川芎嗪对LPS致神经认知障碍的影响及功能影像学评价

Effect of tetramethylpyrazine on neurocognitive impairment and functional imaging changes induced by lipopolysaccharide

目的:探讨中药单体川芎嗪对脂多糖(lipopolysaccharide, LPS)诱导的神经认知障碍的影响及其功能影像学机制。方法:将36只SD大鼠随机分成空白对照组、假手术组、模型组(LPS组)、低剂量川芎嗪组、中剂量川芎嗪组和高剂量川芎嗪组,每组6只。模型组及低剂量、中剂量和高剂量川芎嗪组均行侧脑室注射LPS,每只150μg;假手术组侧脑室注射等量的脑脊液;空白对照组不做处理;低、中和高剂量川芎嗪组分别腹腔注射50 mg/kg、100 mg/kg和200 mg/kg的盐酸川芎嗪注射液。用Morris水迷宫实验观察LPS对神经认知障碍的影响;酶联免疫吸附测定(ELISA)法检测脑组织匀浆中白细胞介素1β(IL-1β)和肿瘤坏死因子α(TNF-α)的含量;同时用影像学扫描IVIM D和IVIM D*功能序列,测定LPS致神经认知障碍的影像学纯水分子的扩散运动成分和血流灌注相关的扩散运动。结果:Morris水迷宫大鼠空间学习和记忆结果显示:与对照组比,模型组的逃避潜伏期延长,平台周边穿梭次数减少,目标象限停留时间缩短(P<0.05);与模型组相比,低剂量川芎嗪组逃避潜伏期缩短,平台周边穿梭次数增加,目标象限停留时间延长(P<0.05),中、高剂量川芎嗪组无显著差异。ELISA结果显示:与对照组比,模型组皮层和海马区的IL-1β和TNF-α均增加(P<0.05);与模型组比,低剂量组皮层和海马区IL-1β和TNF-α均降低(P<0.05),中、高剂量组无显著差异。影像结果显示:与对照组比,模型组皮层和海马的IVIM D、IVIM D*和f值均降低(P<0.05);与模型组比,低剂量组皮层和海马的IVIM D、IVIM D*和f值均升高(P<0.05),中、高剂量组IVIM D、IVIM D*和f值无显著差异。结论:川芎嗪具有减轻LPS所致大鼠神经认知障碍的作用,其机制可能与川芎嗪通过促进脑中水分子扩散运动和脑血流灌注而抑制炎症反应有关。

AIM:To investigate the effect of traditional Chinese medicine tetramethylpyrazine on neurocognitive impairment and functional imaging changes induced by lipopolysaccharide(LPS).METHODS:Sprague-Dawley(SD)rats(n=36)were randomly divided into 6 treatment groups(n=6 for each group):control group,sham operation group,LPS group,and low dose,medium dose and high dose of tetramethylpyrazine groups.The rats in LPS group and tetramethylpyrazine groups were intracerebroventricularly injected with LPS(150μg per rat,dissolved in cerebrospinal fluid),whereas the rats in sham operation group were administered the same volume of cerebrospinal fluid in a similar manner.The rats in low dose group,medium dose group and high dose group were intraperitoneally injected with tetra-methylpyrazine at 50 mg/kg,100 mg/kg and 200 mg/kg,respectively.The neurocognitive impairment was accessed using Morris water maze.The protein levels of interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)were measured by ELISA.The functional imaging changes induced by LPS,including the diffusion motion component of the imaging pure water molecule and the blood perfusion-related diffusion movement,were determined using the imaging IVIM D and IVIM D*functional sequence.RESULTS:In Morris water maze,LPS significantly increased the escape latency,and decreased the number of crossing platform and the time in the target quadrant compared with sham operation group(P<0.05).In addition,low dose of tetramethylpyrazine treatment obviously shortened the escape latency,and increased the number of cros-sing platform and the time in the target quadrant compared with LPS group(P<0.05),but no significant difference between LPS group and medium dose or high dose group was observed.LPS exposure significantly increased IL-1βand TNF-αlevels in the cortex and hippocampus compared with sham operation group(P<0.05),while low dose of tetrame-thylpyrazine treatment obviously attenuated the elevated IL-1βand TNF-αlevels in the cortex and hippocampus induced by LPS(P<0.05).The imaging results showed that LPS exposure significantly decreased the IVIM D,IVIM D*,and f va-lues of the cortex and hippocampus compared with sham operation group(P<0.05),whereas low dose of tetrame-thylpyrazine treatment obviously inhibited the decreases in IVIM D,IVIM D*,and f values induced by LPS(P<0.05).However,no significant difference of the IVIM D,IVIM D*,and f values between LPS group and midium dose or high dose group was found.CONCLUSION:Tetramethylprazine attenuates neurocognitive impairment induced by LPS in the rats.The mechanism may be related to the inhibition of inflammatory response through the increases in the water molecule diffusion and the perfusion of cerebral blood flow in the brain.