西格列汀预处理对大鼠肺缺血再灌注损伤保护机制的研究

Study of the protective mechanism of sitagliptin pretreatment on lung ischemia-reperfusion injury in rats

目的:探讨西格列汀对大鼠肺缺血再灌注损伤(LIRI)的作用。方法:通过夹闭左肺动脉30min后松开的方法,创建肺组织缺血再灌注损伤模型。设立空白对照组(Sham组),对照组(I/R组),实验组(sitagliptin组),将30只,SD大鼠,随机分组,每组10只,检测各组肺组织的湿干比(W/D);HE染色光镜下比较各组肺组织病理改变;测定丙二醛(MDA)含量和抗氧化酶(SOD、GSH-Px)活性;测定NF-κB蛋白含量。结果:与假手术组对比,缺血再灌注组和西格列汀组的肺组织W/D、MDA、NF-κB含量升高,SOD、GSH-Px活性降低,而且肺组织病理也有明显变化;与缺血再灌注组对比,西格列汀组的肺组织W/D、MDA、NF-κB含量较低,SOD、GSH-Px活性较高,肺组织病理改变更轻。结论:西格列汀可减轻肺组织缺血再灌注损伤病理改变,并可能通过抑制NF-κB蛋白表达,减轻炎症反应和氧化应激,从而减轻大鼠的肺缺血再灌注损伤。

Objective:To verify the effect of sitagliptin pretreatment on lung ischemia-reperfusion injury(LIRI)in mice.Methods:Thirty mice were randomly divided into three groups in ten of each group including Sham group,I/R group,and sitagliptin group.sham and I/R group received 2 mL/kg of 0.9%sodium chloride solution daily for 7d.Sitagliptin group received 30 mg/kg sitagliptin for 7d continuously dissolve into 0.9%sodium chloride solution for 2 mL/kg.On the 8th day,Sham group underwent tracheotomy under anesthesia and opened left chest only without performing ischemia and reperfusion;the other two groups prepared the lung ischemia and reperfusion model by using left lung artery clipping.Rats were sacrificed 2h later.Removed their left lungs.Measured the wet/dry weight ratio(W/D)of lung tissue;observed the lung tissues by HE staining;determined the MDA content,the activities of SOD,GSH-Px,and the expression of NF-κB.Results:Compared with the sham group,there are significant differences in the W/D,MDA,NF-B content,and the activity of SOD,GSH-Px.Moreover,the differences between the sitagliptin group and I/R groups were also statistically significant,with lighter pathological changes in the Sitagliptin group.Conclusions:Sitagliptin can downregulate NF-κB protein expression and inhibit inflammatory response and oxidative stress to reduce lung injury caused by lung ischemia and reperfusion.