Celastrol attenuates symptoms of preeclampsia in rats by inhibiting matrix metalloproteinase-9

Abstract

Preeclampsia is reported in pregnant women around the world and often causes maternal/fetal mortality and morbidity. In the current study, we assessed the efficacy of celastrol on a rat preeclampsia model induced by Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME). Pregnant rats were administered L-NAME to establish preeclampsia. A total of 48 animals were randomly assigned into 4 groups (n = 12 each): control, control plus celastrol treatment (control+celastrol), preeclampsia, and preeclampsia plus celastrol. Physiological parameters including total urine protein, urine volume and blood pressure were evaluated. Urinary messenger RNA (mRNA) levels of podocin and nephrin were determined using RT-PCR. Further, levels of serum placenta growth factor (PlGF), matrix metalloproteinase (MMP)-9 and renal renal soluble fms-like tyrosine kinase-1 (sFlt-1) were also measured. In rats with preeclampsia, there were robust increases in total urine protein, urine volume and blood pressure, which were significantly attenuated in rats treated with celastrol. Urinary mRNA levels of podocin and nephrin, as well as PlGF, MMP-9 and sFlt-1, were all reversed in preeclampsia plus celastrol group compared to rats in the preeclampsia group without celastrol treatments. MMP-9 overexpression in rats completely abolished the alleviating effect of celastrol. We hereby presented the first evidence that celastrol attenuated preeclampsia symptoms in an L-NAME-induced rat model of preeclampsia through inhibition of MMP-9 expression, supporting the potential therapeutic value of celastrol in the treatment of preeclampsia.