Jin Ya, Sun Chengjuan, Zhang Weiyuan
Beijing Obstetrics & Gynecology Hospital, Capital Medical University, Beijing 100026, China.
Beijing Obstetrics & Gynecology Hospital, Capital Medical University, Beijing 100026, China. Email:
Zhonghua Yi Xue Za Zhi. 2015 Jan 6;95(1):30-3.
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.
探讨醛糖还原酶1C3（AKR1C3）对先兆子痫大鼠肾损伤的影响，并阐明格列本脲可能的治疗机制。
通过腹腔注射盐酸Nw-硝基-L-精氨酸甲酯（L-NAME）建立先兆子痫大鼠模型。将40只Wistar大鼠随机分为4组：先兆子痫组（孕鼠和L-NAME）、治疗组（孕鼠、L-NAME和格列本脲）、非孕组（L-NAME）和对照组（孕鼠和生理盐水）（每组n = 10）。治疗组大鼠给予格列本脲灌胃。通过测量血压、24小时尿蛋白含量并在透射电子显微镜（TEM）下观察肾脏结构来确认建模成功。采用逆转录-聚合酶链反应（RT-PCR）和蛋白质免疫印迹法检测AKR1C3、超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GSH-Px）和丙二醛（MDA）的表达水平。
建模前所有大鼠血压无显著差异。建模后，先兆子痫组血压显著高于对照组和治疗组[（143.83±9.62）、（120.83±4.31）、（129.43±14.4）mmHg，P均<0.05]。建模前所有大鼠24小时尿蛋白含量无显著差异。建模后，先兆子痫组24小时尿蛋白含量高于对照组和治疗组。肾脏切片的TEM观察证实建模成功。在先兆子痫组中，蛋白质和mRNA水平的AKR1C3表达均显著低于对照组[（0.48±0.09）对（0.98±0.27），（0.05±0.02）对（0.87±0.45），P均<0.05]。与先兆子痫组相比，治疗组蛋白质和mRNA水平的AKR1C3表达显著增加[（0.48±0.09）对（1.05±0.20），（0.05±0.02）对（0.22±0.06），P均<0.05]。与对照组相比，SOD、CAT和GSH-Px水平显著降低而MDA水平升高。与先兆子痫组相比，治疗组SOD、CAT和GSH-Px水平显著升高而MDA水平降低。
先兆子痫大鼠肾脏中AKR1C3表达水平降低，其机制与氧化应激有关。格列本脲可增加AKR1C3的表达，对先兆子痫具有治疗作用。
