Circ Cardiovasc Imaging:吸烟诱导老年性黄斑变性的罪魁祸首—可替宁

2017-06-12 fengxiangxin MedSci原创

吸烟是老年性黄斑变性(AMD)的主要危险因素之一,AMD的主要病理改变为视网膜色素上皮(RPE)细胞的进行性变性。尼古丁是香烟烟雾中主要的生物活性成分,可替宁是尼古丁在人体内进行初级代谢后的主要产物--烟草中的尼古丁在体内经细胞色素氧化酶2A6(CYP2A6)代谢后的产物,主要存在于血液中,随着代谢过程从尿液排出。具有半衰期长,在体液和组织细胞中浓度较高的特点。

吸烟是老年性黄斑变性(AMD)的主要危险因素之一,AMD的主要病理改变为视网膜色素上皮(RPE)细胞的进行性变性。尼古丁是香烟烟雾中主要的生物活性成分,可替宁是尼古丁在人体内进行初级代谢后的主要产物--烟草中的尼古丁在体内经细胞色素氧化酶2A6(CYP2A6)代谢后的产物,主要存在于血液中,随着代谢过程从尿液排出。具有半衰期长,在体液和组织细胞中浓度较高的特点。

假设可替宁的持续暴露对人RPE细胞的影响比尼古丁暴露更大。用尼古丁和(或)可替宁(1-2μM)连续处理人RPE细胞(ARPE-19)7天。RPE细胞经2μM可替宁以及尼古丁-可替宁混合物处理后MTT信号较低,而细胞凋亡或细胞完整性没有明显变化。此外,RPE细胞迁移率在可替宁持续暴露下降低,但在尼古丁持续暴露下没有发生变化。尼古丁和可替宁处理均减弱了RPE细胞的吞噬活性。

此外,可替宁以及尼古丁-可替宁混合物抑制了VEGF和IL-8的表达,并上调了TIMP-2的表达。可替宁处理之后,自噬基因的表达上调,而上皮间质转化标志物的表达下调。

总之,这项研究首次阐明,是可替宁导致体外培养的RPE细胞特性受到影响,而不是尼古丁。这可以解释吸烟诱导的视网膜色素上皮细胞的病理改变。

原始出处:

Zhang, X.Y. and T.K. Ng, Disruption of retinal pigment epithelial cell properties under the exposure of cotinine. 2017 Jun 9;7(1):3139. doi: 10.1038/s41598-017-03283-x.

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    2018-04-06 quxin068
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    2017-06-14 huangdf
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    2017-06-14 muzishouyi

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