机构地区:[1]上海交通大学医学院实验动物科学部,上海200025 [2]上海市农业科学研究院畜牧兽医研究所,上海201106
出 处:《实验动物与比较医学》2023年第4期371-380,共10页Laboratory Animal and Comparative Medicine
基 金:上海市科学技术委员会科技创新行动计划“崇明白山羊先兆子痫及乳腺发育疾病模型的生物学特性评价”(19140900103);上海高校教师培养计划-实验技术队伍建设计划“周晶”。
摘 要:目的建立山羊先兆子痫动物模型,并收集该疾病模型各项生理指标和母体的生物学特性数据,与人类该疾病的发生发展特征相对照,为防治人类先兆子痫疾病的发生提供参考。方法将23头雌性崇明白山羊分为3组,其中对照组妊娠母羊临产期前不进行任何手术操作;假手术组在母羊妊娠(100±5)d时行先兆子痫假手术造模,仅暴露并游离其子宫体动脉;手术组于母羊妊娠(100±5)d时,在其一侧子宫体动脉上放置银质血管夹,夹闭动脉部分内径,制作先兆子痫模型。对妊娠100~140 d的对照组和手术组母羊连续监测其心率和后肢血压,并利用血流仪结合血流探头、动物生理信号采集仪采集假手术组母羊的子宫动脉侧支内血流数据,以及手术组母羊在放置血管夹前后子宫动脉侧支内的血流变化情况。在预期分娩日期前,取母羊颈静脉血进行血常规、肌酐、尿素氮和血液离子分析;同时采集各组母羊尿液,进行尿蛋白、尿肌酐分析。所有实验组均于母羊妊娠(140±5)d时行剖宫取胎术,然后取各组母羊的肝、肾、子宫和胎盘组织进行苏木精-伊红染色,以进行病理学观察。结果手术造模15 min后手术组母羊的子宫体动脉血流量保持稳定,血流流量差相对于对照组和假手术组均降低(P<0.05,P<0.01)。相较于对照组,手术组母羊在产前出现血清渗透压升高、血红蛋白降低、血糖和血清尿素氮值升高,以及钙、钠、氯离子含量增高等变化(均P<0.05),并出现蛋白尿,尿肌酐及尿蛋白肌酐比均明显高于对照组和假手术组(均P<0.05)。手术组动物的手术侧子宫体动脉弹力层较对侧增厚,但结构松散;手术侧胎盘出现细胞间质肿胀、炎性细胞浸润等病理变化。以上生理指标特征均与人类先兆子痫的临床指标较为一致。结论通过血流仪验证,以及妊娠后期母羊各项生理指标检测证明,本实验成功构建了山羊先兆子痫�Objective Establish an animal model of preeclampsia in goats,collect data on various physiological indicators and maternal biological characteristics of the disease model to compare with clinical feature of the disease in humans,provide reference for the prevention and treatment of preeclampsia in humans.Methods Twenty-three goats bred in Chongming district were divided into three groups:Control group,no surgical procedure was performed on animals of this group;sham group,ewes in this group underwent the sham operation on the 100±5th day of gestation,and only the uterine artery was exposed and dissociated;surgical group,a silver vascular clamp was clipped on one side of the uterine body artery of the ewe to narrow the inner diameter of the artery at the same gestation period(100±5)days.Heart rate and hindlimb blood pressure were continuously monitored in control and surgical ewes from 100 to 140 d of gestation,and blood flow data within the lateral branches of the uterine arteries of ewes in the sham group were collected using a hemodynamometer in combination with a hemodynamic probe and an animal physiological signal collector,as well as changes in blood flow within the uterine arteries in the lateral branches of the uterine arteries of the surgical group before and after placement of vascular clips in the surgical ewes.At the expected date of delivery,jugular vein blood was taken from ewes for routine blood test,creatinine,urea nitrogen,and blood ion analysis;urine was also collected from ewes in each group for analysis of urinary protein and urinary creatinine.All experimental groups were subjected to cesarean section on the 140±5th day of gestation in ewes,and then liver,kidney,uterus and placenta tissues were taken from ewes in each group and stained with HE for pathological observation.Results After 15 minutes of preeclampsia modeling surgery,blood flow volume remained stable in the vessel stenosis segment and the volume differential was relatively reduced in comparison to the control group and sham grou
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