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1.南京中医药大学附属中西医结合医院药剂科,南京 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
主管中药师。研究方向:中药新产品研发及药效物质基础。E-mail:303692783@qq.com
主管中药师,硕士。研究方向:中药新剂型、新工艺及中药质量控制。E-mail:632307956@qq.com
纸质出版日期:2023-07-15,
收稿日期:2023-01-18,
修回日期:2023-03-10,
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李琬,刘炳周,鞠建明等.中风瘀热方对缺血性脑卒中模型大鼠的干预作用及机制 Δ[J].中国药房,2023,34(13):1601-1605.
LI Wan,LIU Bingzhou,JU Jianming,et al.Intervention effect and mechanism of Zhongfeng yure decoction on ischemic stroke model rats[J].ZHONGGUO YAOFANG,2023,34(13):1601-1605.
李琬,刘炳周,鞠建明等.中风瘀热方对缺血性脑卒中模型大鼠的干预作用及机制 Δ[J].中国药房,2023,34(13):1601-1605. DOI: 10.6039/j.issn.1001-0408.2023.13.11.
LI Wan,LIU Bingzhou,JU Jianming,et al.Intervention effect and mechanism of Zhongfeng yure decoction on ischemic stroke model rats[J].ZHONGGUO YAOFANG,2023,34(13):1601-1605. DOI: 10.6039/j.issn.1001-0408.2023.13.11.
目的
2
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
2
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
2
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caspase-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
2
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。
OBJECTIVE
2
To study the intervention effect and mechanism of Zhongfeng yure decoction on ischemic stroke model rats.
METHODS
2
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
2
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 were improved to varying degrees. Among them, there were significant regression in brain tissue index, spleen tissue index, proportion of cerebral infarction area, TNF-α level in brain tissue and serum, and the average optical density values of caspase-3 protein and p-AKT protein in brain tissue of rats in high-dose group of Zhongfeng yure decoction (
P
<0.05 or
P
<0.01).
CONCLUSIONS
2
Zhongfeng yure decoction has a certain intervention and therapeutic effect on MCAO model rats. The mechanism may be to reduce the secretion of inflammatory factors TNF-α and IL-6, down-regulate the expression of caspase-3 protein in ischemic brain tissue, up-regulate the expression of p-AKT protein, so as to protect the neurons.
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
ischemic strokemiddle cerebral artery occlusion modelcaspase-3phosphorylated protein kinase Brats
FARINA M,VIEIRA L E,BUTTARI B,et al. The Nrf2 pathway in ischemic stroke:a review[J]. Molecules,2021,26(16):5001.
王陇德,毛群安,张宗久,等. 我国脑卒中防治仍面临巨大挑战:《中国脑卒中防治报告2018》概要[J]. 中国循环杂志,2019,34(2):105-119.
KADIR R R A,BAYRAKTUTAN U. Urokinase plasminogen activator:a potential thrombolytic agent for ischaemic stroke[J]. Cell Mol Neurobiol,2020,40(3):347-355.
龚杰. 基于KATP通道研究瘀热方对缺血性卒中后NVU的保护作用研究[D]. 南京:南京中医药大学,2021.
承诺. 瘀热方治疗脑梗死后认知功能障碍的临床疗效观察[D]. 南京:南京中医药大学,2022.
陆语迪. 瘀热方通过调控ROS/NLRP3对瘀热阻窍证急性缺血性脑卒中的脑保护作用研究[D]. 南京:南京中医药大学,2021.
王云,李琬,彭蕴茹,等. UPLC-Q-TOF-MS/MS技术结合网络药理学探讨中风瘀热方治疗缺血性脑卒中的作用机制[J]. 中药材,2022,45(12):2905-2911.
缪晓东. 乳香:没药配伍有效部位的制备工艺研究及其对缺血性中风的保护作用[D]. 南京:南京中医药大学,2020.
LEE J Y,CHOI S Y,OH T H,et al. 17β-estradiol inhibits apoptotic cell death of oligodendrocytes by inhibiting RhoA-JNK3 activation after spinal cord injury[J]. Endocrinology,2012,153(8):3815-3827.
卢小叶,吕倩忆,李棋龙,等. Zea-longa评分与改良Garcia评分应用于针刺治疗CIRI大鼠神经功能缺损评估的研究[J]. 湖南中医药大学学报,2021,41(9):1356-1360.
蔡静,黄文静,刘时喜,等. 基于TGF-β1/Smad3信号探讨红景天苷对缺血性脑卒中大鼠的神经保护作用机制[J]. 中草药,2020,51(24):6294-6301.
TRIAS E,BARBEITO L,YAMANAKA K. Phenotypic heterogeneity of astrocytes in motor neuron disease[J]. Clin Exp Neuroimmunol,2018,9(4):225-234.
蔡亮,张炳东. PI3K/AKT信号通路在脑缺血再灌注损伤中的研究进展[J]. 广西医科大学学报,2021,38(10):2012-2016.
陈岩岩,李花,刘旺华,等. 加味四君子汤通过调控Fibulin-5,p-Akt表达抗脑缺血大鼠神经细胞失巢凋亡机制[J]. 中国实验方剂学杂志,2021,27(1):112-120.
NAMIKAWA K,HONMA M,ABE K,et al. Akt/protein kinase B prevents injury-induced motoneuron death and accelerates axonal regeneration[J]. J Neurosci,2000,20(8):2875-2886.
LIU R R,SONG P P,GU X H,et al. Comprehensive landscape of immune infiltration and aberrant pathway activation in ischemic stroke[J]. Front Immunol,2021,12:766724.
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