昼夜节律紊乱对大鼠颅脑损伤引起的认知衰退和神经损伤的影响

Effect of circadian rhythm disorder on cognitive decline and neurologic impairment after traumatic brain injury in rats

目的探讨昼夜节律紊乱对大鼠创伤性颅脑损伤引起的认知衰退和神经损伤的影响。方法采用自由落体撞击伤法用SD大鼠建立创伤性颅脑损伤模型,大鼠模型根据其生活环境昼夜的长短分为全昼组和对照组。14 d后利用水迷宫试验和跳台试验评价各组大鼠的记忆能力;采用HE染色和Brd U、Ki-67免疫组化评价各组大鼠脑内神经损伤的程度;采用realtime PCR方法分析各组大鼠脑内凋亡相关蛋白Caspase-3、Caspase-9、Bcl-2和Bax的mRNA表达量。结果全昼组大鼠的记忆能力显著弱于对照组,而海马区细胞损伤程度及皮质病灶体积显著高于对照组;全昼组大鼠脑部细胞的增殖速率以及新生细胞的数量显著低于对照组;全昼组大鼠脑内Bcl-2 mRNA水平显著低于对照组,而Caspase-3、Caspase-9和Bax mRNA水平显著高于对照组。结论昼夜节律紊乱能促进大鼠颅脑损伤引起的认知衰退和神经损伤。

Objective To explore the effect of circadian rhythm disorder on cognitive decline and neurologic impairment after traumatic brain injury （TBI） in rats. Methods Rats were subjected to a weight-drop model of TBI, then the rat models were divided into 2 groups ac- cording to the environmental length of day and night, namely, the whole day group （12 h light/12 h light） and the control group（ 12 h light/ 12 h dark）. After 14 days,the Morris water maze test and step-down test were carried out to evaluate the memory of the rats in each group. HE staining and immunohistochemistry （BrdU, Ki-67 ） were carried out to evaluate the degree of the neurologic impairment of the rats in each group. And the mRNA expressions of Caspase-3, Caspase-9, Bcl-2 and Bax were evaluated with reahime PCR. Results The memory function of the rats in whole day group was significant lower than control group ; the damage degree of the cells in the hippocampus and the cortical lesion volume in whole day group were significant higher than control group;the cell proliferation rate and newborn cell survival rate in the whole day group decreased significantly compared with the control group ; the mRNA expression of Bcl-2 in whole day group was signifi- ant lower than control group, and the mRNA expression of Caspase-3, Caspase-9 and Bax in whole day group was signifiant higher than control arouD. Conclusion Circadian rhythm disorder can worsen TBI-induced cognitive decline and neurologie impairment.