OBJECTIVETo investigate the role of nuclear factor-κB (NF-κB) activation in bilirubin-induced apoptosis of rat hippocampal neurons and the effect of TAT-NBD intervention on bilirubin neurotoxicity.

METHODSPrimary-cultured rat hippocampal neurons were treated with TAT-NBD in the initial 6 or 24 h or in the latter 6 h during a 24-h bilirubin exposure of the cells (early, continuous and late intervention groups, respectively). Immunocytochemistry was performed to detect NF-κB p65 protein expression, and the cell survival and apoptosis were assessed with a modified MTT assay, Annexin V-FITC/PI and TUNEL assay. IL-1β concentration in the supernatant was determined with ELISA.

RESULTSCompared with the control cells, bilirubin-treated cells showed a significantly increased NF-κB p65 protein expression (P<0.01), which reached the peak level at 6 and 24 h (P<0.01). The cell survival rate in early TAT-NBD intervention group was (80.784∓9.767)%, significantly lower than that of the control group (P<0.01) but higher than that of bilirubin group (P<0.01); the apoptotic rate in early TAT-NBD intervention group was significantly higher than that of control group (P<0.01) but lower than that of bilirubin group (P<0.01). IL-1β concentration was significantly lower in early TAT-NBD intervention group (15.348∓0.812 pg/ml) than in bilirubin group (P<0.05). The continuous and late TAT-NBD intervention groups showed comparable cell survival rate, apoptotic rate and IL-1β concentration with bilirubin group (P>0.05).

CONCLUSIONNF-κB bidirectionally regulates bilirubin-induced apoptosis of rat hippocampal neurons. Selective inhibition of the early peak of NF-κB by TAT-NBD offers neuroprotective effect. TAT-NBD can be potentially used for prophylaxis of bilirubin-induced brain injury.

Animals ; Apoptosis ; drug effects ; Bilirubin ; toxicity ; Cell Survival ; Cells, Cultured ; Female ; Hippocampus ; cytology ; Interleukin-1beta ; metabolism ; Male ; Neurons ; cytology ; drug effects ; metabolism ; Neuroprotective Agents ; pharmacology ; Peptides ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Transcription Factor RelA ; metabolism

Paeoniflorin is one of the bioactive components of Paeonia lactiflora, a traditional Chinese herbal medicine. Some recent studies prove its distinguished neuroprotective effect. These neuroprotective mechanisms have become hot points and show closely correlated to activating adenosine A1 receptor, ameliorating the function of cholinergic nerve, regulating ion channel homeostasis, retarding oxidative stress and apoptosis of the neurocytes, promoting nerve growth, having an influence on astrocytes and being ableto penetrate though blood brain barrier. In this review, we present the neuroprotective mechanisms of paeoniflorin in the following eight aspects.
Animals ; Apoptosis ; drug effects ; Benzoates ; analysis ; pharmacology ; Bridged-Ring Compounds ; analysis ; pharmacology ; Drugs, Chinese Herbal ; analysis ; pharmacology ; Glucosides ; analysis ; pharmacology ; Humans ; Monoterpenes ; Neurons ; cytology ; drug effects ; metabolism ; Neuroprotective Agents ; analysis ; pharmacology ; Oxidative Stress ; drug effects ; Paeonia ; chemistry

Objective:To study the levels of serum ferritin (SF) in preterm infants of different gestational ages and analyze the influencing factors.Method:From October 2018 to October 2020, preterm infants hospitalized in our hospital were included for prospective study. According to the gestational age, the infants were assigned into 3 groups: 34~36 w group, 32~33 w group and <32 w group. The SF levels were compared among the groups and the influencing factors were analyzed.Result:A total of 919 preterm infants were included, including 481 in the 34~36 w group, 293 in the 32~33 w group and 145 in the <32 w group. The incidence of Cesarean section in the <32 w group was lower than the other two groups ( P<0.001). The incidence of twin birth in the 32~33 w group was higher than the other two groups ( P<0.05). No significant differences existed in gender among the three groups ( P>0.05). The serum SF levels in the 34~36 w group, 32~33 w group and <32 w group were (240.1±167.4), (216.2±137.0) and (204.4±112.8)μg/L, respectively. The serum SF levels in the 34~36 w group were higher than the other two groups ( P<0.05). No significant differences existed in serum SF levels between the 32~33 w group and the <32 w group ( P>0.05). Multiple　linear　regression　analysis　showed　that SF levels were lower in premature infants with small gestational age and Cesarean section delivery ( P<0.05). Conclusion:SF levels in premature infants with small gestational age and Cesarean section delivery are lower and more monitoring of SF are needed.