Govender Nalini, Ramdin Sapna, Reddy Rebecca, Naicker Thajasvarie
Department of Basic Medical Sciences, Faculty of Health Sciences, Durban University of Technology, Durban, South Africa.
Discipline of Optics and Imaging, Doris Duke Medical Research Institute, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.
Clin Exp Reprod Med. 2021 Jun;48(2):124-131. doi: 10.5653/cerm.2020.04035. Epub 2021 May 12.
Approximately 30% of preeclamptic pregnancies exhibit abnormal liver function tests. We assessed liver injury-associated enzyme levels and circulating transforming growth factor beta (TGF-β) levels in an arginine vasopressin (AVP)-induced pregnant Sprague-Dawley rat model.
Pregnant and non-pregnant Sprague-Dawley rats (n=24) received AVP (150 ng/hr) subcutaneously via mini-osmotic pumps for 18 days. Blood pressure was measured, urine samples were collected, and all animals were euthanized via isoflurane. Blood was collected to measure circulating levels of TGF-β1-3 isomers and liver injury enzymes in pregnant AVP (PAVP), pregnant saline (PS), non-pregnant AVP (NAVP), and non-pregnant saline (NS) rats.
The PAVP group showed significantly higher systolic and diastolic blood pressure than both saline-treated groups. The weight per pup was significantly lower in the AVP-treated group than in the saline group (p<0.05). Circulating TGF-β1-3 isomer levels were significantly higher in the PAVP rats than in the NS rats. However, similar TGF-β1 and TGF-β3 levels were noted in the PS and PAVP rats, while TGF-β2 levels were significantly higher in the PAVP rats. Circulating liver-type arginase-1 and 5'-nucleotidase levels were higher in the PAVP rats than in the saline group.
This is the first study to demonstrate higher levels of TGF-β2, arginase, and 5'-nucleotidase activity in PAVP than in PS rats. AVP may cause vasoconstriction and increase peripheral resistance and blood pressure, thereby elevating TGF-β and inducing the preeclampsia-associated inflammatory response. Future studies should explore the mechanisms through which AVP dysregulates liver injury enzymes and TGF-β in pregnant rats.
约30%的子痫前期妊娠表现出肝功能检查异常。我们在精氨酸加压素（AVP）诱导的妊娠Sprague-Dawley大鼠模型中评估了肝损伤相关酶水平和循环转化生长因子β（TGF-β）水平。
将妊娠和未妊娠的Sprague-Dawley大鼠（n = 24）通过微型渗透泵皮下给予AVP（150 ng/小时），持续18天。测量血压，收集尿液样本，所有动物通过异氟烷安乐死。采集血液以测量妊娠AVP（PAVP）、妊娠生理盐水（PS）、未妊娠AVP（NAVP）和未妊娠生理盐水（NS）大鼠的循环TGF-β1 - 3异构体水平和肝损伤酶。
PAVP组的收缩压和舒张压显著高于两个生理盐水处理组。AVP处理组每只幼崽的体重显著低于生理盐水组（p<0.05）。PAVP大鼠的循环TGF-β1 - 3异构体水平显著高于NS大鼠。然而，PS和PAVP大鼠的TGF-β1和TGF-β3水平相似，而PAVP大鼠的TGF-β2水平显著更高。PAVP大鼠的循环肝型精氨酸酶-1和5'-核苷酸酶水平高于生理盐水组。
这是第一项证明PAVP大鼠中TGF-β2、精氨酸酶和5'-核苷酸酶活性水平高于PS大鼠的研究。AVP可能导致血管收缩，增加外周阻力和血压，从而升高TGF-β并诱导子痫前期相关的炎症反应。未来的研究应探索AVP在妊娠大鼠中调节肝损伤酶和TGF-β失调的机制。
