Effects of AKR1C3 on kidney damage of preeclamptic rats

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To explore the effects of AKR1C3 on kidney damage of preeclamptic rats and elucidate the possible therapeutic mechanism of glyburide. The rat model of preeclampsia was established by an intraperitoneal injection of Nw-nitro-L-arginine methyl ester hydrochloride (L-NAME). A total of 40 Wistar rats were randomly divided into 4 groups of preeclampsia (pregnant rats and L-NAME), treatment (pregnant rats, L-NAME and glyburide), non-pregnancy (L-NAME) and control (pregnant rats and NS) (n = 10 each). The rats in treatment group received an intragastric dose of glyburide. Successful modeling was confirmed by measuring blood pressure and 24 h urine protein content and observing the structure of kidney under transmission electron microscopy (TEM). The methods of reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were employed to detect the expression levels of AKR1C3, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA). The blood pressures of all rats had no significant difference prior to modeling. After modeling, the blood pressure of preeclampsia group was significantly higher than those of control and treatment groups [(143.83 ± 9.62), (120.83 ± 4.31), (129.43 ± 14.4) mmHg, both P < 0.05]. The 24 h urine protein content of all rats had no significant difference prior to modeling. After modeling, the 24 h urine protein content of preeclampsia group was higher than those of control and treatment groups. The TEM observation of kidney slices verified the success of modeling. In preeclampsia group, the expression levels of AKR1C3 in protein and mRNA were significantly lower than control group [(0.48 ± 0.09) vs (0.98 ± 0.27), (0.05 ± 0.02) vs (0.87 ± 0.45), both P < 0.05]. Compared with preeclampsia group, the expression levels of AKR1C3 in protein and mRNA significantly increased in treatment group [(0.48 ± 0.09) vs (1.05 ± 0.20), (0.05 ± 0.02) vs (0.22 ± 0.06), both P < 0.05]. As compared with control group, the levels of SOD, CAT and GSH-Px were significantly lower while MDA was higher. Compared with preeclampsia group, the levels of SOD, CAT and GSH-Px in treatment group were significantly higher while MDA was lower. The expression level of AKR1C3 decreases in kidney of preeclamptic rats and the mechanism is related with oxidative stress. Glyburide increases the expression of AKR1C3 and have therapeutic effect for preeclampsia.