Wang W-Y, Chen Y, Su X, Tang D, Ben Q-W, Yao W-Y, Chen P, Yuan Y-Z
Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University, 197 Ruijin Er Rd, Shanghai 200025, China.
Curr Mol Med. 2016;16(7):677-687. doi: 10.2174/1566524016666160802145700.
Resistin-like molecule-α (RELMα) has diverse regulatory functions in inflammation, but its role in severe acute pancreatitis (SAP) and acute pancreatitis associated lung injury (APALI) remains unclear.
SAP was induced in rats. RELMα protein expression was detected in lung tissue of rats to determine the relationship between APALI and RELMα. To investigate the effect of RELMα overexpression or knockdown on APALI, rats were given an intravenous injection of adenovirus vector before SAP induction. Lung and pancreatic samples were harvested 16 h after induction. After detection of RELMα protein levels, the severity of pancreatic and pulmonary injury was scored histologically, and serum and tissue levels of inflammatory mediators were measured. TUNEL assay and immunofluorescence were used to estimate pulmonary apoptosis and endothelial barrier integrity in lung tissue of SAP rats with RELMα knockdown.
RELMα expression was significantly up-regulated in APALI and was related to the lung injury index. RELMα overexpression aggravated the release of inflammatory cytokines including interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor-α, and serum C-reaction protein; the expression of inflammatory mediators phosphorylated (p)-AKT, p-P65, p-P38 mitogen activated protein kinase, p-extracellular regulated kinase, and intracellular adhesion molecule-1; and lung injury. RELMα knockdown had opposite effects. In addition, RELMα knockdown improved expression of proliferative cellular nuclear antigen, Bcl-2, zonal occluding-1 and Claudin-1 in lung tissue of SAP rats.
RELMα is associated with lung injury severity in SAP. RELMα augments inflammatory activity by increasing inflammatory cytokine release.
抵抗素样分子α（RELMα）在炎症中具有多种调节功能，但其在重症急性胰腺炎（SAP）及急性胰腺炎相关性肺损伤（APALI）中的作用仍不清楚。
诱导大鼠发生SAP。检测大鼠肺组织中RELMα蛋白表达，以确定APALI与RELMα之间的关系。为研究RELMα过表达或敲低对APALI的影响，在诱导SAP前给大鼠静脉注射腺病毒载体。诱导16小时后采集肺和胰腺样本。检测RELMα蛋白水平后，对胰腺和肺损伤的严重程度进行组织学评分，并测定血清和组织中炎症介质的水平。采用TUNEL法和免疫荧光法评估敲低RELMα的SAP大鼠肺组织中的肺细胞凋亡及内皮屏障完整性。
APALI中RELMα表达显著上调，且与肺损伤指数相关。RELMα过表达加重了包括白细胞介素（IL）-1β、IL-6、IL-8、肿瘤坏死因子-α和血清C反应蛋白在内的炎症细胞因子的释放；炎症介质磷酸化（p）-AKT、p-P65、p-P38丝裂原活化蛋白激酶、p-细胞外调节激酶和细胞间黏附分子-1的表达；以及肺损伤。RELMα敲低则产生相反的效果。此外，RELMα敲低改善了SAP大鼠肺组织中增殖细胞核抗原、Bcl-2、紧密连接蛋白1和闭合蛋白1的表达。
RELMα与SAP中的肺损伤严重程度相关。RELMα通过增加炎症细胞因子释放增强炎症活性。
