抑制Notch信号对血小板源衍生生长因子诱导的肺血管重构的影响  

The Influence of Inhibiting Notch Signal on Pulmonary Vascular Remodeling Induced by PDGF

作　　者：乔莉娜[1] 王献民 刘忠强[1] 王晓琴[1] 周同甫[1] 华益民[1] 刘瀚旻[1] 

机构地区：[1]四川大学华西第二医院儿科,成都610041 [2]成都市妇女儿童中心医院心脏科,成都610000

出　　处：《四川大学学报（医学版）》2011年第6期766-770,共5页Journal of Sichuan University(Medical Sciences)

基　　金：国家自然科学基金(批准号30700913)资助

摘　　要：目的探讨抑制Notch信号对血小板源衍生生长因子(PDGF)诱导的肺血管重构的影响。方法用PDGF持续刺激培养的肺动脉血管条7d,观察γ-分泌酶抑制剂DAPT抑制Notch信号后,血管条Notch 1～4受体和其下游转录因子HERP1、2mRNA水平,以及血管条管壁厚度、血管壁细胞增殖细胞核抗原(PCNA)阳性率和caspase-3阳性率的改变。结果 PDGF持续刺激血管条7d,血管壁厚度增加近50%(P<0.05),伴有血管壁细胞PCNA阳性率升高(P<0.05)和caspase-3阳性率降低(P<0.05)。加入DAPT抑制Notch信号后,血管条Notch1～4受体mRNA水平无明显改变,但HERP1、2mRNA水平降低(P<0.05),而PDGF诱导的管壁厚度、PCNA和caspase-3阳性率的改变程度受抑制(P<0.05)。结论抑制Notch信号能抑制PDGF诱导的肺血管重构,干预Notch信号可能成为肺动脉高压治疗的一个新思路。Objective To explore the influence of inhibiting Notch signal on pulmonary vascular remodeling induced by PDGF.Methods Vessel strips taken from healthy Wistar rats were cultured together with extrogenous PDGF,the potent smooth muscle cell proliferation stimulators,for 7 days.Some vessel strips were cultured with PDGF and γ-secretase inhibitor DAPT,a Notch signaling inhibitor for 7 days.Vascular wall thickness,PCNA and caspase-3 positive cell rate were examined in vessel strips.The alterations of Notch 1 to 4 receptor and HERP1,2 mRNA were discerned by FQ-PCR to observe the influence of DAPT on Notch signal.At the same time,above indexes,which were related with pulmonary vascular remodeling,were measured too.Results PDGF stimulation in the cultured normal pulmonary arteries resulted in vascular medial thickness increase for about 50%,accompanied by significant increase in PCNA positive cell rate and decrease of caspase-3 positive cell rate.When DAPT were added to inhibit Notch signaling,the expression of HERP1,2 mRNA decreased,the degrees of PDGF induced vascular medial thickness and PCNA positive cell rate increase as well as caspase-3 positive cell rate decrease were all attenuated notably.Conclusion Inhibiting Notch signal induced by γ-secretase inhibitor lead to the suppression of pulmonary vascular remodeling induced by PDGF,suggesting inhibition of Notch signal pathway might be a novel strategy in the intervention of pulmonary hypertension.

关 键 词：NOTCH信号 血小板源衍生生长因子 肺 血管重构 

分 类 号：R363[医药卫生—病理学]