开心解郁方对慢性脑白质损害大鼠中枢神经系统免疫激活的抑制作用

Inhibition of Kaixin Jieyu Prescription on Immune Activation of Central Nervous System in Rat Chronic Cerebral White Matter Lesion Model

目的:研究开心解郁方对慢性脑白质损害大鼠认知功能、局部脑血流(rCBF)、额叶脑组织中前炎症细胞因子和脂质过氧化的作用,为培元开郁法治疗血管性抑郁症提供科学依据。方法:双侧颈总动脉结扎(LBCCA)制备慢性脑白质损害模型,分别在术后3,7,21 d,采用水迷宫法测定认知功能,激光多普勒血流仪测定rCBF,液相芯片技术测定额叶组织白介素-6(IL-6)、白介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)蛋白含量,黄嘌呤氧化酶法测定超氧化物歧化酶(SOD)活力,硫代巴比妥酸法测定丙二醛(MDA)含量。结果:与假手术组比较,模型组大鼠术后3 d额叶IL-1β、IL-6显著升高(P<0.05或0.001),水迷宫逃避潜伏期显著延长(P<0.05),额叶和顶叶皮质rCBF显著降低(P<0.05);术后7 d额叶IL-1β显著升高(P<0.05);术后21 d额叶MDA含量显著升高(P<0.05)。与模型组比较,开心解郁方组大鼠术后3 d额叶IL-6含量显著降低(P<0.01);术后7 d额叶皮质rCBF显著升高(P<0.01);术后21 d额叶IL-1β和MDA含量显著降低(P<0.001或0.01)。开心解郁方对大鼠认知功能和额叶组织SOD活力无显著影响。结论:开心解郁方对慢性脑白质损害的作用可能与改善脑缺血、抑制中枢神经系统脂质过氧化和免疫过度激活引起的前炎症细胞因子异常升高有关。

Objective： Chronic cerebral white matter lesion is a major pathogenesis factor for vascular depression and one of the keys of development and prediction of vascular depression. The aim of the present study was to explore the action mechanisms of Kaixin Jieyu prescription in rat model of chronic cerebral white matter lesion. Method： 150 male Sprague-Dawley rats were divided into shamoperative group, model control group and Kaixin Jieyu Prescription group, respectively. The rat chronic cerebral white matter lesion model was established by ligation of bilateral common carotid arteries （LBCCA）. Morris water maze performance for cognition was tested before and 3,7 and 21 days after LBCCA,respectively. Regional cerebral blood flow （rCBF） was performed before euthanasia. Markers of antioxidant capacity such as superoxide dismutase （SOD）, malondialchehyche （MDA） in frontal lobe, and the pro-inflammatory markers IL-6,IL-115 and TNF-α were determined in frontal lobe at days 3,7 and 21 after LBCCA,respectively. Result： The IL-1β in rats of chronic cerebral white matter lesion increased at days 3 and 7 after LBCCA （P 〈 0. 05）, IL-6 increased at day 3 after LBCCA （P 〈 0. 001 ） and MDA increased at day 21 after LBCCA （P 〈 0.05 ） compared with those of sham-operative animals. The rCBF of frontal and parietal lobe in rats of chronic cerebral white matter lesion decreased at day 3 after LBCCA （ P 〈 0. 05 ） compared with that of sham-operative animals. It was reversed by Kaixin Jieyu pescription in rCBF at day 7 after LBCCA （P 〈 0. 01 ）, IL-6 at day 3 after LB- CCA （P 〈0. 01 ） ,IL-1β at day 21 after LBCCA （P 〈0. 01 ） and MDA at day 21 after LBCCA （P 〈0. 01 ）. There were no significant differences in cognition tested by Morris water maze and SOD activity in frontal lobe between Kaixin Jieyu prescription-treated animals and model animals at days 3,7 and 21 after LBCCA,respectively. Conclusion： Our data provided new evidence for the hypothesis that the mechanism of Kaixin Jieyu prescription in chronic cerebral white matter lesion mediated by the chronic cerebral hypoperfusion,and pro-inflammatory cytokines resulting from immune activation and oxidative defense.