Effects of rosmarinic acid on inflammation and endothelial dysfunction in preeclampsia rats
Objective To explore the therapeutic effect and its mechanism of rosmarinic acid(RA)on preeclampsia(PE)rats.Methods Starting from the 11 th day of pregnancy,pregnant rats were subcutaneously injected with L-nitroarginine methyl ester(L-NAME,200 mg/kg)every day for four consecutive days to establish a PE rat model,and then 30 model rats were randomly divided into three groups:model group,50RA group and 100RA group,with 10 rats in each group.Another 10 pregnant rats were selected as control group.At pregnant day 15,the rats in 50RA group and 100RA group were given 50 mg/kg RA and 100 mg/kg RA by gavage,respec-tively,and the rats in control group and model group were given normal saline by gavage for seven consecutive days.At pregnant day 21,systolic blood pressure(SBP),24 h urine protein,fetal body weight and mortality in each group were detected,the placental tissue was stained with hematoxylin-eosin(HE),and the kidney tissue was stained with periodic acid-Schiff(PAS)staining.Superoxide dismutase(SOD)and malondialdehyde(MDA)levels in serum of rats were detected with the kits.The serum levels of interleukin(IL)-1 β,IL-6,interferon-γ(IFN-y)and monocyte chemoattractant protein-1(MCP-1)in rats were detected using ELISA kits.Western blot was used to detect protein expressions of intercellular adhesion molecule-1(ICAM-1),leukocyte function-related antigen-1(LFA-1),vascular cell adhesion molecule-1(VC AM-1),Toll-like receptor 4(TLR4)and myeloid differentiation factor 88(MyD88).Results Compared with control group,SBP and 24 h urinary protein levels were increased in model group(P＜0.05),fetal body weight was decreased(P＜0.05),fetal mortality was increased(P＜0.05),there was significant damages in placenta and kidney tissue,serum level of SOD was decreased(P＜0.05),MDA level was increased(P＜0.05),serum lL-1 β,IL-6,IFN-y and MCP-1 levels were increased(P＜0.05),and the protein expression levels of ICAM-1,LFA-1,VCAM-1,TLR4 and MyD88 in placental tissue were increased(P＜0.05).Compared with model group,SBP and 24 h urinary protein levels were decreased in 50RA group and 100RA group(P＜0.05),fetal body weight was increased(P＜0.05),fetal mortality was decreased(P＜0.05),the damages of placenta and kidney tissues were significantly improved,serum level of SOD was increased(P＜0.05),MDA level was decreased(P＜0.05),serum IL-1 β,IL-6,IFN-γ and MCP-1 levels were decreased(P＜0.05),and the protein expressions of ICAM-1,LFA-1,VCAM-1,TLR4 and MyD88 in placental tissue were decreased(P＜0.05).Compared with 50RA group,SBP and 24 h urinary protein levels were decreased in 100RA group(P＜0.05),fetal body weight was increased(P＜0.05),the damages of placenta and kidney tissues were significantly improved,serum level of SOD was increased(P＜0.05),MDA level was decreased(P＜0.05),serum IL-1β,IL-6,IFN-γ and MCP-1 levels were decreased(P＜0.05),and the protein expressions of ICAM-1,LFA-1,VCAM-1,TLR4 and MyD88 in placental tissue were decreased(P＜0.05).Conclusion RA can effectively alleviate the pathological changes of PE rats,and RA may exert its thera-peutic effect on PE by reducing inflammation,oxidative stress and endothelial dysfunction mediated by TLR4 signaling pathway.
万方数据
维普
