子痫前期宫内环境导致子代大鼠海马HPA轴相关基因表达改变

Preeclampsia alters the expression of HPA axis related genes in the hippocampus of offspring rats

目的研究子痫前期宫内环境对子代SD大鼠海马下丘脑-垂体-肾上腺(hypothalamic-pituitaryadrenal,HPA)轴相关基因表达的影响。方法通过给妊娠第14天SD大鼠连续皮下注射亚硝基左旋精氨酸甲酯(L-NAME)至分娩的方法建立子痫前期大鼠动物模型,对照组予生理盐水1 mL皮下注射。用酶联免疫检测(ELISA)方法检测新生子代大鼠血皮质酮(corticosterone,CORT)浓度。用Real-time PCR方法和Western bolt分别检测8周龄子代大鼠海马组织糖皮质激素受体(glucocorticoid receptor,GR)、促肾上腺皮质激素释放激素(corticotropin releasing hormone,CRH)、CRH受体1(CRH receptor 1,CRHR1)和IL-6的mRNA水平及其蛋白质水平。结果与正常子代新生鼠相比,子痫前期子代新生鼠血CORT浓度升高(P<0.05)。与正常子代鼠相比,子痫前期青少年子代鼠海马GR、CRH和CRHR1 mRNA和蛋白质水平均增加(P<0.05),炎性因子IL-6mRNA和蛋白质水平均增加(P<0.05)。结论子痫前期宫内环境影响子代大鼠海马HPA轴相关基因的表达,在子代学习记忆能力受损中起作用。

Objective To explore the effect of preeclampsia on the expression of hypothalamic-pituitary-adrenal （HPA） axis related genes in the hippocampus of adolescent offspring rats. Methods The pregnant Sprague-Dawley rats were randomly divided into two groups to be given 125 mg·kg-1·d-1 L-NAME or 1 mL pure saline by daily injection from day 14 to delivery. Serum corticosterone （CORT） levels in neonatal offspring rats were detected by ELISA. The mRNA and protein levels of glucocorticoid receptor （GR）, corticotropin releasing hormone （CRH）, CRH receptor 1 （CRHR1） and IL-6 in the hippocampus of 8-week offspring rats were determined by real-time PCR and Western blot, respectively. Results Compared with normal neonatal rats, the serum CORT concentration of neonatal rats with preeclampsia was increased （P〈0.05）. Compared with normal adolescent offspring, the levels of GR,CRH and CRHR1 mRNA and protein were increased in the hippocampus of adolescent rats with preeclampsia （P〈0.05）, accompanied by increased IL-6 mRNA and protein （P〈0.05）, as a downstream inflammatory gene of the GR. Conclusions We found that adolescent SD rats exposed to preeclampsia showed alteration in the expression of HPA related genes in the hippocampus, which played a role in the impairment of learning and memory in children.