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慢性间歇低氧是指长时间反复低氧、复氧交替过程,其可对机体多个系统造成损害[1-3]。近几年通过大量动物实验发现,慢性间歇低氧可造成大鼠肺组织损伤。内质网应激是指当机体遭受钙超载、氧自由基侵袭、能量耗竭等外界刺激时,内质网功能紊乱导致大量未折叠或错误折叠蛋白在内质网腔内堆积及Ca2+平衡紊乱的状态[4-5], CHOP是内质网应激的标志性蛋白[6-8],介导细胞凋亡、参与多种疾病的发生、发展。但CHOP在慢性间歇低氧大鼠肺组织中的表达水平变化研究甚少。本研究通过建立慢性间歇低氧大鼠模型,采用HE染色法观察慢性间歇低氧大鼠肺组织病理形态变化,采用免疫组织化学(免疫组化)法检测大鼠肺组织中CHOP蛋白,探讨CHOP在慢性间歇低氧大鼠肺组织中表达水平变化。
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CIH组大鼠肺泡结构破坏,肺泡壁间隔增宽,可见间质水肿,少量炎性细胞浸润,部分肺泡融合;UC组肺组织未见明显病理形态改变(见图 1)。
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光学显微镜下观察CHOP蛋白阳性细胞细胞质呈棕黄色, 阳性细胞的表达主要集中于肺泡上皮细胞。CIH组大鼠肺组织CHOP蛋白表达较UC组明显增多,且随低氧时间延长,CHOP表达呈逐渐增多趋势(P < 0.01)(见图 2、表 1)。
分组 n 1周 2周 3周 4周 F P MS组内 UC组 6 10.47±0.40 10.59±0.50 10.57±0.48 10.48±0.42 0.11 >0.05 0.201 CIH组 6 36.12±4.46 48.18±6.23** 64.16±5.09**## 72.12±5.78**##▲ 52.86 < 0.01 29.505 t — 14.03 14.73 25.68 26.05 — — — P — < 0.01 < 0.01 < 0.01 < 0.01 — — — q检验:与1周比较** P < 0.01;与2周比较## P < 0.01;与3周比较▲ P < 0.05 表 1 2组大鼠肺组织CHOP蛋白吸光度值比较(x±s)
CHOP在慢性间歇低氧大鼠肺组织表达水平变化
Change of CHOP expression level in lung tissue of chronic intermittent hypoxia rats
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摘要:
目的建立慢性间歇低氧大鼠模型,探讨内质网应激标志蛋白CHOP在慢性间歇低氧大鼠肺组织表达水平变化。 方法选取Wistar雄性大鼠48只随机分成慢性间歇低氧组(CIH组)和对照组(UC组),每组各自分成4个时间亚组,分别为自实验之日起1周、2周、3周、4周,每个时间亚组6只大鼠。采用HE染色法及免疫组织化学法,观察比较CIH组与UC组大鼠肺组织病理形态变化及CHOP蛋白的表达变化。 结果CIH组大鼠肺泡结构破坏,肺泡壁间隔增宽,可见间质水肿,少量炎性细胞浸润,部分肺泡融合;UC组肺组织未见明显病理形态改变。免疫组织化学法检测结果提示,CHOP蛋白的表达主要集中于肺泡上皮细胞,CIH组大鼠肺组织CHOP蛋白表达较UC组明显增多,且随低氧时间延长,CHOP表达呈逐渐增多趋势(P < 0.01)。 结论CHOP在慢性间歇低氧大鼠肺组织中表达水平升高。 Abstract:ObjectiveTo establish the rat model of chronic intermittent hypoxia, and detect the expression level of endoplasmic reticulum stress marker protein CHOP in lung tissue of chronic intermittent hypoxia rats. MethodsForty-eight male Wistar rats were randomly divided into the chronic intermittent hypoxic(CIH) group and control(UC) group.Each group was subdivided into 4 subgroups, including 1 week, 2 weeks, 3 weeks and 4 weeks subgreups(6 rats in eech subgroup).The histopathological changes of lung tissue and expression level of CHOP protein in CIH group and UC group were analyzed using HE staining and immunohistochemistry. ResultsIn CIH group, the alveolar structure was destroyed, the alveolar wall septum widened, the interstitial edema was seen, a small amount of inflammatory cells infiltrated, and the partial alveolar fused.No obvious pathological change was found in the UC group.The results of immunohistochemistry showed that the expression level of CHOP protein in CIH group rats was significantly higher than that in UC group, and the CHOP expression increased with the duration of hypoxia(P < 0.01). ConclusionsThe expression of CHOP in lung tissue of chronic intermittent hypoxia rats increases. -
Key words:
- chronic intermittent hypoxia /
- endoplasmic reticulum stress /
- CHOP /
- lung tissue
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表 1 2组大鼠肺组织CHOP蛋白吸光度值比较(x±s)
分组 n 1周 2周 3周 4周 F P MS组内 UC组 6 10.47±0.40 10.59±0.50 10.57±0.48 10.48±0.42 0.11 >0.05 0.201 CIH组 6 36.12±4.46 48.18±6.23** 64.16±5.09**## 72.12±5.78**##▲ 52.86 < 0.01 29.505 t — 14.03 14.73 25.68 26.05 — — — P — < 0.01 < 0.01 < 0.01 < 0.01 — — — q检验:与1周比较** P < 0.01;与2周比较## P < 0.01;与3周比较▲ P < 0.05 -
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