探讨孕期脂代谢异常疾病高脂血症(HLP)的发病机制及可能的关键因子。

选择50只Wistar雌性大鼠和16 Wistar雄性大鼠进行适应性饲养7 d后，按照雌、雄比例为1∶1，于傍晚进行合笼，获取优先受孕成功的孕鼠40只为研究对象。采用随机数字表法，将其平均分为2组进行不同方式饲养，高脂组(n＝20，采用高脂饲料喂养)和对照组(n＝20，采用普通饲料喂养)。采用全自动生化仪检测2组孕鼠胎盘组织血清脂肪酸结合蛋白(FABP)-4及血脂指标，包括总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)、极低密度脂蛋白(VLDL)、动脉硬化指数T。测量2组孕鼠胎盘面积及称量胎盘重量，采用苏木精-伊红(HE)染色观察胎盘脂质沉积、滋养细胞浸润、螺旋动脉改变情况；实时荧光定量聚合酶链式反应(RT-PCR)检测胎盘组织FABP-4与脂滴相关蛋白(perilipin)A、B、C、D mRNA相对表达水平。实验过程对动物的处置符合动物伦理学要求。

①高脂组孕鼠的胎盘面积及胎盘重量均大于、高于对照组，2组分别比较，差异有统计学意义(t＝－4.44、－1.93，P＝0.043、0.018)。②高脂组孕鼠血清FABP-4、TC、TG水平均高于对照组，而HDL水平则低于对照组，组间比较，差异亦有统计学意义(t＝－11.06、－17.81、－15.28、2.48，P＝0.024、0.010、0.010、0.002)。③2组孕鼠血清FABP-4水平与血清TC、TG水平呈正相关关系(r＝0.827、0.818，P<0.001)，与HDL水平呈负相关关系(r＝－0.426，P＝0.006)。④胎盘组织HE染色结果示：对照组胎盘组织未见明显脂肪细胞浸润，血管结构完整，无炎症细胞入侵；高脂组孕鼠胎盘组织中细胞质及小动脉周围存在明显空泡状脂肪细胞浸润、血管内膜纤维性增厚、管腔狭窄及管壁纤维素样坏死，并可见脂质细胞和炎性细胞浸润。⑤RT-PCR结果显示，高脂组孕鼠胎盘组织中FABP-4与perilipin A、B、C mRNA相对表达水平，均较对照组显著降低，组间比较，差异均有统计学意义(t＝10.72、18.68、9.21、55.39，P＝0.009，0.001、0.001、<0.001)。

Wistar大鼠高脂饮食摄入，会下调胎盘组织相关脂蛋白表达，导致胎盘脂肪酸转运异常，进而出现胎盘脂质沉积、螺旋动脉改变，并引发炎症反应，导致胎盘功能或结构异常，最终导致母儿不良妊娠结局。FABP-4作为特殊的脂肪因子参与胎盘滋养细胞脂质代谢，可能作为评估胎盘功能的新手段。

To investigate changes and significance of fatty acid-binding protein (FABP)-4 in serum and placental tissues and related lipid protein expression of high-fat induced pregnant rats.

A total of 50 Wistar female rats and 16 Wistar male rats were combined in cages at night according to the ratio of female to male of 1∶1 after 7 days of adaptive feeding. After successful fertilization, 40 pregnant rats were selected and divided into high-fat group (n=20, high-fat diet) and control group (n=20, ordinary diet) by random number table method. Serum FABP-4 and blood lipid levels, including total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL), low density lipoprotein (LDL), very low density lipoprotein (VLDL) and arteriosclerosis index Twere measured by automatic biochemical analyzer between 2 groups. The placental area and weight were measured in pregnant rats. Placental lipid deposition, trophoblast infiltration, and spiral artery changes were observed by hematoxylin-eosin (HE) staining. The mRNA relative expression levels of FABP-4, lipid drop related protein(perilipin) A, B, C and D in placental tissues were determined by real time-quantitative polymerase chain reaction (RT-PCR). The disposal of animals during the experiments was in accordance with the requirements of animal ethics.

①The placenta weight and placenta area of high-fat group were higher than those in control group, and there were statistical differences (t=-4.44, -1.93; P=0.043, 0.018). ②The serum levels of FABP-4、TC、TG of pregnant rats in high-fat group were higher than those in control group, while serum level of HDL was lower, and the above differences were statistically significant (t=-11.06, -17.81, -15.28, 2.48; P=0.024, 0.010, 0.010, 0.002). ③The serum level of FABP-4 was positively correlated with serum TC and TG levels (r=0.827, 0.818; P<0.001) and negatively correlated with HDL level (r= 0.426, P=0.006). ④The results on placenta tissue by HE staining showed that there was no obvious adipocyte infiltration in the placental tissue of control group, the vascular structure was intact, and there was no inflammatory cell invasion. In the placental tissue of pregnant rats in the high-fat group, there were obvious vacuolar adipocytes infiltrating, the vascular intima fibrous thickened lumen stenosis and cellline-like necrosis of the tube wall around the cytoplasm and arterioles, and the infiltration of lipid and inflammatory cells were observed. ⑤RT-PCR results showed that the relative expression levels of FABP-4, perilipin A, B and C mRNA in placental tissues of high-fat group were significantly lower than those in control group, and the differences between 2 groups were statistically significant (t=10.72, 18.68, 9.21, 55.39; P=0.009, 0.001, 0.001, 0.001).

During pregnancy, high-fat intake in Wistar rats can down-regulate the expression of placenta-related lipoproteins, resulting in abnormal fatty acid transport in placenta and the placental lipid deposition, arterial changes, triggering inflammatory responses, abnormal placental function or structure, and ultimately leading to adverse perinatal outcomes; FABP-4, as a special adipokines, is involved in the lipid metabolism of placental trophoblast cells, and it may be used as a new means to evaluate placental function through its dynamic monitoring;