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Tetramethylpyrazine reduces the consequences of nitric oxide inhibition in pregnant rats |
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| Authors: | Shengyi Gu Huaxiang Shen Yun Zhou Jiaying Ni Tao Zheng Zhengqian Mou Xiaolin Hua |
| Institution: | 1. Department of Obstetrics and Gynecology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
Department of Obstetrics, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China Gu and Shen have contributed equally to this study.;2. Department of Obstetrics, Jiaxing Maternity and Child Health Hospital, Jiaxing, Zhejiang, China Gu and Shen have contributed equally to this study.;3. Department of Obstetrics and Gynecology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China;4. Department of Obstetrics and Gynecology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China Department of Obstetrics, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China;5. Department of Obstetrics, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China |
| Abstract: | Pre-eclampsia (PE) is closely associated with perinatal morbidity and mortality and we want to investigate tetramethylpyrazine (TMP)'s effects on PE. Pregnant Sprague–Dawley rats were randomly divided into five groups: normal pregnant (PC), PE, PE+TMP 20 mg/kg, PE+TMP 40 mg/kg, and PE+TMP 60 mg/kg group. The PE rat model was established via L-NAME treatment. Systolic blood pressures (SBP) and urinary protein concentration were detected via the tail-cuff method and CBB kit, respectively. mRNA levels of key genes were analyzed via quantitative PCR and protein levels of key genes were measured by ELISA or western blot. TMP decreased SBP and urinary protein concentration of PE rats. TMP inhibited L-NAME-induced decrease in pups alive ratio, pups weight, and the ratio of pups/placenta weight and reversed L-NAME induced changes in placental histology, whereas it had little effect on placental weight. Urinary nephrin and podocin expressions were enhanced and serum placental growth factor level was decreased in PE rats, whereas TMP inhibited the above phenomena. TMP suppressed L-NAME-induced sFlt-1 upregulation in serums and kidneys of PE rats, whereas it downregulated IL-6 and MCP-1 expression in PE rats' serums, placentas and kidneys. TMP also suppressed the increase in placental sFlt-1 and vascular endothelial growth factor level caused by L-NAME. In addition, TMP inhibited CHOP and GRP78 expressions and decreased the ratio of p-elF2α/elF2α in PE rats. TMP attenuated the consequences of NO inhibition in pregnant rats. |
| Keywords: | ER stress hypertension pre-eclampsia proteinuria tetramethylpyrazine |