人硫氧还蛋白对大鼠肺缺血再灌注损伤时细胞凋亡及ASK1的影响

山东大学学报(医学版) ›› 2010, Vol. 48 ›› Issue (7): 19-.

人硫氧还蛋白对大鼠肺缺血再灌注损伤时细胞凋亡及ASK1的影响

倪世容1，王万铁1，王鑫2，郝卯林1，戴雍月1

1.温州医学院病理生理教研室, 浙江温州 325027； 2.温州市第二人民医院妇产科，浙江温州 325027

收稿日期:2009-11-19 出版日期:2010-07-16 发布日期:2010-07-16

Effects of human Thioredoxin on pneumocyte apoptosis and ASK1 expression in rats with lung ischemia/ reperfusion injury

NI Shirong1, WANG Wantie1, WANG Xin2, HAO Maolin1, DAI Yongyue1

1. Department of Pathophysiology, Wenzhou Medical College, Wenzhou 325027, Zhejiang, China;
2. The Second People′s Hospital of Wenzhou City , Wenzhou 325027, Zhejiang, China

Received:2009-11-19 Online:2010-07-16 Published:2010-07-16

摘要/Abstract

摘要：

目的探讨细胞凋亡与肺缺血再灌注损伤的关系及人硫氧还蛋白的作用机制。方法随机将Wistar大鼠84只分为对照组、肺缺血再灌注组、人硫氧还蛋白干预组。观察各组肺组织湿、干重比值（W/D）、肺泡损伤指数（IQA）、肺组织超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量，采用原位缺口末端标记(TUNEL)法观测细胞凋亡指数(AI）, 采用免疫组化技术检测细胞凋亡信号调节激酶1(ASK1)蛋白的变化。结果与对照组比较,缺血再灌注组SOD活性降低,MDA含量、W/D比值、IQA、AI及ASK1表达均上调(P均<0.01)。与缺血再灌注组比较, 人硫氧还蛋白干预组SOD活性显著升高,MDA、W/D比值、IQA、AI及ASK1表达明显下降(P均<0.01)。AI与SOD、ASK1蛋白与SOD呈显著负相关(r为-0.820,-0.749，P均<0.01), 与W/D、IQA、MDA、ASK1蛋白呈明显正相关(r分别为0.721,0.835,0.844,0.675, P均<0.01)，与MDA含量呈明显正相关（r为0.721,P<0.01）。结论肺组织细胞凋亡参与肺缺血再灌注损伤的发生，人硫氧还蛋白可能通过降低氧自由基水平、减轻脂质过氧化反应，下调ASK1的表达抑制细胞凋亡，从而减轻肺缺血再灌注损伤。

关键词: 肺；再灌注损伤；细胞凋亡；硫氧还蛋白；凋亡信号调节激酶1

Abstract:

Objective To investigate the relationship between oxidative stress and apoptosis in lung ischemia/reperfusion injury, and to observe the inhibitory effects of human Thioredoxin in lung ischemia/reperfusion injury. Methods Single lung in situ ischemia/reperfusion animal model was used. Eighty four Wistar rats were randomly divided into control group, ischemia / reperfusion group and human Thioredoxin group. Lung tissue was taken to measure the ratio of wet to dry lung tissue weight (W/D）, index of quantitative assessment of histologic lung injury (IQA), activity of superoxide dismutase (SOD) and content of malondialdehyde (MDA). Terminal deoxynucleotidyl transferase dUTP nick end labeling and immunocytochemistry techniques were used to observe the pneumocyte apoptosis index (AI) and apoptosis signal-regulating kinase 1 (ASK1) expression in various phases of lung ischemia/reperfusion. Results The activity of SOD showed a time-dependent decrease in the ischemia / reperfusion group (P<0.01), while the content of MDA, values of W/D, IQA and AI , and expression of ASK1 were gradually increased with the time of reperfusion prolonging in lung tissues of lung ischemia/ reperfusion injury compared with the control group (all P<0.01). The hTrx suppressed apoptosis as well as expression of ASK1 and the contents of MDA， W/D and IQA (P<0.01). There was a negative correlation between AI and SOD (r=-0.820, P<0.01). There were significant correlations between W/D, IQA, MDA, ASK1 protein, and AI (r=0.721, 0.835, 0.844, 0.675, respectively; all P<0.01). ASK1 protein was negatively correlated with SOD activity (r=-0.749, P<0.01), and positively correlated with MDA content (r=0.721, P<0.01). Conclusions Activation of ASK1 and its initiation on cell apoptosis of lung tissues and oxidative stress may contribute to the pathogenesis of lung ischemia/reperfusion injury. The protective effects of hTrx include suppressing lipoperoxide reaction and down-regulating the expression of ASK1 and blocking apoptosis in lung tissues of lung ischemia/reperfusion injury.

Key words: Lung; Reperfusion injury; Apoptosis; Thioredoxin; Apoptosis signalregulating kinase1

中图分类号:

R363

倪世容1，王万铁1，王鑫2，郝卯林1，戴雍月1 . 人硫氧还蛋白对大鼠肺缺血再灌注损伤时细胞凋亡及ASK1的影响[J]. 山东大学学报(医学版), 2010, 48(7): 19-.

NI Shirong1, WANG Wantie1, WANG Xin2, HAO Maolin1, DAI Yongyue1 . Effects of human Thioredoxin on pneumocyte apoptosis and ASK1 expression in rats with lung ischemia/ reperfusion injury[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2010, 48(7): 19-.

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