脑源性神经营养因子在小鼠肠神经-平滑肌重构中的作用及其对肠动力的影响  

Role of brain-derived neurotrophic factor in the plasticity of enteric nervous-smooth muscle and its effects on gastrointestinal motility in mice

作　　者：陈飞雪[1] 于岩波[1] 王鹏[1] 左秀丽[1] 李延青[1] 

机构地区：[1]山东大学齐鲁医院消化科,济南250012

出　　处：《中华消化杂志》2016年第2期101-106,共6页Chinese Journal of Digestion

基　　金：国家自然科学基金青年基金（81400597）

摘　　要：目的观察脑源性神经营养因子（BDNF）在小鼠肠神经-平滑肌重构中的作用，并探讨BDNF引起的重构对小鼠肠动力的影响。方法取雄性杂合BDNF基因敲除（BDNF^＋/－）小鼠和野生型（BDNF^＋/＋）小鼠各8只，比较两种小鼠的肠道动力。制备小鼠结肠平滑肌纵肌条，观察卡巴胆碱（1×10^-5 mol/L）与BDNF （1×10^-7 mol/L）对小鼠肌条收缩活性的影响，并观察神经毒素河鲀毒素（1×10^-6 mol/L）对BDNF引起的肌条收缩活动的影响。免疫组织化学技术检测小鼠肠道肌间神经丛密度改变与肠平滑肌α-平滑肌肌动蛋白（α-SMA）表达量的变化。透射电子显微镜观察肠神经、神经-平滑肌接头和平滑肌的超微结构改变。各组间比较采用两独立样本t检验或秩和检验。结果BDNF^＋/－小鼠的排便粪粒数[（3.80±0.75）粒]及粪便含水量[（39.60±1.47）%]均低于BDNF^＋/＋小鼠[（6.30±1.03）粒，（51.00±1.61）%]，差异均有统计学意义（t＝4.792、12.827，P均〈0.05）；卡巴胆碱可明显增强BDNF^＋/＋小鼠与BDNF^＋/－小鼠的平滑肌收缩活性，两组小鼠的平均张力效应值与对照值的比值（R值）分别从1增至3.26±0.43和2.15±0.36，与加入药物前比较，差异均有统计学意义（t＝15.754、9.632，P均〈0.05）。对BDNF^＋/＋小鼠平滑肌条的收缩兴奋效应更加显著，差异有统计学意义（t＝5.972，P〈0.05）。BDNF可以增强BDNF^＋/＋小鼠肌条的收缩，R值从1增至1.41±0.09，差异有统计学意义（t＝13.674，P〈0.05），河鲀毒素预孵育可显著抑制BDNF的兴奋效应，R值从1.41±0.09降至1.03±0.04，差异有统计学意义（t＝11.692，P〈0.05）。BDNF^＋/－小鼠肠肌间神经丛密度明显低于BDNF^＋/＋小鼠[5.8%（4.2%，7.0%）比9.0%（7.1%，10.8%）]，差异有统计学意义（Z＝3.730，P〈0.05）；BDNF^＋/－小鼠肠平滑肌α-SMA表达量亦明显低于BDNF^＋/＋小鼠[33.4%（28.Objective To observe the role of brain-derived neurotrophic factor （BDNF） in the plasticity of enteric nervous-smooth muscle system, and to investigate the effects of BDNF induced plasticity on gastrointestinal motility in mice. Methods Male hybrid BDNF knockout （BDNF^＋/- ） mice and wild type （BDNF^＋/＋ ） mice were selected, eight in each group. Gastrointestinal motility of BDNF^＋/＋ mice and BDNF^＋/- mice were tested and compared. Longitudinal muscle strips of mice colon smooth muscle were prepared. The effects of carbachol （1×10^-5 mol/L） and BDNF （1× 10^-7 mol/L） on contractile function of muscle strips were observed. And the effects of tetrodotoxin （TTX, 1×10^-6 mol/L） on BDNF induced contractile function of muscle strips were also studied. The changes of the density of mice intestinal myenteric plexus and the expression of smooth muscle α-actin （α-SMA） in colon smooth muscle were detected by immunohistochemical techniqne. The ultrastructural alterations of myenteric plexus, neuromuscular junction （NMJ） and smooth muscle ceils were detected by transmission electron microscope （TEM）. T-test or Rank sum test was performed for comparison between groups. Results Number of feces particles and water content in feces of BDNF^＋/- mice （（3.80 ± 0.75） and （39.60 ±1.47）%） were both lower than those of BDNF^＋/＋ mice （（6. 30±1.03） and （51.00±1.61）%）, and the differences were statistically significant （t = 4. 792, 12. 827; both P〈0.05）. Carbachol （1×10^-5 mol/L） could significantly increase contraction activity of smooth muscle of BDNF^＋/＋ mice （R = 3. 26±0. 43） and BDNF^＋/- mice （R=2. 15±0. 36）, and the difference was statistically significant （t = 15. 754, 9. 632; both P〈0.05）. The effects on contraction exciting of smooth muscle strips of BDNF^＋/＋ mice were more significant than BDNF^＋/- mice, and the difference was statistically significant （t = 5. 972, P〈0. 05）. BDNF could significantly inc

关 键 词：脑源性神经营养因子 肠神经系统 平滑肌重构 胃肠活动 小鼠 

分 类 号：R965[医药卫生—药理学]