Department of Nephrology, Shanghai Fifth People's Hospital, Fudan University, 801 Heqing Road, Shanghai 200240, P.R. China.
Department of Nephrology, Huashan Hospital, Fudan University, 12 Wulumuqi Zhong Road, Shanghai 200040, P.R. China.
Exp Anim. 2022 Nov 10;71(4):519-528. doi: 10.1538/expanim.22-0029. Epub 2022 Aug 8.
Preeclampsia (PE) is a multisystem disease that affects the health of both the pregnant women and the fetus during pregnancy. Agonistic autoantibodies to the angiotensin II type I receptor (AT1-AA) play a significant role in the pathogenesis of PE. This study aimed to determine the effects of Angiotensin 1-7 (Ang 1-7) and its analogue AVE0991 on AT1-AA-induced PE model. Pregnant mice were divided into five groups: the normal pregnant group, AT1-AA-induced preeclampsia group, and AT1-AA-induced preeclampsia group treated with Losartan, Ang 1-7, and AVE0991, respectively. AT1-AA-induced PE model was established on gestational day 13 by tail intravenous injection of purified AT1-AA polyclonal antibody from serum of guinea pigs. Blood urea nitrogen (BUN), urine albumin and urinary creatinine were measured on day 18 of pregnancy. The systolic blood pressure (SBP) was measured from gestational day 13 to day 18. Renal structure changes were observed via light and electron microscopy. Compared with the normal pregnant group (NP group), AT1-AA-induced preeclampsia group (PE group) exhibited elevated blood pressure and proteinuria, consistent with the characteristics of PE. Ang 1-7 or AVE0991 treatment decreased blood pressure without showing renoprotective effects. The findings indicated that Ang 1-7 and its analogue reduced blood pressure but aggravated renal damage in AT1-AA-induced PE mice.
子痫前期(PE)是一种多系统疾病,会影响孕妇和胎儿在怀孕期间的健康。血管紧张素 II 型 1 型受体(AT1-AA)的激动性自身抗体在 PE 的发病机制中起重要作用。本研究旨在确定血管紧张素 1-7(Ang 1-7)及其类似物 AVE0991 对 AT1-AA 诱导的 PE 模型的影响。将怀孕小鼠分为五组:正常妊娠组、AT1-AA 诱导的子痫前期组、以及分别用氯沙坦、Ang 1-7 和 AVE0991 治疗的 AT1-AA 诱导的子痫前期组。通过尾静脉注射来自豚鼠血清的纯化 AT1-AA 多克隆抗体,在妊娠第 13 天建立 AT1-AA 诱导的 PE 模型。在妊娠第 18 天测量血尿素氮(BUN)、尿白蛋白和尿肌酐。从妊娠第 13 天到第 18 天测量收缩压(SBP)。通过光镜和电子显微镜观察肾脏结构变化。与正常妊娠组(NP 组)相比,AT1-AA 诱导的子痫前期组(PE 组)血压升高和蛋白尿,符合 PE 的特征。Ang 1-7 或 AVE0991 治疗降低了血压,但没有显示出肾脏保护作用。这些发现表明,Ang 1-7 和其类似物降低了血压,但加重了 AT1-AA 诱导的 PE 小鼠的肾脏损伤。