Pulmonary apoptosis in aged and oxygen-tolerant rats exposed to hyperoxia
Pulmonary apoptosis in aged and oxygen-tolerant rats exposed to hyperoxia
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DOI：
10.1152/ajplung.1998.275.1.l14
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发表时间：
1998-07-01
影响因子：
4.9
通讯作者：
Choi, AMK
中科院分区：
文献类型：
--
作者：
Otterbein, LE;Chin, BY;Choi, AMK
越来越多的证据表明，遗传毒性和氧化应激可诱导培养细胞的程序性细胞死亡或凋亡。然而，很少有人知道是否氧化应激导致的有害影响，高氧可以诱导细胞凋亡在体内，甚至更少的是已知的功能意义的细胞凋亡在体内响应于高氧。使用高氧作为氧化剂诱导的大鼠肺损伤的模型，我们表明，高氧应激的结果在肺中的显着的凋亡信号。通过末端转移酶dUTP缺口末端标记分析，从暴露于高氧的大鼠获得的肺组织切片以时间依赖性方式表现出细胞凋亡增加。为了研究高氧诱导的肺细胞凋亡是否与肺损伤的程度或对高氧的耐受性（适应性）相关，我们用年龄依赖性高氧耐受性大鼠模型研究了细胞凋亡的模式。我们发现，细胞凋亡与老年大鼠高氧生存率增加，肺损伤水平降低，测定胸腔积液量，肺湿干重，髓过氧化物酶含量老年大鼠与年轻大鼠高氧后。我们还研究了这种关系的耐受性高氧的替代模型。脂多糖（LPS）处理的幼年大鼠不仅表现出对高氧的耐受性，而且在高氧后与盐水处理的大鼠相比，细胞凋亡指数显着降低。为了进一步分离衰老和耐受性的影响，我们表明，用LPS预处理的老年大鼠没有表现出对高氧的耐受性。此外，类似于高氧耐受LPS预处理的年轻大鼠，非耐受LPS预处理的老年大鼠也表现出显着降低的凋亡指数相比，老年大鼠暴露于高氧单独。总之，我们的数据表明，高氧诱导的细胞凋亡在体内可以调制的老化和耐受性的影响。我们的结论是，有没有整体之间的关系，细胞凋亡和耐受。
Accumulating evidence demonstrates that genotoxic and oxidant stress can induce programmed cell death or apoptosis in cultured cells. However, little is known about whether oxidative stress resulting from the deleterious effects of hyperoxia can induce apoptosis in vivo and even less is known regarding the functional significance of apoptosis in vivo in response to hyperoxia. Using hyperoxia as a model of oxidant-induced lung injury in the rat, we show that hyperoxic stress results in marked apoptotic signals in the lung. Lung tissue sections obtained from rats exposed to hyperoxia exhibit increased apoptosis in a time-dependent manner by terminal transferase dUTP nick end labeling assays. To examine whether hyperoxia-induced apoptosis in the lung correlated with the extent of lung injury or tolerance (adaptation) to hyperoxia, we investigated the pattern of apoptosis with a rat model of age-dependent tolerance to hyperoxia. We show that apoptosis is associated with increased survival of aged rats to hyperoxia and with decreased levels of lung injury as measured by the volume of pleural effusion, wet-to-dry lung weight, and myeloperoxidase content in aged rats compared with young rats after hyperoxia. We also examined this relationship in an alternate model of tolerance to hyperoxia. Lipopolysaccharide (LPS)treated young rats not only demonstrated tolerance to hyperoxia but also exhibited a significantly lower apoptotic index compared with saline-treated rats after hyperoxia. To further separate the effects of aging and tolerance, we show that aged rats pretreated with LPS did not exhibit a significant level of tolerance against hyperoxia. Furthermore, similar to the hyperoxia-tolerant LPS-pretreated young rats, the nontolerant LPS-pretreated aged rats also exhibited a significantly reduced apoptotic index compared with aged rats exposed to hyperoxia alone. Taken together, our data suggest that hyperoxia-induced apoptosis in vivo can be modulated by both aging and tolerance effects. We conclude that there is no overall relationship between apoptosis and tolerance.