Effect of Naoxueshu Oral Liquid on the expression of ZO-1 and AQP4 proteins in rat model of intracerebral hemorrhage
WANG Xiaofeng1 TIAN Chao1 ZHANG Yan2 YUAN Mengchen1 ZHANG Hanlai1 WANG Liqin1 AN Na1 GAO Yonghong1
1.Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing 100700, China;
2.Department of Neurosurgery, the Seventh Medical Center of Chinese People′s Liberation Army General Hospital, Beijing 100700, China
Abstract：Objective To observe the effect of Naoxueshu Oral Liquid on the expression of zonula occludens 1 (ZO-1), aquaporin-4 (AQP4) in brain of model rats with intracerebral hemorrhage. Methods A model of intracerebral hemorrhage was produced by injection of collagenase Ⅶ into the caudatum of rats. Healthy male SD rats of SPF grade (8 weeks) were divided into three groups by random number table: the sham group, the model group and the Naoxueshu group, with 8 rats in each group. Naoxueshu Oral Liquid was administrated intragastrically by 0.27 mL/(100 g·d), while saline was administrated to the sham group and model group by the same way. The histopathological change of brain tissue was tested by HE staining and transmission electron microscopy on the 7 d after intracerebral hemorrhage. The expression of ZO-1 and AQP4 in perihematoma tissue was detected by Western blot. Results Compared with the sham group, HE staining showed that large necrosis in perihematomal and the cells were irregular, loose, swollen, and the nuclear structure was unclear and undistinguishable in the 7-day model group. Transmission electron microscopy revealed that the gap between cerebral blood vessels and surrounding tissues was widened, and vacuolar changes were observed, and the astrocyte podocyte edema was obvious. The expression of ZO-1 protein in the brain tissue of the 7-day model group was decreased and AQP4 protein was increased (P ＜ 0.05). Compared with the model group, the pathological structure of the cerebral blood group was significantly improved, and the expression of ZO-1 protein was significantly increased, while the expression of AQP4 protein was significantly decreased (P ＜ 0.05). Conclusion Naoxueshu Oral Liquid can effectively increase the expression of ZO-1 protein and inhibit the expression of AQP4 protein, thereby reduce the permeability of blood-brain barrier and relieve encephaledema, and play a protective role in brain of model rats with intracerebral hemorrhage.
王晓峰1 田超1 张岩2 袁梦晨1 张涵莱1 王丽琴1 安娜1 高永红1. 脑血疏口服液对脑出血模型大鼠脑组织ZO-1和AQP4表达的影响[J]. 中国医药导报, 2019, 16(16): 8-12.
WANG Xiaofeng1 TIAN Chao1 ZHANG Yan2 YUAN Mengchen1 ZHANG Hanlai1 WANG Liqin1 AN Na1 GAO Yonghong1. Effect of Naoxueshu Oral Liquid on the expression of ZO-1 and AQP4 proteins in rat model of intracerebral hemorrhage. 中国医药导报, 2019, 16(16): 8-12.
[1] Lee SH，Park KJ，Park DH， et al. Factors associated with clinical outcomes in patients with primary intraventricular hemorrhage [J]. Med Sci Monit，2017，23：1401-1412.
[2] Fu GL，Wang H，Cai YL，et al. Theaflavin alleviates inflammatory response and brain injury induced by cerebral hemorrhage via inhibiting the nuclear transcription factor kappa β-related pathway in rats [J]. Drug Des Devel Ther，2018，12：1609-1619.
[3] Zhang WQ，Cui Y，Gao JL，et al. Recombinant Osteopontin Improves Neurological Functional Recovery and Protects Against Apoptosis via PI3K/Akt/GSK-3β Pathway Following Intracerebral Hemorrhage [J]. Med Sci Monit，2018， 24：1588-1596.
[4] 潘超，唐洲平.脑出血研究进展：中国学者海外报道[J].中国现代神经疾病杂志，2018，18（11）：770-773.
[5] Aronowski J，Zhao X. Molecular pathophysiology of cerebral hemorrhage：secondary brain injury [J]. Stroke，2011， 42（6）：1781-1786.
[6] 许楠，曹非.脑出血后血脑屏障损害研究进展[J].中国卒中杂志，2015，10（2）：181-186.
[7] 曹冰清，谢瑱，雷琦，等.脑血疏口服液对脑出血后脑水肿的影响及可能机制分析[J].中西医结合心脑血管病杂志，2017，15（21）：2759-2762.
[8] Song J，Lyu Y，Wang P，et al. Treatment of Naoxueshu Promotes Improvement of Hematoma Absorption and Neurological Function in Acute Intracerebral Hemorrhage Patients [J]. Front Physiol，2018，9：933.
[9] Wu L，Li Y，Wang X，et al. A Systematic Review and Meta-Analysis on the Treatment of Cerebral Hemorrhage with NaoXueShu Oral Liquid [J]. Biomed Res Int，2017，2017：8542576.
[10] Longa EZ，Weinstein PR，Carison S，et al. Reversible middle cerebral artery occlusion without craniectomy in rats [J]. Stroke，1989，20（1）：84-91.
[11] Banks WA，Gray AM，Erickson MA，et al. Lipopolysaccharide-induced blood-brain barrier disruption：roles of cyclooxygenase，oxidative stress，neuroinflammation，and elements of the neurovascular unit [J]. J Neuroinflammation，2015，25（12）：223-229.
[12] Han X，Sun S，Zhao M，et al. Celastrol stimulates hypoxia-inducible factor-1 activity in tumor cells by initiating the ROS/Akt/P70S6K signaling pathway and enhanceing hypoxia-inducible factor-1 protein synthesis [J]. PLoS One，2014，11（3）：24-28.
[13] Tso MK，MacDonald RL. Subarachnoid hemorrhage：a review of experimental studies on the microcirculation and the neurovascular unit [J]. Transl Stroke Res，2014，5（2）：174-189.
[14] 张营，刘涛，于荣，等.脑血疏对大鼠脑出血的行为学及凝血功能的影响[J].首都医科大学学报，2017，38（6）：841-845.
[15] 谢道珍，李静，罗林，等.脑血疏通口服液治疗出血性中风的实验研究[J].中国中西医结合杂志，1995，15（S1）：354-357.
[16] 张亚红，刘重霄，周任，等.大鼠脑出血模型中血脑屏障开放规律及应用脑血疏口服液治疗脑水肿的实验研究[J].中西医结合心脑血管病杂志，2016，14（14）：1613-1615.
[17] 蒋锋，袁婕，崔小丽，等.脑血疏口服液对大鼠脑缺血再灌注损伤后血脑屏障的影响[J].卒中与神经疾病，2017， 24（5）：423-426.
[18] Abbott NJ，Patabendige AA，Dolman DE，et al. Structure and function of the blood-brain barrier [J]. Neurobiol Dis，2010，37（1）：13-25.
[19] 王哲，王彦凯，冯伟，等.脑出血后血脑屏障损伤机制的研究进展[J].分子影像学杂志，2016，39（4）：420-424.
[20] 任思颖，伍国锋，杨勤，等.病灶区灌注罗格列酮对脑出血家兔血肿周围咬合蛋白和闭合小环蛋白1mRNA表达水平及血脑屏障通透性的影响[J].中国脑血管病杂志，2017，14（11）：580-584.
[21] Zhang ZY，Sun BL，Yang MF，et al. Carnosine attenuates early brain injury through its antioxidative and anti-apoptotic effects in a rat experimental subarachnoid hemorrhage model [J]. Cell Mol Neurobiol，2015，35（2）：147-157.
[22] Zhang X，Banerjee A，Banks WA，et al. N-acetyl amide protects against methamphetamine-induced oxidative stress and neurotoxicity in immortalized human brain endothelial cells [J]. Brain Res，2009，12（7）：87-95.
[23] Tajes M，Ramos-Fernández E，Weng-Jiang X，et al. The blood-brain barrier：structure，function and therapeutic approaches to cross it [J]. Mol Membr Biol，2014，31（5）：152-167.
[24] 毛剑，邹永杰，巢少辉.水通道蛋白4与脑水肿的研究进展[J].医学综述，2014，20（22）：4061-4063.
[25] Chu H，Huang C，Ding H，et al. Aquaporin-4 and Cerebrovascular Diseases [J]. Int J Mol Sci，2016，17（8）. doi：10.3390/ijms17081249.
[26] Yang Y，Zhang Y，Wang Z，et al. Attenuation of acute phase injury in rat intracranial hemorrhage by cerebrolysin that inhibits brain edema and inflammatory response [J]. Neurochem Res，2016，41（4）：748-757.
[27] 邱国平，孙善全，卓飞，等.脑出血脑组织中水通道蛋白4的极性表达缺失[J].重庆医科大学学报，2015，40（5）：666-670.
2019, Vol. 16 
京公网安备 11010502046598号