YANG Xuan, ZHANG Wenjuan, XIA Li.
Objective To investigate the impacts of gastrodin (Gas) on placental angiogenesis and pregnancy outcomes in pregnancy induced hypertension (PIH) rats by regulating the Notch pathway. Methods A PIH model was constructed by subcutaneous injection of L-arginine methyl ester (L-NAME) into pregnant rats, after successful modeling, the model was grouped into model group, Gas low, medium, and high dose groups (50, 100, 200 mg/kg), and inhibitor group (Gas 200 mg/kg+Notch pathway inhibitor gamma-secretase inhibitor 500) using a random number table method μg/100 g), 12 mice/group, 12 pregnant mice of the same period were regarded as the control group, and each group was injected with corresponding drugs intraperitoneally, once a day for one consecutive week. Blood pressure measuring instruments and pyrogallol red method were applied to detect tail vein pressure and 24-hour urine protein in late pregnancy, respectively; cesarean section was performed on the 24 th day of pregnancy, and the pregnancy outcome was recorded; Hematoxylin eosin staining was applied to observe pathological changes in placental tissue; CD34 staining was applied to detect the number and density of microvessels in placental tissue; enzyme-linked immunosorbent assay was applied to detect levels of interleukin (IL)-6, IL-1β, and tumor necrosis factor-α (TNF-α) in placental tissue; Western blot was applied to detect the expression of vascular endothelial growth factor (VEGF) and Notch pathway proteins in placental tissue. Results Compared with the model group, 24-hour urine protein, the tail vein pressure, IL-1β, IL-6, and TNF-α levels in the low, medium, and high dose Gas groups were reduced, the average fetal rats mass, average offspring number, microvessel quantity (MVQ), microvessel density (MVD), VEGF, Notch1, Jagged1, hes family bHLH transcription factor 1 (HES1) expression were increased, there was a statistical difference between each group (P<0.05); compared with the high-dose gas group, the changes in the above indicators in the inhibitor group were reversed (P<0.05). Conclusions Gas has the effects of inhibiting inflammation, promoting angiogenesis in PIH rats, and improving pregnancy outcomes. Its mechanism of action may be related to the activation of the Notch pathway.
