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中风瘀热方对缺血性脑卒中模型大鼠的干预作用及机制
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李 琬 1, 2* ,刘炳周 ,鞠建明 ,彭蕴茹 ,王 云 (1. 南京中医药大学附属中西医结合医院药剂科,南京
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210028;2.江苏省中医药研究院,南京 210028;3.山东省寿光市人民医院药剂科,山东 寿光 262700)
中图分类号 R285.5;R965 文献标志码 A 文章编号 1001-0408(2023)13-1601-05
DOI 10.6039/j.issn.1001-0408.2023.13.11
摘 要 目的 研究中风瘀热方对缺血性脑卒中模型大鼠的干预作用及机制。方法 将85只大鼠随机分为假手术组(生理盐水,
n=15)、模型对照组(生理盐水,n=18)、尼莫地平片组(阳性对照,10.8 mg/kg,n=18)和中风瘀热方高剂量组(20.52 g/kg,n=17)、
中风瘀热方低剂量组(5.13 g/kg,n=17)。预防性连续给药7 d(每天1次)后,除假手术组外,其余各组均采用改良线栓法制备大鼠
大脑中动脉阻塞(MCAO)模型。造模成功后,各组大鼠继续给药3 d。实验期间,观察大鼠一般情况,进行神经功能评分;末次给
药后,计算脏器指数,观察大鼠脑梗死面积及脑组织病理形态学变化,检测大鼠脑组织及血清中肿瘤坏死因子α(TNF-α)、白细胞
介素6(IL-6)水平及脑组织中胱天蛋白酶3(caspase-3)、磷酸化蛋白激酶B(p-AKT)蛋白的平均光密度值。结果 造模3 d后,与假
手术组比较,模型对照组大鼠神经功能评分,脑指数、脾指数,脑梗死面积占比,脑组织和血清中TNF-α、IL-6水平,脑组织中cas‐
pase-3蛋白平均光密度值均显著升高(P<0.05或P<0.01);脑组织出现核固缩、弥散性水肿等病变。与模型对照组比较,各给药
组上述指标均有不同程度的改善,其中中风瘀热方高剂量组大鼠脑指数、脾指数,脑梗死面积占比,脑组织和血清中TNF-α水平,
脑组织中caspase-3蛋白和p-AKT蛋白的平均光密度值均显著回调(P<0.05或P<0.01)。结论 中风瘀热方对MCAO模型大鼠有
一定的防治作用;其机制可能是通过减少炎症因子TNF-α、IL-6的分泌,下调缺血侧脑组织中caspase-3蛋白表达,上调缺血侧脑组
织中p-AKT蛋白表达,从而达到保护神经元的作用。
关键词 中风瘀热方;缺血性脑卒中;大脑中动脉阻塞模型;胱天蛋白酶3;磷酸化蛋白激酶B;大鼠
Intervention effect and mechanism of Zhongfeng yure decoction on ischemic stroke model rats
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LI Wan ,LIU Bingzhou ,JU Jianming ,PENG Yunru ,WANG Yun (1. Dept. of Pharmacy, the Affiliated
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Hospital of Integrated Traditional Chinese and Western Medicine of Nanjing University of Chinese Medicine,
Nanjing 210028, China;2. Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China;
3. Dept. of Pharmacy, Shouguang Municipal People’s Hospital of Shandong Province, Shandong Shouguang
262700, China)
ABSTRACT OBJECTIVE To study the intervention effect and mechanism of Zhongfeng yure decoction on ischemic stroke
model rats. METHODS Totally 85 rats were randomly divided into sham operation group (normal saline, n=15), model control
group (normal saline, n=18), Nimodipine tablet group (positive control, 10.8 mg/kg, n=18), high-dose group of Zhongfeng
yure decoction (20.52 g/kg, n=17) and low-dose group of Zhongfeng yure decoction (5.13 g/kg, n=17), respectively. After 7
days of preventive continuous administration (once a day), except for the sham operation group, the rats’ middle cerebral artery
occlusion (MCAO) model was established by the modified suture method in other groups. After modeling, the rats in each group
continued to be administered for 3 days. During experiment, general condition of the rats was observed, and the neurological
function score was performed. After the last administration, the organ index was calculated, the cerebral infarction area and
pathological changes of brain tissue were observed. The levels of tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) in brain
tissue and serum, and the average optical density value of caspase-3 and phosphorylated protein kinase B(p-AKT) protein in brain
tissue were detected. RESULTS Three days after modeling, compared with sham operation group, the neurological function score,
in brain tissue index, spleen tissue index, proportion of cerebral infarction area, the levels of TNF-α and IL-6 in brain tissue and
serum, and the average optical density value of caspase-3 protein in brain tissue were significantly increased in the model control
group (P<0.05 or P<0.01); karyopyknosis, diffuse edema and other lesions appeared in brain tissue. Compared with the model
control group, the above indexes in each administration group
Δ 基金项目 江苏省中西医结合医院院内制剂资助项目(No. were improved to varying degrees. Among them, there were
YNZJ1920) significant regression in brain tissue index, spleen tissue
*第一作者 主管中药师。研究方向:中药新产品研发及药效物质
index, proportion of cerebral infarction area, TNF-α level in
基础。E-mail:303692783@qq.com
# 通信作者 主管中药师,硕士。研究方向:中药新剂型、新工艺及 brain tissue and serum, and the average optical density values
中药质量控制。E-mail:632307956@qq.com of caspase-3 protein and p-AKT protein in brain tissue of rats
中国药房 2023年第34卷第13期 China Pharmacy 2023 Vol. 34 No. 13 · 1601 ·