右美托咪定抑制大鼠创伤性脑损伤后神经细胞凋亡

Dexmedetomidine Inhibits Neuronal Apoptosis after Traumatic Brain Injury in Rats

目的探讨右美托咪定(DEX)对创伤性脑损伤(TBI)的神经保护作用是否与抑制神经细胞凋亡有关,是否涉及SIRT1信号通路。方法将SD大鼠随机分为Sham组、TBI+NS组、TBI+DEX组和TBI+DEX+EX527组。采用干/湿重法评估脑创伤后脑组织含水量;神经功能缺损评分检查神经功能受损情况;Western blot法检测大鼠皮质Bcl-2和Bax蛋白的表达水平。结果实验结果显示DEX干预后可减少脑创伤后促凋亡的调控蛋白Bax表达,差异有统计学意义(P<0.05),增加抑制凋亡的调控蛋白Bcl-2表达,差异有统计学意义(P<0.05),减轻脑水肿,差异有统计学意义(P<0.05)和改善神经功能,差异有统计学意义(P<0.05),上述观测指标的变化可被SIRT1抑制剂EX527逆转。结论提示DEX通过抑制神经细胞凋亡而减轻脑创伤后的继发性损害,该神经保护作用与SIRT1信号通路之间存在一定相关性。

Objective To discuss whether the neuroprotective effect of dexmedetomidine(DEX)against traumatic brain injury(TBI)is related to the inhibition of neuronal apoptosis and whether it is involved in SIRT1 signaling pathway.Methods SD rats were randomly divided into 4 groups:Sham group,TBI+NS group,TBI+DEX group and TBI+DEX+EX527 group.The water content of brain tissue after traumatic brain injury was evaluated by dry/wet weight method;the neurological function was evaluated by neurological severity score;the expression of Bcl-2 and Bax proteins in rat cortex were detected by Western blot.Results DEX decreased the expression of apoptosis-promoting regulatory protein Bax(P<0.05),increased the expression of apoptosisinhibiting regulatory protein Bcl-2(P<0.05),alleviated brain edema(P<0.05)and improvedthe neurological function after traumatic brain injury(P<0.05).The changes of the above indexes were reversed by SIRT1 inhibitor EX527.Conclusions DEX can reduce the secondary damage after traumatic brain injury by inhibiting the apoptosis of nerve cells.There may be a certain correlation between the neuroprotective effect and SIRT1 signaling pathway.