Tetramethylpyrazine reduces the consequences of nitric oxide inhibition in pregnant rats

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. K E Y W O R D SER stress, hypertension, pre-eclampsia, proteinuria, tetramethylpyrazine

Esomeprazole inhibits hypoxia/endothelial dysfunction–induced autophagy in preeclampsia

“…PE has negative consequences on maternal and fetal health during pregnancy, including increased perinatal mortality, preterm births, infants who are considered small for gestational age, high rates of cesarean deliveries, and other adverse outcomes, even in later postnatal periods (Antza et al 2018 ; Gu et al 2019 ). The relevant mechanism is not yet fully elucidated.…”

“…Human tissue from control and PE placenta and cell lysates from HTR-8/Svneo cells, HUVEC cells, and mouse placentas from the control, PE, and treated-PE groups were detected by Western blotting, as previously described (Gu et al 2019 ). Proteins extracted from tissue and cell samples were fractionated on sodium dodecyl sulfate‐polyacrylamide gel and electrophoresis gels and transferred to polyvinylidene fluoride membranes.…”

“…Human tissue from control and PE placenta and cell lysates from HTR-8/Svneo cells, HUVEC cells, and mouse placentas from the control, PE, and treated-PE groups were detected by Western blotting, as previously described (Gu et al 2019).…”

Ligustrazine-induced microRNA-16-5p inhibition alleviates preeclampsia through IGF-2

“…(1) the LPS group (untreated); LPS + DMSO group: during PE modeling, DMSO solution (Sigma-Aldrich) was injected intraperitoneally from the 7th to 18th day of pregnancy at a dose of 60 mg/kg/day; (2) LPS + TMP group: during PE modeling, TMP injection (20 mg/mL, Wuxi No. 7 Pharmaceutical Factory, China) was injected intraperitoneally from the 7th to 18th day of pregnancy at a dose of 60 mg/kg/day (Gu et al 2019); (3) LPS + agomir-NC group: during PE modeling, lentiviral vectors containing negative control sequence of miR-16-5p agomir were injected into a rat tail vein from the 13th day to 18th day at a dose of 0.5 mg/kg/day; (4) LPS + agomir-16-5p group: during PE modeling, lentiviral vectors overexpressing miR-16-5p were injected into a rat tail vein from the 13rd day to 18th day at a dose of 0.5 mg/ kg/day; (5) agomir-NC + DMSO group: during PE modeling, the rats were injected intraperitoneally with DMSO solution at the dose of 60 mg/kg/day from the 7th to the 18th day of pregnancy, and the negative control of miR-16-5p agomir was injected into a tail vein at the dose of 0.5 mg/kg/day; (6) agomir-16-5p + DMSO group: during PE modeling, rats were injected intraperitoneally with DMSO solution from the 7th to the 18th day of pregnancy at a dose of 60 mg/ kg/day. From the 13th day to 18th day, lentiviral vectors overexpressing miR-16-5p was injected into a tail vein at a dose of 0.5 mg/kg/day; (7) agomir-16-5p + TMP group: during PE modeling, TMP solution was injected intraperitoneally at a dose of 60 mg/kg/day on the 7th to 18th days of pregnancy, and the lentiviral vectors overexpressing miR-16-5p was injected at a dose of 0.5 mg/kg/day through a tail vein from the 13th day to 18th day.…”

“…A prior study has suggested that TMP injections led to remarkable therapeutic effects on pregnancy-induced hypertension through repressing fibrinolysis and enhancing microcirculation (Wang & Zhao 2003). Moreover, TMP administration attenuates placental endoplasmic reticulum stress in PE rats (Gu et al 2019). However, the molecular mechanisms underlying the pharmacological actions of TMP remain uncharacterized.…”