摘要
目的比较复方丹参片及其拆方对血管性痴呆(VD)模型大鼠的学习记忆能力的改善作用和机制。方法通过穿梭箱筛选出学习记忆能力处于正常范围内的大鼠,随机分为假手术组、模型组、阳性药组(甲磺酸双氢麦角毒碱片0.65 g/kg)、丹参组(丹参乙醇提取物0.3 g/kg)、三七组(三七粉0.3 g/kg)、复方丹参片组(0.3、0.6 g/kg)组,ig给药,每日1次,预防给药7 d后,通过双侧颈总动脉结扎再灌注法制备VD大鼠模型,连续给药7 d后,进行穿梭箱实验和神经功能缺损评分;TTC染色检测脑梗死面积,Nissl染色检测大鼠大脑皮层病理变化;试剂盒法检测脑组织内超氧化物歧化酶(SOD)、丙二醛(MDA)、乙酰胆碱(Ach)、5-羟色胺(5-HT)及血清血管内皮生长因子(VEGF)、内皮素(ET)、内皮型一氧化氮合酶(eNOS)、白细胞介素-6(IL-6)等指标的变化。结果与模型组比较,复方丹参片组可一定程度地提高VD大鼠条件刺激回避次数,降低神经功能损害评分和脑梗死面积,减少大鼠脑组织MDA和血清ET、eNOS和IL-6水平,升高脑组织Ach、5-HT及SOD和血清VEGF水平;拆方研究显示,丹参提取物在减少大鼠脑组织MDA和血清ET、eNOS、IL-6水平,升高脑组织SOD水平方面较三七表现更出色;三七在提高脑组织Ach、5-HT含量方面表现更突出。复方丹参片高剂量组在提高SOD、降低MDA水平,提高Ach、5-HT、VEGF水平等方面优于单方组,与丹参组或三七组比较差异显著(P<0.05、0.01)。结论复方丹参片能够较好地改善VD大鼠的认知学习记忆能力,其作用机制可能是通过增强中枢胆碱能神经系统分泌Ach的功能,提高海马及下丘脑区单胺类神经递质5-HT等的释放,减轻脑组织脂质过氧化损伤,抑制炎性损伤反应和促进血管生成等多条途径实现的。在复方中丹参提取物发挥主要作用,起到君药的作用,三七辅佐君药治疗VD。
Objective To compare the effect and mechanism of Compound Danshen Tablets and its disassembled prescription on learning and memory ability of rats with vascular dementia (VD). Methods Rats with normal learning and memory ability were screened through the shuttle box, and then divided into seven groups:sham group, model group, contrast group (dihydroergotaminemesylate 0.65 g/kg), Danshen group (ethanol extract of Salvia miltiorrhiza 0.3 g/kg), Senqi group (Panax notoginseng powder 0.3 g/kg), Compound Danshen Tablets group (low dose 0.3 g/kg, high dose 0.6 g/kg), ig administration, once daily one time, after 7 d of continuous administration, the VD rat model was established by bilateral common carotid artery ligation and reperfusion. After 7 d of continuous administration, the shuttle box test and neurological deficit score were performed;TTC staining and Nissl staining were used to detect the area of cerebral ischemia and the pathological changes of rat in the cerebral cortex respectively. The changes of SOD, MDA, Ach, 5-HT in the brain and VEGF, ET, eNOS, IL-6 in the serum were detected by kit. Results Compared with the model group, the Compound Danshen Tablets group increased the number of conditional stimulation avoidance in VD rats, reduced the neurological function score and cerebral ischemia area, and reduced the MDA in rat brain tissue and ET, eNOS, IL-6 in rat serum, and increased Ach, 5-HT, SOD in the brain and VEGF in the serum. S. miltiorrhiza extract had better performance in reducing MDA in rat brain tissue and ET, eNOS, IL-6 in rat serum, SOD in the brain than in P. notoginseng;P. notoginseng was more advantageous in improving the content of Ach and 5-HT in rat brain tissue. The high-dose group of Compound Danshen Tablets had significant differences in SOD, MDA, ACH, 5-HT, and VEGF compared with Danshen group or Senqi group (P < 0.05, P < 0.01). Conclusion Compound Danshen Tablets can improve the cognitive learning and memory ability of VD rats. The mechanism maybe enhance the secretion of Ach by the central cholinergic nervous system, improve the content of the monoamine neurotransmitters 5-HT in the hippocampus and hypothalamus, reduce the lipid peroxidation damage of the brain tissue, inhibit the inflammatory injury reaction and promote angiogenesis. In the compound, S. miltiorrhiza extract as the role of "Jun medicine", plays a major role, while P. notoginseng assists "Jun medicine" in treating VD.
作者
梁小娜
林娟
李新
徐旭
王德勤
王玉丽
匡艳辉
李晓霞
黄启和
侯文彬
郭海彪
LIANG Xiao-na;LIN Juan;LI Xin;XU Xu;WANG De-qin;WANG Yu-li;KUANG Yan-hui;LI Xiao-xia;HUANG Qi-he;HOU Wen-bin;GUO Hai-biao(Tianjin University of Traditional Chinese Medicine,Tianjin 300193,China;Tianjin Institute of Pharmaceutical Research,Tianjin 300193,China;Guangzhou Baiyunshan Hutchison Whampoa Chinese Medicine Co.,Ltd.,Guangzhou 510515,China;Tianjin Medical University,Tianjin 300070,China;North China University of Science and Technology,Tangshan 063200,China;State Key Laboratory of Drug Delivery Technology and Pharmacokinetics,Tianjin 300193,China;Tianjin Key Laboratory of Quality Markers for Traditional Chinese Medicine,Tianjin 300193,China)
出处
《中草药》
CAS
CSCD
北大核心
2019年第12期2884-2890,共7页
Chinese Traditional and Herbal Drugs
基金
国家中医药管理局中药标准化项目(ZYBZH-C-GD-05)
