Study on the improvement effect of asiaticoside on pregnancy-induced hypertension rats by regulating the cAMP/PKA signaling pathway
Objective To investigate the mechanism of action of asiaticoside(AS)on pregnancy-induced hyperten-sion(PIH)rats by regulating the cyclic adenosine monophosphate/protein kinase A(cAMP/PKA)signaling pathway.Methods A PIH rat model was established and grouped into a Control group,a model group(PIH group),low,medium,and high dose groups of asiaticoside[AS-L,AS-M,AS-H groups,10,30,50 mg/(kg·d)AS],and a high-dose asiaticoside+PKA inhibitor H89 group[AS-H+H89 group,50 mg/(kg·d)AS+1 mg/kg H89].The animal blood pressure meter was applied to detect the SBP,DBP,MAP and the 24-hour urine protein(24 UTP)content of rats.ELISA was applied to detect the levels of TNF-α,IL-6,IL-10,β-HCG,PLGF,sFlt-1,ET-1,VEG Fand cAMP.The level of total NOx were measured,the fetal and placental weight and number of births was recorded.Immunohistochemistry was used to detect the expression of VEGF and GATA-3.The mRNA expression of NLRP3 was determined by RT-PCR.The protein expression of PKA,p-PKA,and NLRP3 was determined by Western blotting.Results Compared with the Control group,the levels of SBP,DBP,MAP,24 UTP,TNF-α,IL-6,β-HCG,ET-1,and sFlt-1,and the NLRP3 mRNA and protein expression levels were significantly higher in the PIH group(P＜0.05),the fetal and placental weights,number of births,the levels of IL-10,PLGF,VEGF,NOx and cAMP,the expression of VEGF and GATA-3,and the phosphorylation level of PKA were significantly lower(P＜0.05).Compared with the PIH group,the levels of SBP,DBP,MAP,24 UTP,TNF-α,IL-6,β-HCG,ET-1,and sFlt-1,and the NLRP3 mRNA and protein expression levels were significantly lower in the AS-L group,AS-M group,and AS-H group(P＜0.05),the fetal and placental weights,number of births,the levels of IL-10,PLGF,VEGF,NOx and cAMP,the expression of VEGF and GATA-3,and the phosphorylation level of PKA were significantly higher(P＜0.05),and were dose-dependent.H89 reversed the protective effect of asiaticoside on pregnant hypertensive rats(P＜0.05).Conclusion Asiaticoside can improve the symptoms of pregnancy-induced hypertension in rats by activating the cAMP/PKA signaling pathway.
asiaticosidecyclic adenosine monophosphate/protein kinase A signaling pathwaypregnancy-induced hypertension
万方数据
维普
