登革病毒对人血管内皮细胞分泌ET-1及PGI_2的影响

Effect of dengue virus infection on the production of ET 1 and PGI 2 by human vascular endothelial cells

目的 研究登革病毒感染对人血管内皮细胞分泌重要的血管活性物质ＥＴ１ 及ＰＧＩ２ 的影响，以了解登革出血热及登革休克综合征（ＤＨＦＤＳＳ）的发病机制。方法 用登革病毒Ⅱ型，感染人脐静脉内皮细胞（ＨＵＶＥＣ） ，于感染后４ 、２４ 、４８ 、７２ 及９６ 小时，分别收集病毒感染上清液，用放射免疫检测法测定ＥＴ１ 及ＰＧＩ２ 的含量。结果 登革病毒感染可使ＨＵＶＥＣ分泌ＥＴ１ 及ＰＧＩ２ 的能力受到明显抑制。在病毒感染早期（４ 小时），ＨＵＶＥＣ分泌ＥＴ１ 及ＰＧＩ２ 的能力即受到明显抑制。登革病毒对ＨＵＶＥＣ分泌ＥＴ１ 抑制作用强烈而持久，至感染后９６ 小时，ＨＵＶＥＣ分泌ＥＴ１ 的能力与未受感染的阴性对照组比较，差异仍有显著性。然而，登革病毒对ＨＵＶＥＣ 分泌ＰＧＩ２ 的抑制作用，可随时间的推移而减弱，至感染后９６ 小时，ＨＵＶＥＣ分泌ＰＧＩ２ 的能力已达正常水平。结论 登革病毒感染可影响血管内皮细胞分泌血管活性物质ＥＴ１ 及ＰＧＩ２ 的功能，导致血管通透性增加和凝血、止血功能障碍。因此，登革病毒所致的血管内皮细胞功能障碍。

Objective To study the effect of dengue virus infection on the production of endothelin 1(ET 1) and prostacyclin 2(PGI 2) by human umbilical cord vein endothelial cells (HUVECs).Methods HUVECs were infected by dengue 2 virus (DV 2), the culture supernatants were collected at 4,24,48,72 and 96 hours postinfection, and the levels of ET 1 and PGI 2 were measured by radio immunoassay.Results The results showed that inhibition of production of ET 1 and PGI 2 was induced by dengue virus infection in HUVECs. Marked inhibition of ET 1 and PGI 2 production was observed as early as 4h postinfection and the inhibitory effect continued until 96h postinfection. Significant differences were shown between the ET 1 concentration of the virus infected and non infected cells. Nevertheless, the inhibitory effect of dengue virus infection on the production of PGI 2 gradually decreased and the PGI 2 concentration reverted to normal level at 96h postinfection. No significant difference between the PGI 2 concentration of the virus infected and non infected cells was seem.Conclusion The present study suggests that dengue virus infection of vascular endothelial cells could affect their normal functions of secretion of vasoactive substances, resulting in increased vascular permeability and impairment of homostasis and blood coagulation. Therefore, functional impairment of vascular endothelial cells induced by dengue virus might be an important aspect in the pathogenesis of DHF/DSS.