脂肪细胞因子Visfatin在子痫前期发病中对炎性反应和血管内皮损伤的调控研究

PE is a pregnancy-specific syndrome characterized by maternal hypertension and proteinuria occurring after the 20th week of gestation. By far the etiology and pathogenesis of preeclampsia has not been well understood.Our preliminary data showed that the expression of serum visfatin was upregulated in preeclampsia compared with that in control group.In this project,we mainly aim to: 1)compare visfatin expression in placenta and serum between preeclampsia and normal pregnancy by ELISA and real time PCR,and evaluate the predictive values of visfatin for preeclampsia；2)study the effects of visfatin on trophoblast and endothelial vascular function by testing the ability of cell outgrowth,invasion, tube formation of HUVEC on Matrigel in vitro and the Matrigel plug assay in vivo；3)identify the interaction of visfatin with VEGF/Flt-1 angiogenic system by western blot,and to detect whether visfatin can regulate inflammatory factor such as TNF-α、IL-6 and CRP expression；4)to create the sFlt-1-induced -rat model of preeclampsia,and to evaluate whether visfatin contribute to preeclampsia by regulating VEGF/Flt-1 angiogenic system and inflammatory reaction；5)test the serum visfatin levels in women of preeclampsia after treatment,and observe the rate of placental abruption, HELLP syndrome,and fetal growth restricted to evaluate the prognostic effect of preeclampsia. This study may give new insight for the etiology and pathogenesis of preeclampsia, and to provide a new potential bio-marker for early prediction of risk for developing preeclampsia,and a novel therapeutic target for preeclampsia.

子痫前期是妊娠并发症之一，发病机理仍不清楚。预实验证实Visfatin在子痫前期患者血清中水平升高。本项目运用ELISA等技术检测Visfatin在子痫前期患者和正常孕妇胎盘、血清中的差异水平，ROC曲线评价子痫前期发生风险；通过滋养层细胞增殖、侵润实验，HUVEC管状结构形成及在体Matrigel栓子试验，研究Visfatin调控滋养层细胞和血管内皮损伤的作用；研究Visfatin对炎症反应和血管内皮损伤的相关因子的调节作用；建立过或沉默表达Visfatin的sFlt-1诱导的子痫前期大鼠模型，检测Visfatin与内皮损伤和炎症反应的相关性；检测经临床治疗后的子痫前期患者血清Visfatin水平，观察胎盘早剥率、HELLP综合征、胎儿发育迟缓等预后事件。本课题从细胞-分子-整体-临床等多层次来证明我们的假设，为子痫前期病因学研究提供新的数据，为子痫前期早期诊断、治疗提供新的指标和靶点。

子痫前期是妊娠并发症之一，发病机理仍不清楚。预实验证实Visfatin在子痫前期患者血清中水平升高。本项目运用ELISA等技术检测Visfatin在子痫前期患者和正常孕妇胎盘、血清中的差异水平，子痫前期患者胎盘中Visfatin的水平明显升高，其相对定量为正常对照组的2倍多，P<0.05；通过滋养层细胞增殖、侵润实验，HUVEC管状结构形成试验，研究Visfatin调控滋养层细胞和血管内皮损伤的作用，结果显示Visfatin可促进滋养层细胞侵润行为及促进内皮细胞管形成能力；研究Visfatin对炎症反应和血管内皮损伤的相关因子的调节作用，结果显示Visfatin可促进了IL-6 和TNF-α的表达，及促进VEGF/Flt-1系统的表达，并且均呈剂量依赖关系；建立过或沉默表达Visfatin的sFlt-1诱导的子痫前期大鼠模型，检测血压及生化指标，结果证实Visfatin与子痫前期发生发展存在一定相关性；检测经临床治疗后的子痫前期患者血清Visfatin水平，观察早产、胎盘早剥率、产后出血、HELLP综合征等妊娠结局事件，进一步证实了Visfatin与子痫前期的相关性。本研究从细胞-分子-整体-临床等多层次均证实了Visfatin与子痫前期发病过程的相关性，为子痫前期病因学研究提供新的数据，为子痫前期早期诊断、治疗提供新的可能指标和靶点。