摘要
目的探讨低氧对妊娠SD大鼠维生素D代谢的影响及可能机制。方法选择成年SD雌性大鼠20只,将其分为常氧组(Normoxia组,8只)和低氧组(Hypoxia组,12只),按雌雄比例2∶1将10只成年SD雄性大鼠分配到以上两组,与雌鼠合笼饲养建立妊娠动物模型。应用ELISA法检测雌鼠血清维生素D水平;采用Real-time qPCR技术分析与肝、肾、胎盘维生素D代谢相关基因的表达情况;通过常规染色和免疫组织化学技术对胎盘进行形态学观察、分析。结果Normoxia组血清维生素D代谢活性物25(OH)2D3含量低于Hypoxia组,差异有统计学意义(P<0.05),即Hypoxia组代谢水平加快;Real-time qPCR结果显示,在低氧条件下,肝的CYP2R1基因表达量上调(P<0.05),肾的CYP27B1基因表达量上调(P<0.05),肾的CYP24A1基因表达量下调(P<0.05),胎盘的CYP2R1、CYP27B1基因表达量在两组无明显差异(P>0.05);胎盘的免疫组织化学结果显示,与Normoxia组相比,Hypoxia组CYP2R1、CYP27B1蛋白在胎盘的表达增加(P<0.05),而CYP24A1蛋白表达下降(P<0.05),且三种蛋白主要在胎盘滋养层细胞中表达;从胎盘染色切片的结果可知,Normoxia组和Hypoxia组在胎盘的形态上无明显改变。结论低氧可加快妊娠母体维生素D的代谢,其机制可能是由于低氧增加肝、肾、胎盘维生素D的代谢,同时破坏CYP24A1介导的维生素D负反馈机制;胎盘滋养层细胞中存在维生素D代谢系统和自分泌调节系统,且滋养层细胞可能是妊娠母体1,25(OH)2D3的来源。
Objective To investigate the effects and potential mechanism of hypoxia on vitamin D metabolism in pregnant SD rats.Methods Twenty adult female SD rats were divided into two groups∶normoxia group(8 rats)and hypoxia group(12 rats).Ten adult male SD rats were housed together with the above two groups of female rats in a 2∶1 ratio to establish a pregnancy model.The metabolic level of serum vitamin D in female rats was detected by ELISA.Real-time qPCR was used to analyze the expression of vitamin D metabolism-related genes in the liver,kidney and placenta.The morphology of placenta was observed and analyzed by HE staining and immunohistochemical sections.Results The content of serum vitamin D metabolic active substance 25(OH)2D3in normoxia group was lower than that in hypoxia group,and the difference was statistically significant(P<0.05).The metabolic level of hypoxia group was increased.Real-time qPCR results showed that under hypoxic conditions,the expression of CYP2R1 in the liver was up-regulated(P<0.05),the expression of CYP27B1 in the kidney was up-regulated(P<0.05),and the expression of CYP24A1 in the kidney was down-regulated(P<0.05).There was no significant difference in CYP2R1 and CYP27B1 in placenta between the two groups(P>0.05).The results of immunohistochemistry of placenta showed that the expression of CYP2R1 and CYP27B1 in placenta was increased in hypoxia group compared with normoxia group(P<0.05),while the expression of CYP24A1 decreased(P<0.05).The three proteins were mainly expressed in placental trophoblast cells.Form the results of placental HE staining sections,it can be seen that there was no significant variation in the morphology of placenta in normoxia group and hypoxia group.Conclusions Hypoxia can accelerate the metabolism of vitamin D in pregnant rats.The mechanism may be that hypoxia increases the metabolism of vitamin D in the liver,kidney and placenta,while destroys the negative feedback mechanism of vitamin D mediated by CYP24A1.There are vitamin D metabolic system and autocrine
作者
王雪妮
陈文静
李丹
李建华
WANG Xueni;CHEN Wenjing;LI Dan;LI Jianhua(Qinghai University,Xining 810016,China)
出处
《中国高原医学与生物学杂志》
CAS
2024年第2期90-97,共8页
Journal of Chinese High Altitude Medicine & Biology
