归芪聪志汤对血管性痴呆模型大鼠行为学和海马组织基因表达谱的影响

发布时间：2018-04-27 04:08

本文选题：血管性痴呆 + 归芪聪志汤　；参考：《中药新药与临床药理》2017年06期

【摘要】：目的研究归芪聪志汤对血管性痴呆(Vasculardementia,VD)大鼠模型海马基因表达谱的影响及部分筛选基因表达的影响。方法从120只SPF级Wistar雌性大鼠中随机选取10只作为假手术组,其余均采用改良后的两血管阻断法改良法制备血管性痴呆大鼠模型,经水迷宫筛选出合格造模大鼠35只,随机区组分为假手术组,模型组,阳性对照组,归芪聪志汤高、中、低剂量组。归芪聪志汤连续灌胃4周后处死大鼠取材海马组织。Morris水迷宫检测造模后及治疗后行为学变化。全基因组表达谱芯片检测归芪聪志汤中剂量组与模型组海马组织之间差异表达的基因;RT-qPCR检测紧密连接蛋白-1,2,3,14,22(claudin-1,claudin-2,claudin-3,claudin-14,claudin-22),细胞黏附分子(ICAM),血管紧张素转化酶(ACE)的mRNA表达量。结果Morris水迷宫检测显示:模型鼠逃避潜伏期明显延长,跨原平台次数明显减少(P0.01)。治疗28d后模型组逃避潜伏期明显延长,跨原平台次数明显减少(P0.05);与模型组相比,各治疗组大鼠逃逸潜伏期均缩短,跨原平台次数均增多(P0.01),其中归芪聪志汤中剂量组、阳性药物对照组大鼠学习记忆能力改善情况优于归芪聪志汤高、低剂量组(P0.05)。基因芯片和RT-qPCR检测结果显示:与假手术组比较,模型组claudin-1,claudin-2,claudin-3,claudin-22,ICAM,ACE基因表达量均升高(P0.05,P0.01),claudin-14、CDH3基因表达量均下降(P0.05,P0.01);与模型组比较,各治疗组claudin-1,claudin-2,claudin-3,claudin-22,ICAM,ACE基因表达量均下降,claudin-14,CDH3基因表达量均升高,其中,归芪聪志汤中剂量组、阳性药物对照组优于归芪聪志汤高、低剂量组(P0.05)。结论归芪聪志汤能下调VD模型大鼠海马组织claudin-1,claudin-2,claudin-3,claudin-22,ICAM,ACE的表达,并升高claudin-14,CDH3的表达,从而发挥抗VD作用。
[Abstract]:Objective to study the effect of Gui Qi Cong Zhi decoction on gene expression profile of hippocampus and partial screening gene expression in rats with vascular dementia. Methods Ten female SPF Wistar rats were randomly selected as sham-operation group. The other rats were made vascular dementia model by modified two-vessel occlusion method. 35 eligible rats were selected by water maze. The rats were randomly divided into sham-operation group, model group, positive control group and high, middle and low dose groups. The rats were sacrificed after 4 weeks of continuous gavage of Gui Qi Cong Zhi decoction. Morris water maze was used to detect the behavioral changes after model making and after treatment. The differentially expressed genes between the middle dose group and model group of Gui Qi Cong Zhi decoction were detected by RT-qPCR to detect the expression of mRNA in the tight junction protein (-1C ~ (-2), the cell adhesion molecule ICAM, and the angiotensin converting enzyme (ACE-C). The expression of tight junction protein (-1C) was detected by RT qPCR in the middle dose group of Gui Qi Cong Zhi Tang and the model group. The expression of mRNA was detected by RT qPCR in the rat hippocampal tissue of Gui Qi Cong Zhi Tang. Results the Morris water labyrinth test showed that the escape latency of the model rats was prolonged and the frequency of crossing the original platform was significantly decreased (P 0.01). After 28 days of treatment, the escape latency of the model group was significantly prolonged, and the times of crossing the original platform decreased significantly (P 0.05), compared with the model group, the escape latency of the rats in each treatment group was shortened, and the times of crossing the original platform were increased with the increase of P0.01, among which the middle dose group of Gui Qi Cong Zhi decoction. The improvement of learning and memory ability in the positive drug control group was better than that in the Gui Qi Cong Zhi decoction group. The results of microarray and RT-qPCR analysis showed that compared with the sham-operated group, the expression of the ICAMACE gene in the model group was higher than that in the sham-operated group, and the expression of the ICAMAMACE gene in the model group was higher than that in the sham-operated group, and the expression of p0.05p0.05p0.01in the model group was lower than that in the model group, and the expression of the ICACE gene in the model group was lower than that in the model group, and the expression of claudin-14in-14in-14 gene was increased in the model group, and the expression of ICAMACE gene in the model group was lower than that in the model group, and the expression of the ICAMACE gene in the model group was lower than that in the model group, and the expression level of the ICAMACE gene in the model group was significantly lower than that in the model group. In the middle dose group of Gui Qi Cong Zhi decoction, the positive drug control group was superior to the Gui Qi Cong Zhi decoction in high dose and low dose group (P 0.05). Conclusion Gui Qi Cong Zhi Tang can down-regulate the expression of claudin-1 and claudin-2 and claudin-22ICAMN ACE in hippocampus of VD rats, and increase the expression of claudin-14 CDH3, thus play an anti-VD role.
【作者单位】：甘肃中医药大学临床医学院临检基础教研室;甘肃省中药药理与毒理重点实验室;甘肃省中医方药挖掘与创新转化重点实验室甘肃省中药新产品创制工程实验室;甘肃中医药大学附属医院药剂科;
【基金】：甘肃省科技厅创新团队项目(1308RJIA001) 甘肃省中药药理与毒理重点实验室开放课题(ZDSYS-KJ-2015-010) 甘肃省中医方药挖掘与创新转化重点实验室开放课题(ZYFYZH-KJ-2015-005)
【分类号】：R285.5;R-332

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