目的观察神经调节素B受体激动剂(NMBR)对孕鼠孕龄的影响并探讨其影响机制。方法建立孕龄准确的孕鼠模型,随机分组,每组10只。妊娠18d2、6:00pm分别腹腔注射NMB(30、90、150μg·kg^-1)、缩宫素(50mlU·kg^-1)及等体积的溶剂,连续2d,观察孕鼠孕龄及分娩间隔。妊娠18d6、8、10、12:00am分别给予上述处理,末次给药后4h取孕鼠子宫平滑肌组织,用NoShift转录因子分析法检测NF—KBP65的DNA结合活性,用半定量RT—PCR和Westernblot检测HSP70及IL-6mRNA和蛋白表达。结果150μg·kg^-1 NMBR组孕龄明显短于对照组和低剂量组(P〈0.05);且NF—KBP65DNA结合活性、HSP70及IL-6mRNA表达水平明显高于对照组(P〈0.05)。结论NMBR激动剂可能通过子宫平滑肌NF—kBP65-HSP70/IL-6通路缩短孕鼠的孕龄。
Aim To observe the effects of neuromedin B receptor (NMBR) agonist on gestational age in mice and investigate its mechanism. Methods Pregnant mice model was prepared. The pregnant mice were randomly assigned into 10 groups. Five groups were administrated 30, 90 and 150 μg · kg^-1 NMBR treatment, oxytocin (50 mIU · kg^- 1 ) and solvent treatment (control). After treatment at 2 and 6:00 pm on gestational days 18 and 19, gestational age and delivery interval were monitored and recorded (n = 10 in each group). The remaining pregnant mice divided into five groups were received treatment at 6, 8, 10, and 12:00 am on gestational day 18. After 4 hours since the last injection, myometrium was harvested. NF-kB P65 DNA binding activities were detected by NoShift transcription factor assay. The expression of HSP70 and IL-6 mRNA and protein were measured by semi-quantitative RT-PCR and Western blot, respectively. Results The gestational age of the 150 μg · kg^-1 NMBR group was significantly shorter than that of the low-dose NMBR group and the control group (P 〈 0.05). NF- kB P65 DNA binding activity and expressive levels of HSP70 and IL-6 mRNA in the 150 μg · kg^-1 NMBR treatment group were significantly higher than that of the control group ( P 〈 0. 05 ). Conclusions High concentration of NMBR agonist can shorten gestational age, possibly through a mediation of NF-kB P65- HSP70/IL-6 pathway in the myometrium in mice.