钙调蛋白依赖性激酶Ⅱ在脂多糖诱导的脓毒症致急性呼吸窘迫综合征膈肌功能障碍中的作用

Role of CaMKⅡ in diaphragm dysfunction caused by LPS-induced ARDS

目的研究钙调蛋白依赖性激酶Ⅱ(Calcium/calmodulin-dependent protein kinase Ⅱ,CaMKⅡ)在脂多糖(lipopolysaccharides,LPS)诱导的急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS)大鼠膈肌中的表达,并探讨其在LPS致脓毒症诱导的ARDS膈肌功能障碍中的作用。方法采用LPS腹腔注射构建大鼠ARDS模型,通过实时荧光定量聚合式酶链反应(real-time PCR)检测ARDS模型组及正常大鼠组膈肌组织CaMKⅡmRNA的表达情况。结果 (1)CaMKⅡ三种亚型2b、2d、2g在正常大鼠膈肌组织中均有表达,其中CaMKⅡ2b表达最少(P<0.05);(2)CaMKⅡ2b、2d、2g在ARDS组表达均比对照组高(P <0.05),在48 h组均显著上调(P<0.05),其中CaMKⅡ2b亚型表达最高(P<0.05)。结论 CaMKⅡ在大鼠膈肌组织中有表达,并在LPS诱导的ARDS致膈肌功能障碍中发挥重要作用,其中CaMKⅡ2b亚型可能参与主要作用。

Objective To investigate the expression of Calmodule-dependent Kinase Ⅱ in diaphragmatic muscle of rats with lipopolysps-induced acute respiratory distress syndrome(ARDS) and the effection on ARDS with diaphragm dysfunction induced by LPS.Methods The rat model of ARDS was established by intraperitoneal injection of LPS.Real-time PCR was used to study the expression of CaMKⅡ mRNA in the diaphragm tissues of both the model group(rats with ARDS) and the normal one.Results(1)The three subtypes of CAMKⅡ,2b,2d,and 2g,were all expressed in diaphragm tissues of the normal rats,among which CAMKⅡ 2b subtype was least expressed(P <0.05);(2)Compared with the normal rats,the expression of CAMKⅡ 2b,2d,and 2g mRNA in the rats ARDS were all up-regulated(P <0.05);while other different subtypes of CAMKⅡ mRNA expression were significantly up-regulated in the group with ARDS for 48 hs(P <0.05),and the mRNA expression of the CAMKⅡ2b subtype was among the top,compared with other subtypes(P <0.05).Conclusion CAMKⅡ has been expressed in diaphragm tissues of rats and played an important role in ARDS with diaphragm dysfunction induced by LPS,and among them CAMKⅡ 2b subtype may play a key role in this process.