七十味珍珠丸对脑缺血再灌注损伤大鼠血脑屏障的保护作用
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摘要
目的考察七十味珍珠丸对脑缺血再灌注损伤大鼠血脑屏障的保护作用。方法线栓法建立大鼠脑缺血模型,2 h后再灌注。72只大鼠随机分为假手术组、模型对照组、尼莫地平片组(30.00 mg/kg)、七十味珍珠丸组(66.68 mg/kg),每组再分为3个亚组(脑梗死率、血脑屏障通透性、脑组织形态学),于脑缺血再灌注后2、24 h观察神经行为学变化,24 h检测脑梗死率、血清SOD活性和MDA水平、血脑屏障通透性、缺血侧脑组织病理变化和尼氏小体数。结果与模型对照组比较,七十味珍珠丸组显著降低大鼠脑梗死率(P<0.01)和缺血侧脑组织伊文思蓝(EB)含有量(P<0.05),显著改善神经行为学异常(P<0.01),显著增加尼氏小体数(P<0.05),脑组织病理变化、SOD活性、MDA水平有改善趋势,但无显著性差异(P>0.05)。结论七十味珍珠丸对脑缺血再灌注损伤大鼠脑组织有明显保护作用,其机制可能与抑制血脑屏障通透性增加有关。
AIM To investigate the protective effects of Qishiwei Zhenzhu Pills on blood-brain barrier in cerebral ischemia-reperfusion injury rats.METHODS Suture-occluded method was applied to establishing the rat model for cerebral ischemia, followed by reperfusion after 2 h. Seventy-two rats were randomly divided into sham-operation group, model control group, Nimodipine Tablets group(30.00 mg/kg) and Qishiwei Zhenzhu Pills group(66.68 mg/kg), each group was further divided into three subgroups(cerebral infarction rate, blood-brain barrier permeability and brain histomorphology). At 2, 24 h after cerebral ischemia-reperfusion, neurobehavioral changes were observed; at 24 h, cerebral infarction rate, SOD activity and MDA level in serum, blood-brain barrier permeability, pathological changes and Nissl body count in ischemic brain tissue were detected.RESULTS Compared with the model control group, the Qishiwei Zhenzhu Pills group demonstrated significantly decreased cerebral infarction rate(P<0.01) and Evans blue(EB) content in ischemic brain tissue(P<0.05), markedly improved neurobehavioral abnormalities(P<0.01), obviously increased Nissl body count(P<0.05), and improvement trends in brain tissue pathological changes, SOD activity, MDA level without significant differences(P>0.05).CONCLUSION Qishiwei Zhenzhu Pills exhibit obvious protective effects on brain tissue in cerebral ischemia-reperfusion injury rats, whose mechanism may contribute to the inhibition of increase of blood-brain barrier permeability.
AIM To investigate the protective effects of Qishiwei Zhenzhu Pills on blood-brain barrier in cerebral ischemia-reperfusion injury rats.METHODS Suture-occluded method was applied to establishing the rat model for cerebral ischemia, followed by reperfusion after 2 h. Seventy-two rats were randomly divided into sham-operation group, model control group, Nimodipine Tablets group(30.00 mg/kg) and Qishiwei Zhenzhu Pills group(66.68 mg/kg), each group was further divided into three subgroups(cerebral infarction rate, blood-brain barrier permeability and brain histomorphology). At 2, 24 h after cerebral ischemia-reperfusion, neurobehavioral changes were observed; at 24 h, cerebral infarction rate, SOD activity and MDA level in serum, blood-brain barrier permeability, pathological changes and Nissl body count in ischemic brain tissue were detected.RESULTS Compared with the model control group, the Qishiwei Zhenzhu Pills group demonstrated significantly decreased cerebral infarction rate(P<0.01) and Evans blue(EB) content in ischemic brain tissue(P<0.05), markedly improved neurobehavioral abnormalities(P<0.01), obviously increased Nissl body count(P<0.05), and improvement trends in brain tissue pathological changes, SOD activity, MDA level without significant differences(P>0.05).CONCLUSION Qishiwei Zhenzhu Pills exhibit obvious protective effects on brain tissue in cerebral ischemia-reperfusion injury rats, whose mechanism may contribute to the inhibition of increase of blood-brain barrier permeability.
引文
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[13] 梁未雯,黄春娟,王张,等.藏药七十味珍珠丸对线栓致大鼠局灶性脑缺血再灌注损伤的时效关系初步研究[J].中药药理与临床,2015,31(1):182-187.
[14] 王张,张艺,赵启鹏,等.灯盏细辛治疗脑缺血再灌注损伤的时-效关系初步研究[J].中药药理与临床,2012,28(2):62-64.
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[19] 高兰,娄季宇,杨霄鹏.丁苯酞对脑缺血再灌注损伤大鼠MMP-9活性和血脑屏障通透性的影响[J].中风与神经疾病杂志,2012,29(2):116-118.
[20] Zhang H T,Zhang P,Gao Y,et al.Early VEGF inhibition attenuates blood-brain barrier disruption in ischemic rat brains by regulating the expression of MMPs[J].Mol Med Rep,2017,15(1):57-64.
[21] Wang X,Kang K,Wang S Q,et al.Focal cerebral ischemic tolerance and change in blood-brain barrier permeability after repetitive pure oxygen exposure preconditioning in a rodent model[J].J Neurosurg,2016,125(4):943-952.
[22] Liang J,Qi Z F,Liu W L,et al.Normobaric hyperoxia slows blood-brain barrier damage and expands the therapeutic time window for tissue-type plasminogen activator treatment incerebral ischemia[J].Stroke,2015,46(5):1344-1351.
[23] Liu Y S,Liu W C,Sun Y Y,et al.Normobaric hyperoxia extends neuro- and vaso-protection of N-acetylcysteine in transient focal ischemia[J].Mol Neurobiol,2017,54(5):3418-3427.
[24] 史秀丽.局灶性脑缺血再灌注后血脑屏障通透性改变与MMP-2表达的时相研究[D].合肥:安徽医科大学,2005.
[25] 黄萍,夏厚林,贾芳,等.安息香配伍合成冰片对小鼠脑缺血缺氧及血脑屏障通透性的影响[J].中药药理与临床,2013,29(5):75-78.
[26] 张玉琴,李煌,许文,等.栝楼桂枝颗粒对脑缺血再灌注损伤大鼠的血脑屏障通透性及神经保护作用[J].中华中医药杂志,2015,30(5):1410-1417.
[27] 任丽,孙善全.尼膜同对大鼠脑缺血再灌注后血-脑屏障通透性和脑梗死体积的影响[J].临床神经病学杂志,2004,17(3):187-190.
[28] 左世伦.青蒿琥酯对大鼠蛛网膜下腔出血后血脑屏障的保护及机制研究[D].重庆:第三军医大学,2016.
[29] 徐文龙,梁源,王张,等.HPLC法同时测定七十味珍珠丸中6种成分[J].中成药,2017,39(10):2072-2076.
[30] 李莉,冯晶晶,李铁军,等.复元醒脑汤对大鼠局灶性脑缺血再灌注损伤的保护作用研究[J].药学实践杂志,2018,36(1):34-39.
[31] 侯伯南.黄芪甲苷对缺血再灌注损伤后血脑屏障的预保护作用机制研究[D].广州:广州中医药大学,2017.
[32] Abbott N J,Patabendige A A K,Dolman D E M,et al.Structure and function of the blood-brain barrier[J].Neurobiol Dis,2010,37(1):13-25.
[33] Esposito E,Cordaro M,Cuzzocrea S.Roles of fatty acid ethanolamides (FAE) in traumatic and ischemic brain injury[J].Pharmacol Res,2014,86:26-31.
[34] Bertoni S,Arcaro V,Vivo V,et al.Suppression of inflammatory events associated to intestinal ischemia-reperfusion by 5-HT1A blockade in mice[J].Pharmacol Res,2014,81:17-25.
[35] Zlokovic B V.The blood-brain barrier in health and chronic neurodegenerative disorders[J].Neuron,2008,57(2):178-201.
[36] 万嘉洋,万海同,何昱,等.活血康脑颗粒对大鼠脑缺血再灌注损伤的保护作用[J].中成药,2017,39(11):2236-2242.
[2] 潘琳娜,杨旸,樊萍,等.基于TRIF-IFNβ信号通路补阳还五汤抗气虚血瘀证脑缺血损伤作用[J].时珍国医国药,2016,27(9):2119-2121.
[3] 郭东艳,范妤,赵晓平,等.不同制备工艺的健脑益智胶囊对脑缺血再灌注损伤大鼠的保护作用[J].中成药,2015,37(11):2530-2534.
[4] 孔亮.缺血性脑中风神经炎症调控及血脑屏障损伤保护相关研究[D].济南:山东大学,2017.
[5] 刘明.乌司他丁对全脑缺血再灌注损伤大鼠血脑屏障通透性和Caveolin-1蛋白表达的影响[D].上海:复旦大学,2014.
[6] Sun L,Yang L,Xu Y W,et al. Neuroprotection of hydroxysafflor yellow A in the transient focal ischemia:inhibition of protein oxidation/nitration,12/15-lipoxygenase and blood-brain barrier disruption[J].Brain Res,2012,1473:227-235.
[7] Takeshita T,Nakagawa S,Tatsumi R,et al.Cilostazol attenuates ischemia-reperfusion-induced blood-brain barrier dysfunction enhanced by advanced glycation endproducts via transforming growth factor-β1 signaling[J].Mol Cell Neurosci,2014,60:1-9.
[8] Chen X D,Sadowska G B,Zhang J Y,et al.Neutralizing anti-interleukin-1β antibodies modulate fetal blood-brain barrier function after ischemia[J].Neurobiol Dis,2015,73:118-129.
[9] Liu Z,Liu Q,Cai H,et al.Calcitonin gene-related peptide prevents blood-brain barrier injury and brain edema induced by focal cerebral ischemia reperfusion[J].Regul Pept,2011,171(1-3):19-25.
[10] De Bock M,Wang N,Decrock E,et al.Endothelial calcium dynamics,connexin channels and blood-brain barrier function[J].Prog Neurobiol,2013,108:1-20.
[11] 国家药典委员会.中华人民共和国药典:2015年版一部[S].北京:中国医药科技出版社,2015:450-451.
[12] 徐文龙,孙位军,王张,等.七十味珍珠丸抗大鼠脑缺血再灌注损伤的量效关系研究[J].现代药物与临床,2017,32(1):10-15.
[13] 梁未雯,黄春娟,王张,等.藏药七十味珍珠丸对线栓致大鼠局灶性脑缺血再灌注损伤的时效关系初步研究[J].中药药理与临床,2015,31(1):182-187.
[14] 王张,张艺,赵启鹏,等.灯盏细辛治疗脑缺血再灌注损伤的时-效关系初步研究[J].中药药理与临床,2012,28(2):62-64.
[15] Longa E Z,Weinstein P R,Carlson S,et al.Reversible middle cerebral artery occlusion without craniectomy in rats[J].Stroke,1989,20(1):84-91.
[16] Bederson J B,Pitts L H,Tsuji M,et al.Rat middle cerebral artery occlusion:evaluation of the model and development of a neurologic examination[J].Stroke,1986,17(3):472-476.
[17] Zhou Y,Li H Q,Lu L,et al.Ginsenoside Rg1 provides neuroprotection against blood brain barrier disruption and neurological injury in a rat model of cerebral ischemia/reperfusion through downregulation of aquaporin 4 expression[J].Phytomedicine,2014,21(7):998-1003.
[18] 谢琛.大鼠脑缺血再灌注后炎性因子、神经细胞凋亡、血脑屏障变化的动态研究[D].南昌:南昌大学,2014.
[19] 高兰,娄季宇,杨霄鹏.丁苯酞对脑缺血再灌注损伤大鼠MMP-9活性和血脑屏障通透性的影响[J].中风与神经疾病杂志,2012,29(2):116-118.
[20] Zhang H T,Zhang P,Gao Y,et al.Early VEGF inhibition attenuates blood-brain barrier disruption in ischemic rat brains by regulating the expression of MMPs[J].Mol Med Rep,2017,15(1):57-64.
[21] Wang X,Kang K,Wang S Q,et al.Focal cerebral ischemic tolerance and change in blood-brain barrier permeability after repetitive pure oxygen exposure preconditioning in a rodent model[J].J Neurosurg,2016,125(4):943-952.
[22] Liang J,Qi Z F,Liu W L,et al.Normobaric hyperoxia slows blood-brain barrier damage and expands the therapeutic time window for tissue-type plasminogen activator treatment incerebral ischemia[J].Stroke,2015,46(5):1344-1351.
[23] Liu Y S,Liu W C,Sun Y Y,et al.Normobaric hyperoxia extends neuro- and vaso-protection of N-acetylcysteine in transient focal ischemia[J].Mol Neurobiol,2017,54(5):3418-3427.
[24] 史秀丽.局灶性脑缺血再灌注后血脑屏障通透性改变与MMP-2表达的时相研究[D].合肥:安徽医科大学,2005.
[25] 黄萍,夏厚林,贾芳,等.安息香配伍合成冰片对小鼠脑缺血缺氧及血脑屏障通透性的影响[J].中药药理与临床,2013,29(5):75-78.
[26] 张玉琴,李煌,许文,等.栝楼桂枝颗粒对脑缺血再灌注损伤大鼠的血脑屏障通透性及神经保护作用[J].中华中医药杂志,2015,30(5):1410-1417.
[27] 任丽,孙善全.尼膜同对大鼠脑缺血再灌注后血-脑屏障通透性和脑梗死体积的影响[J].临床神经病学杂志,2004,17(3):187-190.
[28] 左世伦.青蒿琥酯对大鼠蛛网膜下腔出血后血脑屏障的保护及机制研究[D].重庆:第三军医大学,2016.
[29] 徐文龙,梁源,王张,等.HPLC法同时测定七十味珍珠丸中6种成分[J].中成药,2017,39(10):2072-2076.
[30] 李莉,冯晶晶,李铁军,等.复元醒脑汤对大鼠局灶性脑缺血再灌注损伤的保护作用研究[J].药学实践杂志,2018,36(1):34-39.
[31] 侯伯南.黄芪甲苷对缺血再灌注损伤后血脑屏障的预保护作用机制研究[D].广州:广州中医药大学,2017.
[32] Abbott N J,Patabendige A A K,Dolman D E M,et al.Structure and function of the blood-brain barrier[J].Neurobiol Dis,2010,37(1):13-25.
[33] Esposito E,Cordaro M,Cuzzocrea S.Roles of fatty acid ethanolamides (FAE) in traumatic and ischemic brain injury[J].Pharmacol Res,2014,86:26-31.
[34] Bertoni S,Arcaro V,Vivo V,et al.Suppression of inflammatory events associated to intestinal ischemia-reperfusion by 5-HT1A blockade in mice[J].Pharmacol Res,2014,81:17-25.
[35] Zlokovic B V.The blood-brain barrier in health and chronic neurodegenerative disorders[J].Neuron,2008,57(2):178-201.
[36] 万嘉洋,万海同,何昱,等.活血康脑颗粒对大鼠脑缺血再灌注损伤的保护作用[J].中成药,2017,39(11):2236-2242.
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