BDNF对脓毒症相关性脑病大鼠学习记忆功能的改善作用

Effects of BDNF on improving cognitive dysfunction in rats with sepsis-associated encephalopathy

目的:探讨脑源性神经营养因子(BDNF)对脓毒症相关性脑病(SAE)大鼠的学习记忆功能的影响及其机制。方法:采用盲肠结扎穿孔法(CLP)建立脓毒症相关性脑病模型,取成年雄性SD大鼠40只随机分为4组,每组10只:假手术组(Sham组)、模型组(CLP组)、BDNF组(B组)、酪氨酸激酶B受体拮抗剂组(N组)。于造模前Sham组和CLP组侧脑室注射5μL生理盐水,B组注射BDNF(2 ng/μL)5μL,N组注射酪氨酸激酶B受体(Trk B)拮抗剂NTrk2(1μg/μL)5μL后再行盲肠结扎穿孔制作脓毒症大鼠模型,术后第2~6天行Morris水迷宫定位航行训练,术后第7天行空间探索实验。结果:与Sham组比较,CLP组、N组大鼠逃避潜伏期延长(P<0.05),CLP组、B组、N组目标象限停留时间占全象限停留时间比以及探索次数明显减少(P<0.05);与Sham组比较,CLP组、N组虚拟平台穿越次数减少(P<0.05),与CLP组比较,B组平台穿越次数增多(P<0.05);4组大鼠在游泳速度上差异无统计学意义。结论:脓毒症可致大鼠认知功能受损,BDNF可改善脓毒症相关性脑病大鼠的学习记忆功能,其机制可能与BDNF-Tr KB信号通路有关。

Objective ：To investigate the effects of brain derived neurotrophic factor（BDNF） on the learning and memory function in rats with sepsis and the potential mechanisms.Methods ： Forty male SD rats with sepsis induced by cecal ligation and puncture （CLP） were randomized into sham operation group （ sham group） , SAE model group （ CLP group） , BDNF group （ B group） and TrkB receptor antagonist group （ N group）.Before model establishment, rats in the sham group and CLP group were injected with saline via intracerebroventricle in dose of 5μL, and those in B group were administered with BDNF（2 ng/μL） in dose of 5 μL.Rats in N group were treated with the same volume of TrkB receptor antagonist （NTrk2,1 μg/μL）.Morris water maze test was performed to test the place navigation of rats from day 2 to 6, and space exploration test was performed by dayT.Results：Compared to the sham group, rats in CLP and N groups had longer escape latency（ P〈0.05 ）, and those in CLP, B and N groups had significantly reduced percentage of crossing target quadrant and exploring frequencies（P〈0.05）.Rats in CLP and N groups had reduced frequencies of platform crossing compared to those in sham group（P〈0.05） ,whereas rats in B group had higher number of times of crossing platform than those in CLP group（P〈0.05 ）.The swimming velocity re- mained no statistical difference in four groups.Conclusion：Damaged cognitive function of rats with sepsis-associated encephalopathy can be reversed by BDNF.The potential mechanism may be involved in BDNF-TrkB signaling pathway.