摘要
目的探讨补体激活在应激后自发性流产孕鼠早期流产及宫内发育迟缓(intrauterine growth restriction)中的作用。方法将雌性CBA/J小鼠×雄性DBA/2J小鼠以2∶1合笼交配,建立自然流产模型。将所获得的CBA孕鼠随机分为3组:模型组、低应激组及高应激组,每组各19只;建立正常妊娠模型CBA/J(雌)×BALB/c(雄)孕鼠20只并设为对照组。然后,对实验组进行声波刺激,低应激组孕鼠于妊娠5.5 d给予持续24 h 460 Hz、88 dB,1 s/次,间隔14 s的声波刺激,高应激组于相同时间给予持续24 h 460 Hz、88 dB,5 s/次,间隔10 s声波刺激。对照组及模型组孕鼠均不接受任何声波刺激。观察、计算并比较各组小鼠胚胎吸收率、胚胎重量,检测各组血清补体C3a、血管内皮生长因子(VEGF)和可溶性血管内皮生长因子受体(sFlt-1)浓度及蜕膜VEGF的表达水平,分析这些分子与早期流产及IUGR的关系。结果模型组孕鼠胚胎吸收率、血清C3a、sFlt-1水平相比对照组明显升高(P<0.05),胚胎重量及血清VEGF水平、蜕膜组织VEGF表达水平显著低于对照组(P<0.05);相比模型组,应激组胚胎吸收率、血清C3a、sFlt-1水平显著升高(P<0.05),存活胚胎重量、血清VEGF水平及蜕膜组织VEGF表达显著下降(P<0.05),且程度均与其接受应激的强度呈正比(P<0.05)。结论应激诱导补体系统异常激活,且活化的程度与其受应激的强度成正比,异常活化的补体成分可能通过sFlt途径导致胎盘发育不足,引起早期流产及IUGR的发生。
Objective To investigate the role of complement activation in stress-induced early abortion and intrauterine growth restric- tion（IUGR） of experimental spontaneous abortion pregnant mice. Methods CBA/J female mice were mated with DBA/2J male mice by 2：1 to establish abortion-prone models, which were subdivided randomly into three groups （n = 19 in each group） ： model group, low stress group and high stress group. The non-abortion-prone （ CBA/J × BALB/c ） matings were used as blank control group （ n = 20 ）. Then the sonic stress was performed in experimental group. The pregnant mice in low stress group were consecutively given the stress of 24 h sonic stimulation of 460 Hz,88 dB,1 s with the interval of 14 s at pregnancy 5.5 d. The pregnant mice in high stress group were treated by the stress of 24 h stimulaiton of 460 Hz,88 dB,5 s with the interval of 10 s at pregnancy 5.5 d. Pregnant mice in control group and model group received no intervention. At the end of experiments, the fetal resorption frequency and embryo weight were ob- served and assessed,and the levels of complement C3a, vascular endothelial growth factor（VEGF） and soluble fms-like tyrosine ki- nase-1 （ sFlt-1 ） in serum and the expression of VEGF in deciduas were detected in all groups. The relationship between the levels of these indices and the early abortion, IUGR was analyzed. Results The fetal resorption frequency and serum concentrations of C3a and sFh-1 in model group were significantly higher than those in control group（ P 〈 O. 05 ）. The embryo weight, levels of serum VEGF and decidual VEGF in model group were significantly lower than those in control group（ P 〈 0. 05 ）. Compared with model group, the fe- tal resorption frequency and concentrations of C3a and sFh-1 in serum were significantly increased in stress groups（P 〈0. 05 ）, while the embryo weight and levels of VEGF were significantly decreased in stress groups （ P 〈 0. 05 ）. The variability of these factors was positively related to the intensity of stress. Conclusion Sonic stress could induce the excessive activation of complement system, and the degree of activation is positively related to the stress intensity. The abnormal activation of complement components might result in the development deficiency of placenta through sFh pathway, and then cause the early spontaneous abortion and IUGR.
出处
《山西医科大学学报》
CAS
2014年第10期929-933,1001,1002,共7页
Journal of Shanxi Medical University
基金
西安交通大学第二附属医院科研基金资助项目(YJ(QN)201116)
关键词
补体激活
应激
自然流产
宫内发育迟缓
sFlt途径
complement activation
stress
spontaneous abortion
intrauterine growth restriction
sFlt pathway
