潞党参口服液对慢性脑缺血小鼠脑血流量及认知功能的影响

EFFECTS OF LUDANGSHEN ORAL LIQUID ON CEREBRAL BLOOD FLOW AND COGNITIVE FUNCTION IN MICE WITH CHRONIC CEREBRAL ISCHEMIA

目的观察潞党参口服液对慢性脑缺血(chronic cerebral ischemia,CCI)小鼠脑血流量(cerebral blood flow,CBF)及认知功能的影响。方法将SPF级C57 BL/6 J雄性小鼠按随机数表法分为5组,分别为假手术组、模型组和潞党参口服液4.25 g·kg^(-1)组、潞党参口服液8.5 g·kg^(-1)组、潞党参口服液17 g·kg^(-1)组,每组12只,假手术组只分离相关血管,模型组和给药组复制双侧颈总动脉狭窄(bilateral CCA stenosis,BCAS)模型,假手术组和模型组灌胃生理盐水,给药组灌胃潞党参口服液,连续灌胃30 d。采用激光散斑血流成像系统观察小鼠术前及术后多个时间点(2 h、2 d、4 d、7 d、14 d、30 d)前额叶局部CBF,应用旷场实验、新物体识别实验和Morris水迷宫实验等行为学方法评价认知功能。结果术后小鼠前额叶CBF骤降,以术后2 h最明显,至术后30 d仍低于正常水平,同时小鼠出现认知功能障碍。旷场实验观察到各组之间自主行为差异无统计学意义,相较于假手术组,模型组新物体识别指数降低,差异有统计学意义(P<0.05),逃避潜伏期显著增长,差异有统计学意义(P<0.05),穿过平台次数减少,差异有统计学意义(P<0.05),第Ⅲ象限的时间及路程百分比显著降低,差异有统计学意义(P<0.05)。相较于模型组,潞党参口服液高剂量组新物体识别指数显著升高,差异有统计学意义(P<0.05),潞党参口服液中、高剂量组穿越平台的次数增加,差异有统计学意义(P<0.05),逃避潜伏期降低,差异有统计学意义(P<0.05);潞党参口服液低、中、高剂量组在第Ⅲ象限停留时间及路程百分比明显提高,差异有统计学意义(P<0.05)。结论双侧颈总动脉狭窄法可造成小鼠出现慢性CBF下降进而导致小鼠出现持续性认知功能障碍;潞党参口服液能够增加CCI小鼠局部CBF,改善认知功能,且具有量效关系。

Objective To observe the effect of Ludangshen Oral Liquid on cerebral blood flow(CBF)and cognitive function in mice with chronic cerebral ischemia(CCI).Methods SPF C57 BL/6 J male mice were randomly divided into 5 groups:sham operation group,model group and Ludangshen oral liquid 4.25 g·kg^(-1),Ludangshen oral liquid 8.5 g·kg^(-1),Ludangshen oral liquid 17 g·kg^(-1),with 12 mice in each group.The sham operation group only separated related blood vessels,the model group and the drug administration group copied bilateral common carotid artery stenosis(BCAS)models.The sham operation group and the model group were gavaged with normal saline.The administration group was given Ludangshen oral liquid by gavage for 30 days.Laser speckle flow imaging system was used to observe the local CBF in the prefrontal lobe of mice at various time points(2 h,2 d,4 d,7 d,14 d,30 d)before and after operation.The open field experiment,new object recognition experiment and Morris water maze experiment were used to evaluate cognition function.Results The CBF in the prefrontal lobe of the mice dropped sharply after operation,which was most obvious 2 hours after operation,and was still lower than the normal level30 days after operation.At the same time,the mice had cognitive dysfunction.Open field experiment showed that there was no difference in autonomous behavior among the groups.Compared with the sham operation group,the new object recognition index of the model group decreased,with a statistically significant difference(P<0.05),the escape latency increased significantly,the difference was statistically significant(P<0.05),the number of times crossing the platform decreased,the difference was statistically significant(P<0.05),and the time and distance percentage of the third quadrant decreased significantly,the difference was statistically significant(P<0.05).Compared with the model group,the new object recognition index in the high-dose group of Ludangshen oral liquid significantly increased(P<0.05),the times of crossing the platform in the middle and highdose groups of Ludangshen oral liquid increased,with a statistically significant difference(P<0.05),and the escape latency decreased,with a statistically significant difference(P<0.05).The retention time and distance percentage in the third quadrant of the low,middle and high dose groups of Ludangshen oral liquid were significantly increased(P<0.05).Conclusions Bilateral common carotid artery stenosis can cause chronic decrease of CBF in mice and lead to persistent cognitive impairment in mice.Ludangshen Oral Liquid can increase local CBF and improve cognitive function in CCI mice in a dose-dependent manner.