Magnesium sulfate reduces vascular endothelial cell apoptosis in rats with preeclampsia via the miR-218-5p/HMGB1 pathway.

OBJECTIVE: This study aims to investigate the mechanism by which magnesium sulfate regulates the miR-218-5p/HMGB-pathway-mediated apoptosis of vascular endothelial cells (VECs) in rats with preeclampsia (PE). METHODS: Twenty pregnant rats were randomly divided into four groups: normal, PE, MgSO4, and high-mobility group protein B1 (HMGB1)-agomir groups. On the 14th day of each rat's pregnancy, endotoxin was used to establish a PE model in the PE, MgSO4, and HMGB1-agomir groups. Then, the MgSO4 and HMGB1-agomir groups were treated with magnesium sulfate. Finally, HMGB1 overexpression was performed only in the HMGB1-agomir group. The rats' urinary protein content and systolic blood pressure at 24 h were detected on the 11th, 13th, 15th, 17th, and 19th day of pregnancy. RESULTS: Compared with the PE group, 24-h urinary protein content, blood pressure, VEC apoptosis rate, apoptosis marker levels, and HMGB1 expression decreased while miR-218-5p levels increased in the MgSO4 group. The dual-luciferase assay revealed that HMGB1 can be targeted and regulated by miR-218-5p. Compared with the MgSO4 group, 24-h urinary protein content, blood pressure, VEC apoptosis rate, apoptosis marker levels, and HMGB1 expression increased while miR-218-5p levels decreased in the HMGB1-agomir group. CONCLUSION: MgSO4 reduces VEC apoptosis in PE rats via the miR-218-5p/HMGB1 pathway and thus plays a role in treating PE.

The function of P2X3 receptor and NK1 receptor antagonists on cyclophosphamide-induced cystitis in rats.

PURPOSE: The purpose of the study is to explore the function of P2X3 and NK1 receptors antagonists on cyclophosphamide (CYP)-induced cystitis in rats. METHODS: Sixty female Sprague-Dawley (SD) rats were randomly divided into three groups. The rats in the control group were intraperitoneally (i.p.) injected with 0.9% saline (4 ml/kg); the rats in the model group were i.p. injected with CYP (150 mg/kg); and the rats in the intervention group were i.p. injected with CYP with subsequently perfusion of bladder with P2X3 and NK1 receptors' antagonists, Suramin and GR 82334. Spontaneous pain behaviors following the administration of CYP were observed. Urodynamic parameters, bladder pressure-volume curve, maximum voiding pressure (MVP), and maximum cystometric capacity (MCC), were recorded. Pathological changes in bladder tissue were observed. Immunofluorescence was used to detect the expression of P2X3 and NK1 receptors in bladder. RESULTS: Cyclophosphamide treatment increased the spontaneous pain behaviors scores. The incidence of bladder instability during urine storage period of model group was significantly higher than intervention group (χ(2) = 7.619, P = 0.007) and control group (χ(2) = 13.755, P = 0.000). MCC in the model group was lower than the control and intervention groups (P < 0.01). Histological changes evident in model and intervention groups rats' bladder included edema, vasodilation, and infiltration of inflammatory cells. In model group, the expression of P2X3 receptor increased in urothelium and suburothelium, and NK1 receptor increased in suburothelium, while the expression of them in intervention group was lower. CONCLUSIONS: In CYP-induced cystitis, the expression of P2X3 and NK1 receptors increased in urothelium and/or suburothelium. Perfusion of bladder with P2X3 and NK1 receptors antagonists ameliorated the bladder function.