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北京中医药大学,北京 100029
孙晓丽,博士,从事中西医结合血管相关疾病、中药新药研究,E-mail:xiaolisun321@126.com
王伟,博士,教授,博士生导师,从事中西医结合心血管临床与药理学、证候生物学基础研究及血管性疾病中药新药研发,Tel:010-64286283;E-mail:wangwei26960@126.com
纸质出版日期:2019-12-20,
网络出版日期:2019-09-05,
收稿日期:2019-05-21,
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孙晓丽, 王勇, 刘俊杰, 等. 龙生蛭胶囊对脑卒中大鼠行为学的影响及脑组织的保护作用[J]. 中国实验方剂学杂志, 2019,25(24):23-29.
Xiao-li SUN, Yong WANG, Jun-jie LIU, et al. Effect of Longshengzhi Capsule on Behavior and Cerebral Protection in Stroke Rats[J]. Chinese Journal of Experimental Traditional Medical Formulae, 2019,25(24):23-29.
孙晓丽, 王勇, 刘俊杰, 等. 龙生蛭胶囊对脑卒中大鼠行为学的影响及脑组织的保护作用[J]. 中国实验方剂学杂志, 2019,25(24):23-29. DOI: 10.13422/j.cnki.syfjx.20192403.
Xiao-li SUN, Yong WANG, Jun-jie LIU, et al. Effect of Longshengzhi Capsule on Behavior and Cerebral Protection in Stroke Rats[J]. Chinese Journal of Experimental Traditional Medical Formulae, 2019,25(24):23-29. DOI: 10.13422/j.cnki.syfjx.20192403.
目的:
2
评价龙生蛭胶囊对脑卒中大鼠行为学影响及其对血清生化学和核转录因子-
κ
B(NF-
κ
B)和半胱氨酸的天冬氨酸蛋白水解酶-3(Caspase-3)的影响。
方法:
2
采用健康雄性SD大鼠,采用单侧大脑中动脉永久性结扎手术(pMCAO),将模型制备成功大鼠随机分为模型组,尼莫地平组(12 mg·kg
-1
),龙生蛭胶囊高、中、低剂量组(2.4,1.2,0.6 g·kg
-1
),同时设置假手术组。连续灌胃给药14 d,分别对大鼠神经缺陷功能进行评分并观察期行为学;实验结束,腹主动脉取血,考察血清超氧化物歧化酶(SOD),一氧化氮(NO)和丙二醛(MDA)的变化;解剖取脑组织进行2,3,5-氯化三苯基四氮唑(TTC)染色观察龙生蛭胶囊对脑梗死体积变化,并测定龙生蛭胶囊对脑含水量测定影响;苏木素-伊红(HE)染色观察梗死侧脑组织病理变化;采用蛋白免疫印迹法(Western blot)和免疫组化检测梗死侧脑组织NF-
κ
B和Caspase-3的表达情况。
结果:
2
与假手术比较,模型组神经功能评分显著升高(
P
<
0.01),旋转耐受,抓力明显降低(
P
<
0.01),脑含水量及梗死体积显著升高(
P
<
0.01),SOD活力显著降低(
P
<
0.01),NO和MDA含量显著升高(
P
<
0.01),脑组织中NF-
κ
B以及Caspase-3表达显著升高(
P
<
0.01)。与模型组比较,龙生蛭胶囊能够显著降低神经功能缺陷行为学评分(
P
<
0.05);提高大鼠旋转耐受力,大鼠抓力并提高大鼠自主活动能力;与模型组比较,各给药组能够明显降低脑水含量以及脑梗死体积(
P
<
0.05,
P
<
0.01);能够明显提高血清中SOD活性(
P
<
0.01),降低NO和MDA含量(
P
<
0.05)。能够明显降低脑卒中大鼠脑组织病理损伤,抑制NF-
κ
B以及Caspase-3的表达。
结论:
2
龙生蛭胶囊能够改善大鼠的神经功能缺陷,提高大鼠的肌力和自主运动能力,其对脑组织的保护作用可能与抗氧化,抑制NF-
κ
B以及Caspase-3的表达有关。
Objective:
2
To investigate the effect of Longshengzhi capsule (LSZC) on behavior
serum biochemical index
nuclear transcription factor-
κ
B(NF-
κ
B) and cysteine aspartate-specific protease-3(Caspase-3) in stroke rats.
Method:
2
Ischaemic stroke was induced by the permanent middle cerebral artery occlusion (pMCAO). The male sprague-dawley rats with successful pMCAO modeling were randomly divided into five groups: model (pMCAO) group
nimodipine (12 mg·kg
-1
) group and LSZC groups (2.4
1.2
0.6 g·kg
-1
). A sham group also set in the study. The intragastric administration lasted for 14 days. The rats were tested for neurological deficits
grip strength
rotation tolerance. An open field test was also performed to evaluate the behavior. The pathology of the brain was studied by 2
3
5-triphenyltetrazolium chloride (TTC) staining
and hematoxylin and eosin (HE) staining. In addition
the levels of malondialdehyde (MDA)
nitric oxide (NO) and superoxide dismutase (SOD) in rat serum were tested in the experiment. Immunohistochemistry (ICH) and Western blot were used to analyze the expressions of Caspase-3 and NF-
κ
B.
Result:
2
Compared the model group
LSZC significantly improved the grip strength
rotation tolerance and spontaneous activity. LSZC markedly reduced infarct volume
water content of brain
neurological scores
body weight decline in MCAO stroke rats (
P
<
0.05
P
<
0.01). LSZC significantly decreased the levels of NO and MDA
but increased SOD activity (
P
<
0.05
P
<
0.01). LSZC recovered neuronal morphologic damage in MCAO rats
and down-regulated the expressions of Caspase-3 and NF-
κ
B.
Conclusion:
2
LSZC treatment can improve neurological deficit function and protect the brain of stroke rats. This effect may be realized by down-regulating the expressions of NF-
κ
B and Caspase-3.
龙生蛭胶囊脑卒中脑保护核转录因子-κB(NF-κB)半胱氨酸的天冬氨酸蛋白水解酶-3(Caspase-3)
Longshengzhi capsulestrokecerebral protectionnuclear transcription factor-κB(NF-κB)cysteine aspartate-specific protease-3(Caspase-3)
Hankey G J. Stroke [J].Lancet, 2017, 389: 641-654.
Jauch E C, Saver J L, Adams H P J, et al. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association [J].Stroke, 2013, 44: 870-947.
Balakrishnan R, Kaplan B, Negron R, et al. Life after stroke in an urban minority population: a photovoice project [J].Int J Environ Res Public Health, 2017, 14(3): E293.
王美娟,潘雪薇,张媛媛,等.中药治疗出血性脑卒中的研究进展[J].中国实验方剂学杂志,2019,25(17):226-234.
Rahme R, Curry R, Kleindorfer D, et al. How often are patients with ischemic stroke eligible for decompressive hemicraniectomy? [J].Stroke, 2012, 43: 550-552.
符青伟.步长龙生蛭联合西药治疗缺血性脑卒中随机平行对照研究[J].实用中医内科杂志,2014,28(2):92-94.
许灵花.步长龙生蛭治疗缺血性脑卒中148例[J].中医临床研究,2011,3(16):78.
杨桂林.联合应用龙生蛭胶囊和阿司匹林治疗短暂性脑缺血发作的效果分析[J].当代医药论丛,2015,13(3):168.
Longa E Z, Weinstein P R, Carlson S, et al. Reversible middle cerebral artery occlusion without craniectomy in rats [J].Stroke, 1989, 20: 84-91.
SHI Q J, WANG H, LIU Z X, et al. HAMI 3379, a CysLT2R antagonist, dose-and time-dependently attenuates brain injury and inhibits microglial in ammation after focal cerebral ischemia in rats [J].Neuroscience, 2015, 291: 53-69.
ZHAO B, SHI Q J, ZHANG Z Z, et al. Protective effects of paeonol on subacute/chronic brain injury during cerebral ischemia in rats [J].Exp Ther Med, 2018, 15(4): 3836-3846.
卢文丹,李莉,申艳佳,等.基于血管舒缩相关GPCR靶点的小续命汤网络药理学研究[J].中国中药杂志,2018,43(23):4698-4708.
Kario K. Disaster hypertension-Its characteristics, mechanisms, and management [J].Circ J, 2012, 76(3): 553-562.
曾莉,张旻,卜碧涛,等.实验啮齿类动物行为学评估[J].神经损伤与功能重建,2008,3(5):352-356.
于栋华,刘树民,董培良,等.山精胶囊对心肌缺血大鼠NF-κB信号通路相关凋亡蛋白表达的影响[J].中国实验方剂学杂志,2015,21(11):141-145.
胡跃强,秦红玲,唐农,等.基于Nrf2/ARE信号通路探讨清热化瘀方对大鼠脑缺血再灌注损伤氧化应激反应的影响[J].中国实验方剂学杂志,2018,24(14):128-133.
Madzhidova E N, Usmanova D D, Baǐtursunova Z M. Dynamics of the symptoms of chronic ischemia during the treatment with cytoflavin [J].Zh Nevrol Psikhiatr Im S S Korsakova, 2012, 112 (9): 57-62.
Moskowitz M A, Lo E H, Iadecola C. The science of stroke: mechanisms in search of treatments [J].Neuron, 2010, 67: 181-198.
Jablonska A, Lukomska B. Stroke induced brain changes: implications for stem cell transplantation [J].Acta Neuro biol Exp (Wars), 2011, 7: 74-85.
Aspreet K, Sarika A, Bhawna S, et al. Role of oxidative stress in pathophysiology of transient ischemic attack and stroke [J].Int J Biol Med Res, 2001, 2: 611-615.
Permpoonputtana K, Govitrapong P. The anti-inflammatory effect of melatonin on methamphetamineinduced proinflammatory mediators in human neuroblastoma dopamine SH-SY5Y cell lines [J].Neurotox Res, 2013, 23: 189-199.
HAN J, HIANG M, JIANG X, et al. Epigallocatechin gallate protects against cerebral ischemia-induced oxidative stress via Nrf2/ARE signaling [J].Neurochem Res, 2014, 39: 1292-1299.
王小青,高杨,马帅,等.肾蕨对乙酸致小鼠肛门溃疡的作用及NF-κB,TNF-α,IL-1β和COX-2表达的影响[J].中国实验方剂学杂志,2018,24(8):122-127.
邢清敏,陆曙,周永华,等.生脉散对DCM大鼠的干预作用及对TLR-4/NF-κB炎症信号通路的影响[J].中国实验方剂学杂志,2018,24(2):128-134.
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