实验动物与比较医学 ›› 2023, Vol. 43 ›› Issue (4): 371-380.DOI: 10.12300/j.issn.1674-5817.2023.036

• 华东会议优秀论文展 • 上一篇    下一篇

山羊先兆子痫疾病模型的构建及母体生物学特性评价

卢今1(), 王剑1, 朱莲1, 严国锋1, 马政文1, 李垚1, 戴建军2, 朱寅秋1, 周晶1()()   

  1. 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
  • 收稿日期:2023-03-21 修回日期:2023-06-06 出版日期:2023-08-25 发布日期:2023-09-14
  • 通讯作者: 周 晶(1985—),女,生物工程硕士,实验师,研究方向:实验动物医学。E-mail:zj2008@shsmu.edu.cn。ORCID:0009-0005-2626-1561
  • 作者简介:卢 今(1990—),女,兽医学硕士,实验师,研究方向:实验动物医学。E-mail:ashleelu@shsmu.edu.cn
  • 基金资助:
    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”

Establishment of Preeclampsia Model in Goat and Evaluation on Maternal Biological Characteristics

Jin LU1(), Jian WANG1, Lian ZHU1, Guofeng YAN1, Zhengwen MA1, Yao LI1, Jianjun DAI2, Yinqiu ZHU1, Jing ZHOU1()()   

  1. 1.Department of Laboratory Animal Science, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
    2.Institution of Animal Husbandry & Veterinary Science, Shanghai 201106, China
  • Received:2023-03-21 Revised:2023-06-06 Published:2023-08-25 Online:2023-09-14
  • Contact: ZHOU Jing (ORCID: 0009-0005-2626-1561), E-mail: zj2008@shsmu.edu.cn

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模型,并获得了该模型的相关生理指标数据,进一步验证了先兆子痫疾病与子宫动脉病变的相关性。

关键词: 先兆子痫, 动物模型, 血流分析, 生物学特性, 山羊

Abstract:

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 group (P<0.05,P<0.01). Compared with the control group, the ewes in the surgical group showed prenatal changes such as increased serum osmolality, decreased hemoglobin, increased blood glucose and urea nitrogen values, as well as increased levels of calcium, sodium, and chloride ions (all P<0.05) and proteinuria, with urinary creatinine and urinary protein-creatinine ratios were significantly higher than those in the control group and sham group (all P<0.05). The elastic lamina of the uterine body arteries on the operated side of the animals in the surgical group was thicker than that on the opposite side, but the structure was loose. The placenta on the operated side showed pathological changes such as cell interstitial swelling and inflammatory cell infiltration. The above physiological index characteristics were more consistent with the clinical features of human preeclampsia disease. Conclusion In this experiment, we successfully constructed a goat preeclampsia model and obtained data on relevant physiological indexes of this model, which further verified the correlation between preeclampsia disease and uterine artery lesions.

Key words: Preeclampsia, Animal model, Blood flow analysis, Biological characteristics, Goat

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