替米沙坦对脂多糖诱导的抑郁模型大鼠行为、脑内炎症反应及BDNF信号通路的影响

Telmisartan attenuates lipopolysaccharide-induced hippocampal neuroinflammation and depression-like behaviors in rats

目的对AT1受体阻断剂替米沙坦(TLM)的抗炎作用进行考察,并探究其潜在的抗抑郁作用。方法 SD大鼠随机分为3组:对照组、脂多糖(LPS)组和脂多糖+替米沙坦(LPS+TLM)组。LPS+TLM组连续5 d预先腹腔注射1 mg/(kg·d)的TLM,末次给药1 h后,LPS和LPS+TLM组均腹腔注射给予1次0.5 mg·kg^(-1)的LPS,而对照组给予相同体积的生理盐水。对大鼠的行为学进行考察,并对海马内炎症反应及BDNF-Trk B信号通路进行分析。结果 TLM改善了应激对大鼠行为学的改变,同时也抑制了LPS所导致的神经免疫激活,诱导了BDNF-Trk B信号通路。结论 TLM有潜在的抗炎及抗抑郁作用,并可以对BDNF-Trk B信号通路产生调控作用。

Objective To investigate the anti-inflammatory action of telmisartan （TLM） and explore its potential antidepression mechanisms. Methods Sprague-Dawley rats were randomly divided into 3 groups： a control group, a lipopolysaccharide （LPS） group, and a TLM ＋ LPS group. After 5 days of intraperitoneal injection of 1 mg · kg^-1 TLM, the rats in the LPS and the TLM ＋ LPS group were treated with LPS （0.5 mg · kg^-1）, while the control group was given the same volume of saline. Then we evaluated the behavioral changes and the ex- pression of inflammatory cytokines and BDNF-TrkB signaling. Results TLM effectively attenuated the LPS- induced depression-like behaviors and neuroinflammation. Meanwhile, the LPS-induced compromised BDNF- Trkt3 signaling was also restored by TLM pretreatment. Conclusion TLM has potential anti-inflammatory and antidepressant effect, and can modulate BDNF-TrkB signaling.