目的观察经孕鼠尾静脉注射合体滋养细胞微粒(syncytiotrophoblast microparticles STBM)后,小鼠肾功能及肾脏病理改变。方法收集孕18 d C57小鼠的胎盘,制备小鼠合体滋养细胞微粒,利用电镜观察C57小鼠STBM的形态结构,BCA法测定C57小鼠STBM的蛋白水平;将C57孕鼠分为STBM组、对照组和PBS组,STBM组:自C57小鼠孕8 d起,每天以蛋白浓度为0.15 mg/m L的STBM(0.2 m L)经鼠尾静脉回输至小鼠体内,至孕18 d时收集小鼠24 h尿液测定尿微量蛋白(M-TP)、尿肌酐(U-Crea)、尿蛋白肌酐比(M-TP/Cr)、尿酸(U-Uric)、24 h尿蛋白(24 h U-TP),采集全血测定血清尿素氮(BUN)、肌酐(Scr)、胱抑素C(Cys-C),取肾脏标本切片后行HE染色观察肾组织结构变化;对照组:正常孕18 d小鼠收集尿液、采集全血、取肾脏进行检测;PBS组:自孕8 d起每天经鼠尾静脉注射PBS 0.2 m L,余处理同STBM组。结果 STBM组孕鼠尿液M-TP、M-TP/Cr、24 h U-TP明显高于对照组和PBS组(P〈0.01),与对照组比较,PBS组U-Uric未见明显变化(P〉0.05),而STBM组U-Uric显著降低(P〈0.01);STBM组血清BUN、Scr、Cys-C含量显著升高(P〈0.01);STBM组肾脏HE染色可见肾小球内皮细胞增生、肿胀、变形,肾小管云雾状变性。结论类子痫前期模型鼠有肾损伤,STBM可能在子痫前期肾损害中起重要作用。
Objective To determine the renal function and pathological changes after intravenous injection of syncytiotrophoblast microparticles( STBMs) in pregnant mice. Methods When the mice were pregnant for 18 d,the placentas were taken to prepare STBMs. The morphology of STBMs was observed by transmission electron microscopy,and the protein level of STBMs was detected with BCA Protein Assay Kit.Fluorescence-labeled STBMs were injected into the pregnant mice via the tail veins, and the in vivo distribution of STBMs were traced. The pregnant mice were divided into STBM group,control group and PBS group. The STBM group was treated by tail vein injection of STBMs( 0. 2 m L) with protein concentration of0. 15 mg / m L from the 8th day of the pregnancy. When the pregnancy lasted for 18 d,24-h urine of the mice was collected to detect microalbuminuria( M-TP),urine creatinine( U-Crea),urinary protein creatinine ratio( M-TP/Cr),24-h urine protein( 24 h U-TP) and uric acid( U-Uric). Meanwhile,the blood was sampled to detect urea nitrogen( BUN),creatinine( Scr) and cystatin C( Cys-C),and the kidney specimens were treated by hematoxylin-eosin( HE) staining to observe renal pathological changes. Results The urine M-TP,M-TP / Cr,and 24 h U-TP of the STBM group were significantly higher than those of the control group and the PBS group( P 0. 01). There was no significant difference in U-Uric between the control group and the PBS group( P 0. 05),but the U-Uric level was significantly decreased in the STBM group( P 0. 01).The serum BUN,Scr,and Cys-C were significantly increased in the STBM group( P 0. 01). The HE staining results showed glomerular endothelial cell proliferation,swelling,deformity,and renal tubular cloudy degeneration in the STBM group. Conclusion STBM raising can cause renal damage in the pregnant mice,so STBM may play an important role in the renal damage of preeclampsia.