Protective effect of breviscapine against brain injury induced by intrauterine inflammation in preterm rats and its mechanism / 中国当代儿科杂志

OBJECTIVES@#To study the protective effect of breviscapine against brain injury induced by intrauterine inflammation in preterm rats and its mechanism.@*METHODS@#A preterm rat model of brain injury caused by intrauterine inflammation was prepared by intraperitoneal injections of lipopolysaccharide in pregnant rats. The pregnant rats and preterm rats were respectively randomly divided into 5 groups: control, model, low-dose breviscapine (45 mg/kg), high-dose breviscapine (90 mg/kg), and high-dose breviscapine (90 mg/kg)+ML385 [a nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor, 30 mg/kg] (n=10 each). The number and body weight of the live offspring rats were measured for each group. Hematoxylin-eosin staining was used to observe the pathological morphology of the uterus and placenta of pregnant rats and the pathological morphology of the brain tissue of offspring rats. Immunofluorescent staining was used to measure the co-expression of ionized calcium binding adaptor molecule-1 (IBA-1) and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) in the cerebral cortex of offspring rats. ELISA was used to measure the levels of interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-1β (IL-1β) in the brain tissue of offspring rats. Western blotting was used to measure the expression of Nrf2 pathway-related proteins in the brain tissue of offspring rats.@*RESULTS@#Pathological injury was found in the uterus, and placenta tissue of the pregnant rats and the brain tissue of the offspring rats, and severe microglia pyroptosis occurred in the cerebral cortex of the offspring rats in the model group. Compared with the control group, the model group had significant reductions in the number and body weight of the live offspring rats and the protein expression levels of Nrf2 and heme oxygenase-1 (HO-1) in the brain tissue of the offspring rats (P<0.05), but significant increases in the relative fluorescence intensity of the co-expression of IBA-1 and NLRP3, the levels of the inflammatory factors IL-6, IL-8, and IL-1β, and the protein expression levels of NLRP3 and caspase-1 in the brain tissue of the offspring rats (P<0.05). Compared with the model group, the breviscapine administration groups showed alleviated pathological injury of the uterus and placenta tissue of the pregnant rats and the brain tissue of the offspring rats, significant increases in the number and body weight of the live offspring rats and the protein expression levels of Nrf2 and HO-1 in the brain tissue of the offspring rats (P<0.05), and significant reductions in the relative fluorescence intensity of the co-expression of IBA-1 and NLRP3, the levels of the inflammatory factors IL-6, IL-8, and IL-1β, and the protein expression levels of NLRP3 and caspase-1 in the brain tissue of the offspring rats (P<0.05). The high-dose breviscapine group had a significantly better effect than the low-dose breviscapine (P<0.05). ML385 significantly inhibited the intervention effect of high-dose breviscapine (P<0.05).@*CONCLUSIONS@#Breviscapine can inhibit inflammatory response in brain tissue of preterm rats caused by intrauterine inflammation by activating the Nrf2 pathway, and it can also inhibit microglial pyroptosis and alleviate brain injury.

Association with Ductus Arteriosus Closure by Ibuprofen and Intrauterine Inflammation in Very Low Birth Weight Infants / 대한주산의학회잡지

PURPOSE: Ibuprofen is an inhibitor of prostaglandin synthesis and used to close a patent ductus arteriosus (PDA) of preterm infants. This study investigated the association between the response to ibuprofen treatment for PDA and maternal intrauterine inflammation in preterm infants. METHODS: We retrospectively reviewed the medical records of very low birth weight (VLBW) infants diagnosed with PDA, who are admitted immediately after birth in the neonatal intensive care unit at Dongguk University Ilsan Hospital between March 2010 and May 2013. After the first cycle of ibuprofen therapy, infants whose ductus arteriosus was closed and not closed were classified as Responders and Non-responders I, respectively. After the second cycle of ibuprofen therapy, infants with persistent PDA were classified as Non-responders II. We performed multiple logistic regression analysis to determine the most important factor associated with persistent PDA. RESULTS: After the first cycle of ibuprofen therapy, the numbers of Responders and Non-responders I were 40 and 14, respectively. Rate of cesarean section was significantly lower in Non-responders I than that of Responders (P=0.023). In addition, Rate of maternal amnionitis in Non-responder I was significantly higher than that of Responders (P=0.016). By multiple logistic regression analysis, maternal amnionitis was found to be a significant risk factor of the failure of ductus arteriosus closure after the first cycle of ibuprofen treatment (P=0.039). CONCLUSION: The present study shows that maternal amnionitis is an independent risk factor for the treatment failure after the first cycle of ibuprofen therapy in VLBW infants with PDA.