重症胰腺炎并急性肺损伤大鼠肺组织蛋白激酶C与细胞外信号调节激酶的表达

Expression of protein kinase C and extracellular signal regulated protein kinase in severe pancreatilis rats with acute lung injury

目的探讨重症胰腺炎并急性肺损伤大鼠肺组织蛋白激酶C（PKC）与细胞外信号调节激酶（ERK）的表达及意义。方法健康成年雄性SD大鼠40只，随机分为对照组（n=8）与胰腺炎组，胰腺炎组再按6、12、24、48h分（B1、B2、B3、B4）亚组。以大鼠重症胰腺炎所致ALI为模型，采用酶联免疫吸附（ELISA）法检测血清TNF-α、IL-1β及IE-6，Western blot检测肺组织PKC与ERK的蛋白表达，EMSA检测NF-κB活性变化，观察肺脏含水量、肺脏病理变化。结果内毒素致重症胰腺炎并发急性肺损伤早期即发生肺血管通透性增高，肺脏含水量上升，组织学显示肺脏出现明显的病理损害，血清TNF-α、IL-1β及IL-6增高，肺组织PKC、ERK与NF-κB DNA活性同步增强。结论PKC与ERK的活化参与了重症胰腺炎时ALI的发病，即ERK／NF-κB信号通路的活化。

Objective To investigate the expression of protein kinase C （PKC） and extracellular signal regulated protein kinase （ERK） in the lung tissue of rats with severe pancreatitis and acute lung injury. Method Forty healthy male Sprague-Dawley rats were randomly divided into control group （n = 8 ） and severe pancreatitis with acute lung injury group, and the latter group was divided into four subgroups at 6 hours, 12 hours, 24 hours and 48 hours, respectively. Severe-pancreatitis-induced acute lung injury models were induced by lipopolysaccharide （LPS）. The expression of TNF-α , IL- 19 and IL- 6 in serum, protein levels of PKC and ERK and activity of NF-κB DNA in lung tissue were detected by enzyme-linked immunosorbent assay （ ELISA）, western blotting and electrophoretic mobility shift assay （EMSA）, respectively. Pathological changes and water content of lung tissue were also observed. Results In comparison with control group, the blood vessel penetrability and water content in lung tissue were increased, pathological changes of lung tissue were aggravated significantly, the activity of PKC, ERK and NF-κB DNA were synchronously elevated in lung tissue as the serum levels of TNF-α, IL-1β and IL-6 increased at early stage of severe-pancreatitis-induced acute lung injury. Conlusions Activation of PKC and ERK are found to participate in the pathological process of severe-pancreatitis-induced acute lung injury through the activation of ERK/NF-κB signal pathway.