黄芩苷对脑小血管病大鼠认知功能的影响及机制  

Effect and mechanism of baicalin on cognitive function in rats with cerebral small vessel disease

作　　者：刘感哲 经屏[1] Liu Ganzhe;Jing Ping(Department of Neurology,Wuhan Central Hospital,Wuhan 430014,Hubei Province,China)

机构地区：[1]武汉市中心医院神经内科,430014

出　　处：《中华老年心脑血管病杂志》2022年第8期802-806,共5页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：武汉市卫生健康委员会资助项目(WX19C03)。

摘　　要：目的探讨黄芩苷(Baicalin)对脑小血管病(CSVD)大鼠认知功能及神经细胞凋亡的影响及其机制。方法将50只CSVD模型大鼠分为假手术组、模型组、黄芩苷组(100 mg/kg黄芩)、抑制剂组[脑源性神经生长因子(BDNF)/酪氨酸激酶受体B(TrkB)信号通路抑制剂K252a 1μg]、联合组(100 mg/kg黄芩+K252a 1μg),每组10只。采用免疫组织化学检测海马组织BDNF表达;Western blot检测海马组织BDNF、B淋巴细胞瘤2(Bcl-2)、Bcl-2相关x蛋白(Bax)、天冬氨酸半胱氨酸蛋白酶3(Caspase-3)蛋白表达和TrkB、磷脂酰肌醇3激酶(PI3K)、蛋白激酶B(Akt)磷酸化水平。结果与假手术组比较,模型组海马组织神经细胞凋亡率明显增加[(26.37±4.41)%vs(6.23±1.23)%,P<0.05]。与模型组比较,黄芩苷组海马组织神经细胞凋亡率明显降低[(11.83±3.76)%vs(26.37±4.41)%],BDNF(0.95±0.08 vs 0.51±0.04)、p-TrkB/TrkB(0.85±0.07 vs 0.37±0.04)、p-PI3K/PI3K(0.83±0.07 vs 0.40±0.05)、p-Akt/Akt(0.76±0.08 vs 0.29±0.04)增加(P<0.05)。与抑制剂组比较,联合组大鼠逃避潜伏期、空间探索时间显著缩短,穿越平台次数显著增加,细胞凋亡率、海马组织Bax、Caspase-3表达水平显著降低,Bcl-2、BDNF、p-TrkB/TrkB、p-PI3K/PI3K、p-Akt/Akt水平显著升高(P<0.05)。结论黄芩苷可改善CSVD大鼠认知功能障碍和降低海马组织神经细胞凋亡,其机制可能与激活BDNF/TrkB/PI3K信号通路有关。Objective To determine the effects of baicalin on cognitive function and neuronal apoptosis in rats with cerebral small vessel disease(CSVD)and investigate the underlying mechanism.Methods The rat model of CSVD was inflicted by bilateral carotid artery ligation.50 SD rats were divided into sham operation group,model group,baicalin group(100 mg/kg baicalin),inhibitor group(1μg K252a,inhibitor of BDNF/TrkB signaling pathway),and combination group(100 mg/kg baicalin+1μg K252a,n=10).Immunohistochemical assay was performed to detect the expression of BDNF in the hippocampus.Western blotting was applied to detect the expression of BDNF,B cell lymphocyte 2(Bcl-2)and its associated X protein(Bax)and Caspase-3,and the phosphorylation levels of TrkB,phosphatidylinositol-3 kinase(PI3K),and protein kinase B(Akt)in the hippocampus.Results The neuronal apoptotic rate was significantly higher in the hippocampus of the model group than the sham operation group[(26.37±4.41)%vs(6.23±1.23)%,P<0.05].Baicalin treatment resulted in obviously lower neuronal apoptotic rate[(11.83±3.76)%vs(26.37±4.41)%],and enhanced protein levels of BDNF(0.95±0.08 vs 0.51±0.04),p-TrkB/TrkB(0.85±0.07 vs 0.37±0.04),p-PI3K/PI3K(0.83±0.07 vs 0.40±0.05),and p-Akt/Akt(0.76±0.08 vs 0.29±0.04)when compared with the model group(P<0.05).While compared with the inhibitor group,the combination group had shorter escape latency and space exploration time,increased times of platform crossing,reduced apoptotic rate,de-creased expression levels of Bax and Caspase-3,and increased levels of Bcl-2,BDNF,p-TrkB/TrkB,p-PI3K/PI3K and p-Akt/Akt in the hippocampus(P<0.05).Conclusion Baicalin can im-prove cognitive dysfunction and reduce neuronal apoptosis in the hippocampus of CSVD rats,and its mechanism may be related to the activation of BDNF/TrkB/PI3K signaling pathway.

关 键 词：黄芩甙 大脑小血管疾病 认知 受体蛋白质酪氨酸激酶类 

分 类 号：R285.5[医药卫生—中药学]