摘要
目的观察滋肾活血方对血管性痴呆(VD)大鼠BDNF/TrkB/PI3K/Akt信号通路的影响,探讨其可能的作用机制。方法采用改良的双侧颈总动脉结扎法(2-VO法)建立大鼠VD模型,将大鼠随机分为假手术组、模型组、滋肾活血低剂量组、滋肾活血高剂量组和奥拉西坦组,每组8只。给药28 d后,HE染色观察大鼠海马组织CA1区变化,免疫组化和Western blot分别检测大鼠脑组织p-Akt、Akt、TrkB和BDNF蛋白的表达。结果HE染色结果:与假手术组比较,模型组大鼠海马组织CA1区损伤较严重,细胞核破裂,胞质浓缩,胞体变小;与模型组比较,滋肾活血低剂量组、滋肾活血高剂量组和奥拉西坦组大鼠海马组织CA1区损伤均明显减轻;免疫组化染色结果:与假手术组比较,模型组大鼠脑组织p-Akt和Akt蛋白表达均明显升高(P<0.05),TrkB和BDNF蛋白表达均明显降低(P<0.05);与模型组比较,滋肾活血低剂量组、滋肾活血高剂量组和奥拉西坦组大鼠脑组织p-Akt和Akt蛋白表达均明显降低(P<0.05),TrkB和BDNF蛋白表达均明显升高(P<0.05);Western blot检测结果:与假手术组比较,模型组大鼠脑组织p-Akt蛋白表达显著升高(P<0.05),TrkB和BDNF蛋白表达均明显降低(P<0.05);与模型组比较,滋肾活血低剂量组、滋肾活血高剂量组和奥拉西坦组大鼠脑组织p-Akt蛋白表达均明显降低(P<0.05),TrkB和BDNF蛋白表达均明显升高(P<0.05)。结论滋肾活血方可提高VD大鼠学习记忆能力,其机制可能与下调VD大鼠脑组织p-Akt、Akt和上调TrkB、BDNF蛋白的表达有关。
Objective To explore the effects of Zishen Huoxue Prescription on BDNF/TrkB/PI3K/Akt signal pathways in vascular dementia(VD)rats;To discuss its possible mechanism.Methods The modified bilateral common carotid artery ligation method(2-VO method)was used to establish rat VD models,and the rats were randomly divided into sham-operation group,model group,Zishen Huoxue low-,high-dosage groups,and Oxiracetam group,with 8 rats in each group.28 days after administration,HE staining was used to observe the changes in the CA1 region of rat hippocampus.Immunohistochemistry and Western blot were used to detect the protein expressions of p-Akt,Akt,TrkB and BDNF in the rat brain.Results The HE results showed that compared with the sham-operation group,the hippocampal CA1 region of the model group was more severely damaged,the nucleus was ruptured,the cytoplasm was concentrated,and the cell body became smaller;compared with the model group,the damage of hippocampal CA1 area was significantly reduced in Zishen Huoxue low-,high-dosage groups,and Oxiracetam group.Immunohistochemical staining results showed that compared with the sham-operation group,the p-Akt and Akt protein expressions in the model group significantly increased(P<0.05),and the TrkB and BDNF protein expressions were significantly reduced(P<0.05);compared with the model group,the expressions of p-Akt and Akt in Zishen Huoxue low-,high-dosage groups,and Oxiracetam group were all reduced(P<0.05),and TrkB and BDNF protein expression significantly increased(P<0.05).Western blot results showed that compared with the sham-operation group,the expression level of p-Akt protein in the model group significantly increased(P<0.05)and TrkB and BDNF protein expression significantly decreased(P<0.05);compared with the model group,the expressions of p-Akt and Akt in Zishen Huoxue low-,high-dosage groups,and Oxiracetam group were all reduced(P<0.05),and TrkB and BDNF protein expression significantly increased(P<0.05).Conclusion Zishen Huoxue Prescription can improve the learning and memory abilities of VD rats.The mechanism may be related to the down-regulation of p-Akt and Akt protein expressions and the up-regulation of TrkB and BDNF protein expressions.
作者
张发友
伍大华
葛金文
刘春华
谢瑶
邓毫斌
周卫强
ZHANG Fayou;WU Dahua;GE Jinwen;LIU Chunhua;XIE Yao;DENG Haobin;ZHOU Weiqiang(Hunan University of Chinese Medicine,Changsha 410208,China;Affiliated Hospital of Hunan Academy of Chinese Medicine,Changsha 410006,China)
出处
《中国中医药信息杂志》
CAS
CSCD
2020年第10期42-47,共6页
Chinese Journal of Information on Traditional Chinese Medicine
基金
国家自然科学基金(81894462)。
关键词
滋肾活血方
血管性痴呆
蛋白激酶
脑源性神经营养因子
大鼠
Zishen Huoxue Prescription
vascular dementia
protein kinase
brain-derived neurotrophic factor
rats
