2022, Vol. 26 ›› Issue (29): 4651-4657

Effects of metformin on cognitive dysfunction in preeclampsia rats

Zhao Junguo1, Chen Xin1, Jiang Ruohan1, Guo Ying1, Gao Bo1, 2   

Abstract: BACKGROUND: Preeclampsia is a unique syndrome of pregnancy involving multiple organ systems, with no final conclusion in its pathogenesis. Endothelial dysfunction is a mechanism that has been widely used in basic research. Therefore, NG-nitro-L-arginine methyl ester was used in this study for preeclampsia modeling, followed by treatment with metformin.
OBJECTIVE: To establish the model of preeclampsia in rats by intraperitoneal injection of NG-nitro-L-arginine methyl ester, and to explore the effects of metformin on preeclampsia and cognitive function in rats.
METHODS: Pregnant rats were randomly divided into control group, model group, and metformin group. The model group was intraperitoneally injected with NG-nitro-L-arginine methyl ester in the middle and late pregnancy, and the metformin group was intraperitoneally injected with the same dose of NG-nitro-L-arginine methyl ester and metformin in the middle and late pregnancy. Body mass of each pregnant rat was recorded and corresponding drug dose was calculated every day. Caudal artery blood pressure was measured, and soluble endothelin and placental growth factor levels were quantified on day 19 of gestation and on days 10 and 30 after delivery. On the 19th day of gestation, urine was collected for 24 hours for urinary albumin and creatinine quantification. The Morris water maze test was conducted on the 10th and 30th days after delivery to obtain the escape latency, number of platform crossings and the average time spent in the target site where the platform was located.
RESULTS AND CONCLUSION: Intraperitoneal injection of NG-nitro-L-arginine methyl ester could successfully establish the preeclampsia model in rats, resulting in hypertension, proteinuria and intrauterine growth restriction and endothelial dysfunction. Metformin could improve the preeclampsia-like performance induced by NG-nitro-L-arginine methyl ester. NG-nitro-L-arginine methyl ester-induced preeclampsia rats presented with impaired cognitive function 10 and 30 days after delivery, and metformin treatment could improve the above performance to a certain extent. Therefore, metformin has certain potential in the treatment and prevention of preeclampsia, and its mechanism of action needs to be further studied.
Key words: preeclampsia, metformin, NG-nitro-L-arginine methyl ester, endothelial dysfunction, cognitive function, rat