妊娠期高血压疾病大鼠PLGF、FABP4及与胎盘脂代谢的关系miRNA-181a

Relationship between PLGF,FABP4 and miRNA-181a and placental lipid metabolism in rats with hypertension disorder complicating pregnancy

目的探究妊娠期高血压疾病(HDCP)模型大鼠胎盘生长因子(PLGF)、脂肪酸结合蛋白4(FABP4)及miR-181a的表达情况及与胎盘脂代谢的关系。方法选取40只SPF级雌性SD大鼠,随机分成研究组(n=20)和对照组(n=20),研究组大鼠给予一氧化氮合酶抑制剂(L-NAME)50 mg/(kg·d)建立HDCP模型,对照组给予注射等剂量生理盐水。分别检测两组大鼠妊娠第10、15和20天的血压和24 h尿蛋白;所有大鼠在妊娠第21天终止妊娠,取出胎鼠记录胎鼠重量,取胎盘组织行HE染色观察胎盘组织形态变化,并检测脂代谢指标[游离脂肪酸(FFA)、游离胆固醇(FC)、甘油三酯(TG)、总胆固醇(TC)和胆固醇酯(CE)]水平;采用qRT-PCR法检测雌鼠胎盘组织PLGF、FABP4及miR-181a表达,分析PLGF、FABP4及miR-181a表达与各胎盘脂代谢指标的相关性。结果 HE染色结果显示,研究组胎盘绒毛数目明显减少,大部分绒毛不成熟,结构萎缩不清,空泡大,细胞浆疏松淡然,细胞核明显加深,细胞体积明显增大。妊娠第10天,两组大鼠收缩压和24 h尿蛋白水平比较差异无统计学意义(P>0.05);妊娠第15天和妊娠第20天研究组大鼠收缩压和24 h尿蛋白均显著高于对照组,差异有统计学意义(P<0.05)。研究组胎鼠重量显著低于对照组,差异有统计学意义(P<0.05)。研究组大鼠胎盘FFA、FC、TG、TC及CE水平均显著高于对照组,差异有统计学意义(P<0.05)。研究组PLGF水平显著低于对照组,FABP4及miR-181a水平显著高于对照组,差异有统计学意义(P<0.05)。相关性分析结果显示,PLGF与TG、TC存在明显负相关性(r=-0.473、-0.512,P<0.05),FABP4及miR-181a与TG、TC存在明显正相关性(P<0.05)。结论 PLGF、FABP4及miRNA-181a的异常表达在妊娠高血压疾病的发生与发展中存在明显作用,PLGF、FABP4及miRNA-181a可影响脂代谢,进而影响妊娠高血压疾病的发展。

Objective To investigate the expression of placental growth factor(PLGF),fatty acid binding protein 4(FABP4) and miR-181 a in rat model of hypertension disorder complicating pregnancy(HDCP) and their relationship with placental lipid metabolism.Methods 40 SPF female SD rats were randomly divided into study group and control group.Rats in the study group were given a nitric oxide synthase inhibitor(L-NAME) at 50 mg/(kg·d) to establish the HDCP model,and the control group was given equal injections of normal saline.Blood pressure and 24 h urinary protein were measured on the 10 th,15 th,and 20 th days of pregnancy in all 2 groups of rats.All rats terminated pregnancy on the 21 st day of pregnancy.The fetal rats were removed to record the weight of the fetus.The placental tissue was stained with HE to observe the placental tissue change and measure lipid metabolism indicators [free fatty acids(FFA),free cholesterol(FC),triglyceride(TG),total cholesterol(TC) and cholesterol ester(CE)] levels.qRT-PCR was used to detect the expression of PLGF,FABP4 and miR-181 a in placental tissues of female mice,and the correlations between the expression of PLGF,FABP4 and miR-181 a and each placenta lipid metabolism index were analyzed.Results The results of HE staining showed that the number of placental villi in the study group was significantly reduced,most of the villi were immature,the structure was atrophied,the vacuoles were large,the cytoplasm was loose,the nucleus was significantly deeper,and the cell volume was significantly increased.On the 10 th day of pregnancy,there was no significant difference in systolic blood pressure and 24 h urine protein between the two groups of rats(P>0.05).On the 15 th and 20 th day of pregnancy,the systolic blood pressure and 24 h urine protein of the study group were significantly higher than those of the control group(P<0.05).The fetal rat weight in the study group was significantly lower than that in the control group(P<0.05).The levels of placenta FFA,FC,TG,TC,and CE in the study group were significantly higher than those in the control group(P<0.05.).The PLGF level in the study group was significantly lower than that in the control group,and the levels of FABP4 and miR-181 a were significantly higher than those in the control group(P<0.05).The results of correlation analysis showed that PLGF had a significant negative correlation with TG and TC,and FABP4 and miR-181 a had a significant positive correlation with TG and TC.(P<0.05).Conclusions The abnormal expressions of PLGF,FABP4 and miRNA-181 a plaid a significant role in the pathogenesis and development of pregnancy-induced hypertension.PLGF,FABP4 and miRNA-181 a could affect lipid metabolism and then affect the development of pregnancy-induced hypertension.