| 摘要: |
| 目的探讨促红细胞生成素后处理在减轻肺缺血/再灌注损伤（LIRI）大鼠肺细胞凋亡中的作用及其机制。方法健康雄性成年SD大鼠40只，按随机数字表法分成5组，每组8只，即假手术对照组（C组）、缺血/再灌注(IR)组、促红细胞生成素（EPO）组、EPO+溶剂对照组（PPCES溶液）（P组）和EPO+SP600125（SP组），通过阻断左肺门制作动物模型并予相应处理。原位末端标记法（TUNEL）检测肺细胞凋亡情况并计算凋亡指数（AI）；RT-PCR法、免疫组化法测定肺组织Bcl-2、Bax基因和蛋白的表达；光镜下观察肺组织的病理变化及测定肺泡损伤数（IQA）。结果与C组比较,IR组肺组织IQA显著升高，AI显著升高，Bcl-2基因和蛋白表达明显下降，Bax基因和蛋白表达明显上调，Bcl-2/Bax的比值降低（均P＜0.05），肺组织形态学发生异常改变；与IR组比较，EPO组、P组、SP组的IQA显著降低，AI显著降低，Bcl-2基因和蛋白表达上调，Bax基因和蛋白和表达下降，Bcl-2/Bax的比值增高（均P＜0.05），肺组织形态学结构异常改变有所减轻；与EPO组比较，SP组的IQA降低，AI显著降低，Bcl-2基因和蛋白表达上调，Bax基因和蛋白表达下降，Bcl-2/Bax的比值增高（均P＜0.05），SP组的肺组织形态学结构损伤较EPO组减轻。结论EPO后处理能减轻LIRI，其机制可能通过抑制JNK信号转导通路的激活，上调凋亡抑制因子Bcl-2的表达，下调促凋亡基因Bax的表达，提高Bcl-2/Bax比值，使肺组织细胞凋亡减少，改善其结构。 |
| 关键词: 促红细胞生成素 后处理 再灌注损伤 肺 细胞凋亡 |
| DOI： |
| 分类号: |
| 基金项目:浙江省中医药重点学科建设计划项目；温州市科技计划项目 |
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| Erythropoietin postconditioning attenuates pneumocyte apoptosis after lung ischemia/reperfusion in rats |
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Jin Xiaosheng,Xu Xianrong,Li Guoping,Jin Qian,Chen Haie,Shao Meiqin
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Tongde Hospital of Zhejiang province
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| Abstract: |
| Objective To investigate the effects of erythropoietin (EPO) postconditioning on pneumocyte apoptosis in lung ischemia/reperfusion injury (LIRI) of rats and its mechanisms. Methods Adult male Sprague-Dawley rats were randomly divided into 5 groups (n=8 in each group): control group (C), Lung ischemia/reperfusion group (IR), EPO+IR group (EPO), EPO+solvent control group (P), EPO+SP600125 group (SP). At the end of experiments the animals were sacrificed and lung samples were collected. The apoptosis index (AI) of pneumocytes was measured by terminal deoxynucleotidyl transferase mediated dUTP nick end abeling (TUNEL) method; the expressions of Bcl-2 and Bax mRNA and proteins were measured by RT-PCR and quantitative immunohistochemistry, respectively. The pathological changes of lung tissue were observed under light microscope and the index of quantitative assessment (IQA) of histological lung injury was counted. Results Compared withC group, IQA and AI in IR group
were increased, the expression of Bcl-2 was decreased, the expression of Bax was increased and Bcl-2/Bax was decreased (P＜
0.05); there were abnormal morphological changes under the light microscope. Compared with IR group, IQA and AI were decreased in EPO, P and SP groups, the expression of Bcl-2 was increased, Bax was decreased and Bcl-2/Bax was increased (P＜0.05); the morphological changes markedly reversed in EPO, P and SP groups. There were no significant differences in all indexes between P and EPO groups (P ＞0.05). Compared with EPO group, IQA and AI of SP group were decreased, the expression of Bcl-2 was increased, Bax was decreased and Bcl-2/Bax was increased (P＜0.05); the abnormal morphological changes in SP group were milder than those in EPO group. Conclusion Erythropoietin postconditioning may attenuate pneumocyte apoptosis in lung ischemic/reperfusion injury by inhibiting activation of JNK signal transduction pathway, and
up-regulating Bcl-2 expression and down-regulating Bax expression. |
| Key words: Erythropoietin Postconditioning Reperfusion injury Lung Apoptosis |
