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机构地区:[1]上海交通大学医学院附属瑞金医院心脏科,上海20025 [2]武警上海总队医院妇产科,上海201103 [3]上海生命科学研究院营养科学研究所食品安全重点实验室,上海200031
出 处:《诊断学理论与实践》2014年第3期312-315,共4页Journal of Diagnostics Concepts & Practice
基 金:上海市科委自然基金面上项目(13ZR1425700)
摘 要:目的:探讨前列腺素受体家族在低氧诱导的肺动脉高压平滑肌细胞中的表达变化。方法:体内实验,以低氧(10%O2)3周诱导建立小鼠肺动脉高压模型,分离肺动脉;体外实验,分别对小鼠源性和人源性的肺动脉平滑肌细胞进行低氧(1%O2)24 h的诱导。提取相应组织或细胞的RNA,以反转录-聚合酶链反应(RT-PCR)扩增不同前列腺素受体基因片段,并将产物进行琼脂糖凝胶电泳。结果:无论是小鼠源性还是人源性的肺动脉平滑肌细胞中,前列腺素受体基因基础表达值均以血栓素A2受体TP和前列腺素E受体1(E-prostanoid receptor 1,EP1)为最高,EP2、EP3、EP4和前列腺素I2受体(IP)居中,前列腺素D1受体、前列腺素D2受体和前列腺素F2α受体最少。在低氧诱导后,小鼠肺动脉平滑肌细胞血栓素A2受体基因和EP3受体基因表达上调显著,而前列腺素D1受体、EP1和前列腺素I2受体则明显下调。结论:在低氧诱导下,前列腺素受体基因表达发生不同变化,对筛选不同前列腺素用于肺动脉高压的疗效研究和新药开发及探究其病理机制有重要意义。Objective: To investigate the changes of expression of prostaglandin receptors in pulmonary artery smooth muscle cells when treated with or without hypoxic stimulus. Methods: In vivo, pulmonary artery was isolated from mice treated with three-week hypoxia (10% 02). In vitro, mice or human derived pulmonary artery smooth muscle cells were subjected to 1% 02 for 24 hours. Total RNA from tissue homogenates and cell lysates were extracted and were then amplified into different gene products of prostaglandin receptors by RT-PCR. Quantitative PCR products were confirmed by a single band of expected size on agarose gel. Results: TP and EP1 showed the highest basal expression in human as well as in mice pulmonary artery smooth muscle cells, EP2, EP3, EP4 and IP showed moderate expression, and DP1, DP2 and FP showed the lowest expression. RNA that encoded the TP and EP3 receptor was significantly increased in response to hypoxia. In contrast, DP1, EP1 and IP receptors were significantly down-regulated. Conclusions: Levels of some of the prostaglandin receptors change in response to hypoxia, which might have important meaning for screening different prostaglandins for the study of pathophysiologic mechanism and its efficacy on pulmonary hypertension and the development of new drugs.
分 类 号:R541.9[医药卫生—心血管疾病]
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