摘要
目的:观察二甲基精氨酸二甲胺水解酶2(dimethylarginine dimethylaminohydrolase 2,DDAH2)在糖尿病脓毒症机体中的表达变化,探讨血管内皮功能损害的发生机制。方法:64只Wistar大鼠随机分为正常对照组、单纯脓毒症组、糖尿病组、糖尿病脓毒症组,每组16只。免疫组织化学方法观察肺组织结构变化及DDAH2表达的分布变化。Griess法测定血清及肺组织一氧化氮(nitrite oxide,NO)含量,real-time PCR测定肺组织DDAH2 mRNA水平。结果:免疫组织化学显示糖尿病组大鼠肺组织平均光密度值(average optical density value,AOV)无明显变化,RT-PCR显示DDAH2 mRNA表达水平低于正常对照组(P<0.05);脂多糖(lipopolysaccharides,LPS)腹腔注射后,单独脓毒症组和糖尿病脓毒症组肺组织DDAH2 AOV值及mRNA表达较正常对照组均明显降低(均P<0.01);且糖尿病脓毒症组AOV值低于单纯脓毒症组(P<0.01),DDAH2 mRNA表达亦低于单纯脓毒症组(P<0.05)。糖尿病脓毒症组及单纯脓毒症组血清及肺组织中NO水平均增高,血清测定前者低于后者(P<0.05),但肺组织中前者高于后者近2倍(P<0.05)。结论:脓毒症肺表现为DDAH2表达下调,糖尿病脓毒症肺组织表现为DDAH2表达更为明显下调,提示存在更为严重的血管内皮细胞损害,因此DDAH2表达下调可能参与脓毒症糖尿病机体肺损伤的发生。
Objective： To investigate the changes in dimethylarginine dimethylaminohydrolase 2 （DDAH2） expression in lung of diabetic rat with sepsis and to explore the mechanisms behind endothelial damage. Methods： Sixty-four Wistar rats were randomly divided into 4 groups： a normal control group, a diabetes group, a sepsis group and a diabetes plus sepsis group （each group n=16）. The structure changes of lung and the expression of DDAH2 was measured by immunohistochemistry, the level of NO in serum and lung was measured by Griess assay and the mRNA expression of DDAH2 was detected by real-time PCR. Results： Compared to the control, DDAH2 mRNA expression in lung tissues was decreased in the diabetes group （P〈0.05）; the immunohistochemistry results showed that there was no significance change in the average optical density （AOD） value in lung tissues among groups, but after LPS injection the AOD value as well as DDAH2 mRNA level in the sepsis group and the diabetes plus sepsis group were significant lower than that in the normal control group（all P〈0.01）.The AOV value and DDAH2 mRNA level in the diabetes plus sepsis group decreased much more than that in the sepsis group （P〈0.01）. NO levels in serum and lung in the diabetes plus sepsis group and the sepsis group increased significantly compared with that in the normal control group. Serum level of NO in the diabetes plus sepsis group was lower than that in the sepsis group （P〈O.OS）, but NO contents in lung tissue in the diabetes plus sepsis group was the 2 times of that in the sepsis group （P〈0.05）. Conclusion： DDAH2 expression in lung is reduced under the condition of sepsis, and it is decreased much more under the condition of sepsis plus diabetes.The reduced DDAH2 expression indicates the endothelial damage and it may be involved in the pathogenesis of lung iniury caused by diabetic sepsis.
出处
《国际病理科学与临床杂志》
CAS
2013年第5期379-384,共6页
Journal of International Pathology and Clinical Medicine
基金
高等学校博士学科点专项科研基金(20102104110003)~~
