肿瘤坏死因子-α、可溶性血管内皮生长因子受体-1在妊娠期高血压疾病大鼠血清及胎盘中的表达水平及意义

Expression levels and significance of tumor necrosis factor-αand soluble vascular endothelial growth factor receptor-1 in serum and placenta of rats with hypertensive disorders complicating pregnancy

目的:探讨肿瘤坏死因子-α(TNF-α)、可溶性血管内皮生长因子受体-1(sFlt-1)在妊娠期高血压疾病(HDCP)大鼠血清及胎盘中的表达水平及意义。方法:选择20只孕鼠,随机分为HDCP组和对照组,每组各10只,HDCP组于妊娠14 d时,皮下注射L-精氨酸甲酯,连续7 d,建立HDCP大鼠模型,对照组皮下注射等体积0.9%氯化钠溶液。妊娠21 d时,比较各组大鼠血压、24 h尿蛋白含量,记录胎盘重量、胎鼠重量、胎鼠身长,苏木精伊红(HE)染色观察各组胎盘组织结构,原位末端标记技术(Tunel)检测胎盘组织细胞凋亡情况,蛋白质免疫印迹(WB)法检测胎盘组织TNF-α、sFlt-1蛋白表达水平。结果:HDCP组胎鼠重量、胎盘重量、胎鼠身长低于对照组(均P<0.05)。HDCP组大鼠妊娠21 d血压及尿蛋白含量高于妊娠14 d,HDCP组大鼠妊娠14、21 d血糖及尿蛋白含量高于对照组(均P<0.05)。HDCP组大鼠血清TNF-α、sFlt-1水平高于对照组(均P<0.05)。对照组大鼠胎盘组织形态和结构正常,细胞完整。HDCP组大鼠胎盘组织细胞结构不完整,绒毛数目减少,且绒毛大部分不成熟。对照组胎盘组织凋亡细胞较少,HDCP组胎盘组织细胞凋亡率高于对照组(均P<0.05)。HDCP组大鼠胎盘组织中TNF-α、sFlt-1蛋白表达高于对照组(均P<0.05)。结论:TNF-α、sFlt-1高表达可能与妊娠期高血压疾病发生密切相关。

Objective:To investigate the expression levels and significance of tumor necrosis factor-α(TNF-α)and soluble vascular endothelial growth factor receptor-1(sFlt-1)in serum and placenta of rats with hypertensive disorders complicating pregnancy(HDCP).Methods:A total of 20 pregnant rats were randomly divided into HDCP group and control group,with 10 rats in each group.The HDCP group was subcutaneously injected with L-arginine methyl ester on day 14 of pregnancy for 7 consecutive days to establish the HDCP model,and the control group was subcutaneously injected with the same volume of 0.9%sodium chloride solution.At 21 days of gestation,the blood pressure of rats in each group was compared for 24-hour urinary protein content,the weight of placenta,the weight of fetal rats and the body length of fetal rats were recorded.The structure of placenta tissue was observed by HE staining,and the apoptosis of placenta cells was detected by TUNEL,and the expression of TNF-αand sFlt-1 proteins in placenta tissues was detected by Western blot.Results:The weight,placental weight and body length of fetal rats in the HDCP group were lower than those in the control group(all P<0.05).The contents of blood pressure,urinary protein in HDCP group at 21 day of gestation were higher than those at 14 day of gestation,and the contents of blood glucose and urinary protein in HDCP group at 14 and 21 day of gestation were higher than those in control group(all P<0.05).The serum levels of TNF-αand sFlt-1 in HDCP group were higher than those in control group(all P<0.05).In the control group,the tissue morphology and structure of rat placenta were normal and the cells were intact.In the HDCP group,the structure of placental tissue was incomplete,the number of villi was reduced,and most of the villi were immature.There were fewer placental apoptotic cells in the control group.The apoptosis rate of placental cells in the HDCP group was higher than that in the control group(P<0.05).The expressions of TNF-αand sFlt-1 protein in placental tissue of HDCP group were higher than those of control group(all P<0.05).Conclusion:The high expression of TNF-αand sFlt-1 may be closely related to the occurrence of hypertensive disorders complicating pregnancy.