression causing inhibition of PLA2 activation may be one of the crucial protective mechanisms of PD in LPS-induced lung injury.
脂多糖（LPS）诱导的肺损伤仍然是儿童发病和死亡的主要原因之一。在急性肺损伤（ALI）/急性呼吸窘迫综合征（ARDS）期间，膜磷脂的损伤导致支气管肺泡上皮屏障的破坏。磷脂酶A2（PLA2）是膜磷脂水解的关键酶，在肺部炎症中起重要的创伤作用，而克拉拉细胞分泌蛋白（CCSP）是PLA2的内源性抑制剂。我们之前的研究表明，虎杖苷（PD），一种从传统中药（虎杖）中提取的单晶，降低了PLA2活性和sPLA2-IIA mRNA表达，并减轻了LPS诱导的肺损伤。然而，这些作用的潜在机制尚未明确。我们继续研究了PD在体内和体外对LPS诱导的CCSP mRNA和蛋白表达的影响。
我们的结果表明，CCSP mRNA水平与其蛋白表达一致。LPS攻击后肺中CCSP表达降低。相反，PD以浓度依赖性方式显著增加CCSP表达。特别是，PD预处理大鼠肺中的CCSP表达高于仅接受PD治疗的大鼠。
这些结果表明，CCSP表达上调导致PLA2激活受抑制可能是PD在LPS诱导的肺损伤中的关键保护机制之一。
