内质网应激诱导的细胞凋亡在大鼠肢体缺血再灌注后肺损伤中的作用及牛磺酸的影响  

Effects of taurine on endoplasmic reticulum stress-induced cell apoptosis in lung inury following limbs ischemia reperfusion in rats

作　　者：成兰云[1] 门秀丽[1] 张连元[1] 李宏杰[1] 孔小燕[1] 赵利军[1] 

机构地区：[1]华北煤炭医学院病理生理学教研室,河北唐山063000

出　　处：《中国病理生理杂志》2010年第9期1776-1780,共5页Chinese Journal of Pathophysiology

基　　金：河北省教育厅科研基金资助项目(No2001135)

摘　　要：目的:探讨内质网应激诱导的细胞凋亡在大鼠肢体缺血再灌注(LIR)后肺损伤中的作用及牛磺酸的影响。方法:成年雄性SD大鼠40只,随机分成4组:(1)对照组(control);(2)LIR组;(3)牛磺酸处理组(LIR+taurine);(4)生理盐水处理组(LIR+saline)。采用生物化学方法检测血气变化及肺组织超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和丙二醛(MDA)含量;采用原位末端标记(TUNEL)法观察肺组织细胞凋亡情况;采用蛋白质印记方法(Westernblotting)及实时定量PCR(real-timePCR)方法观察LIR后肺损伤发生过程中CCAAT增强子结合蛋白(C/EBP)同源蛋白(CHOP)及活化的转录因子4(ATF4)和X-盒结合蛋白-1(XBP1)基因表达的改变;光镜下观察肺脏组织的形态学改变。结果:与对照组相比,LIR组的动脉血氧分压(PaO2)和动脉血二氧化碳分压(PaCO2)明显下降,肺组织中MDA水平明显升高,SOD和CAT活性明显降低,细胞凋亡数增多,CHOP蛋白表达上调,XBP-1、ATF4和CHOPmRNA表达水平明显上调;而牛磺酸能明显减轻LIR后肺损伤;肺呼吸功能明显改善,肺组织MDA的含量减少,SOD和CAT活性增加,细胞凋亡明显减少,CHOP蛋白表达下调,ATF4、XBP1和CHOP基因表达下调。结论:内质网应激诱导的细胞凋亡参与LIR后肺损伤,牛磺酸对LIR后肺组织的保护作用与其减轻内质网应激诱导的细胞凋亡有关。AIM： To investigate the role of endoplasmic reticulum stress （ ERS）-induced apoptosis in lung injury following limbs ischemia reperfusion （ LIR） in rats and to observe the effects of taurine. METHODS： Adult male Sprague-Dawley rats （ n = 40） were randomly divided into 4 groups： control group,LIR group,LIR ＋ saline group and LIR ＋ taurine group. The changes of blood gas,the activity of superoxide dismutase （ SOD） and catalase （ CAT） ,and the level of malondialdehyde （ MDA） were detected by biochemical methods. Apoptosis in lung tissues was observed using TdT-mediated dUTP nick end labeling （ TUNEL） assay. The mRNA expression of C/EBP homologous protein （ CHOP） ,activating transcription factor 4 （ ATF4） and X-box binding protein 1 （ XBP1） in the lung tissues was observed by real-time PCR. The protein level of CHOP in the lung tissues was detected by Western blotting. The morphologic changes of the lung tissues were observed under microscope. RESULTS： Compared with control group,PaO2 and PaCO2 in LIR group were reduced,and MDA content was increased. The activity of SOD and CAT was decreased. The cell apoptosis was increased. The protein level of CHOP and mRNA expression of ATF4,XBP1 and CHOP were upregulated. However,taurine significantly attenuated the lung injury following LIR,as showed by reducing the MDA content,decreasing cell apoptosis and inhibiting the mRNA expression of ATF4,XBP1 and CHOP. Furthermore,PaO2 and the activity of SOD and CAT were higher in taurine pretreatment group than those in LIR group. CONCLUSION： The results suggest that taurine attenuates ERS-induced apoptosis in the lungs of the rats with limb ischemia reperfusion.

关 键 词：内质网应激 细胞凋亡 肺损伤 缺血再灌注 牛磺酸 

分 类 号：R563[医药卫生—呼吸系统]