Role of candesartan against cerebral ischemia and oxidative damage in normotensive rats

Objective Angiotensin Ⅱ (Ang Ⅱ ) contributes to modulating blood pressure by stimulation of Ang Ⅱ AT1 receptors. We devised a rat transient middle cerebral artery occlusion (MCAO) model to assess whether oxidative damage is decreased after pretreatment with Angiotensin Ⅱ AT1 receptor blocker (ARB). Methods After 2 weeks pretreatment with ARB 0. 5 and 1 mg/kg, the male Wister rats were subjected to 2 h middle cerebral artery occlusion (MCAO). At 24 h, the lumen diameter of middle cerebral artery, the plasma level of 8-hydroxy-2'-deoxyguanosine (8-OHdG), and HIF-1 a levels were recorded and compared. Results After pretrcatment with ARB 0.5 and 1 mg/kg, blood pressure did not significantly change compared with that of controls. In the group of candesartan at 1 mg/(kg· day), the lumen diameter was significantly increased compared to that in control group [(86.0±5.0) μm vs. (69.0± 2.1) μm; P<0. 01, n = 6- 8]. The plasma 8-OHdG levels of ARB pretreatment groups were decreased. In immunohistochemical findings, 8-OHdG- and HIF-1α-containing cells in ARB pretreatment groups were decreased. Conclusion Brain ischemia and oxidative damage can be reversed by AT1 receptor blockade in normotensive rats after transient cerebral artery occlusion.     

纳洛酮对大鼠局灶性脑缺血再灌注损伤的保护作用

目的　观察纳洛酮对大鼠局灶性脑缺血再灌注损伤的保护作用。方法　用改良Longa法制作局灶性脑缺血再灌注损伤模型 ,观察不同剂量纳洛酮对模型大鼠神经功能障碍、脑梗死范围、脑组织病理改变以及血清中乳酸脱氢酶(LDH)和肌酸激酶 (CK)含量的影响。结果　纳洛酮能剂量依赖性地降低模型大鼠的血清LDH、CK ,减少梗死面积 ,降低神经功能行为评分 ,减轻脑组织病理改变。结论　纳洛酮对大鼠局灶性脑缺血再灌注损伤有一定的保护作用     

自发性高血压大鼠大、中动脉壁AT1和AT2受体表达的增龄性变化

目的以自发性高血压大鼠(SHR)为研究对象,探讨动脉血管壁胶原成分、血管紧张素Ⅱ受体(ATR)AT1和AT2亚型蛋白表达的增龄性改变。方法幼年组(7周)、成年组(26周)、老年组(51周)雄性SHR各20只,正常饮食饲养1周后,测定鼠尾动脉收缩压;胸主动脉及肠系膜上动脉(SMA)取材后,石蜡切片,Mallory染色观察壁纤维化程度,免疫组化SABC法测定ATR蛋白表达。结果 3个年龄组SHR大鼠的血压随增龄呈现明显升高[(151±26)mmHg vs.(166±9.0)mmHg vs.(180±13)mmHg,P<0.05];胸主动脉和SMA壁Ⅰ型和Ⅲ型胶原纤维沉积亦随增龄增多(IA值:主动脉416±43 vs.483±74 vs.553±83,SMA 387±46 vs.425±67 vs.468±81,P均<0.05);胸主动脉和SMA壁AT1和AT2表达均随年龄增长呈增高趋势(灰度值:胸主动脉AT1 159±7.0 vs.150±8.7 vs.139±8.9,AT2 187±6.9 vs.181±9.5 vs.169±10;SMA AT1 163±11 vs.112±11 vs.128±18,AT2 188±11 vs.171±15 vs.171±13;P均<0.05),AT1/AT2比值仅在老龄组增高(幼龄及老龄组胸主动脉0.86±0.01 vs.0.78±0.08;SMA 0.85±0.07 vs.0.71±0.08,P均<0.05)。结论增龄可导致SHR成纤维细胞生长、胶原纤维沉积,血管壁局部AT1、AT2表达及二者比例改变,同时AT1由单纯的介导血管收缩作用转变为介导血管壁重塑,可能是SHR大鼠血压增龄性改变的机制之一。     

二维三七桂利嗪胶囊对急性脑缺血的保护作用

目的观察二维三七桂利嗪胶囊对于急性脑缺血的影响。方法ICR小鼠分别用420 mg/kg、210 mg/kg、105 mg/kg的二维三七桂利嗪胶囊灌胃10 d,观察断头后小鼠的喘息时间;SD大鼠分别用292 mg/kg、146 mg/kg、73 mg/kg的二维三七桂利嗪胶囊灌胃10 d,线栓法制备大鼠大脑中动脉栓塞模型,然后进行神经行为指标评分、脑梗死范围测定和病理学观察。结果二维三七桂利嗪胶囊各剂量组均能延长小鼠断头后的喘息时间,缩小局灶性脑缺血大鼠脑梗死范围,改善神经症状,减轻光镜下脑组织缺血性损伤。结论二维三七桂利嗪胶囊对急性脑缺血损伤具有保护作用。     

THE EFFECT OF LIGUSTRAZINE ON NEUROGENESIS IN CORTEX AFTER FOCAL CEREBRAL ISCHEMIA IN RATS

Objective To explore the effect of Ligustrazine on neurogenesis in cortex after focal cerebral ischemia in rats. Methods Focal cerebral ischemia was induced by left middle cerebral artery occlusion with a suture. Two hours later, injection of Ligustrazine （80 mg/kg, 1 time/d） was performed peritoneally. Four hours after the ischemia, 5-bromodeoxyuridine （BrdU） （50 mg/kg, 1 time/d） was injected peritoneally. At 7 d, 14 d and 21 d after ischemia, BrdU positive cells in the cortex were observed by cal staining. Results In ischemic model group, at 7 day, sparsely-distributed BrdU positive cells were observed in the Ⅱ-- Ⅵ layers of the ipsilateral cortex, with a bandlike distribution in ischemic penumbra. With the prolongation of ischemia, the number of BrdU positive cells increased. In Ligustrazine group, BrdU positive cells were also observed in theⅡ-- Ⅵ layers of the cortex, with an intense distribution in ischemic penumbra. The numbers of BrdU positive cells at 7 d, 14 d and 21 d were more than those in ischemic model group respectively. Conclusion Ligustrazine increases the proliferated cells in cortex after focal cerebral ischemia in rats. The results suggest that it may be useful for promoting self-repair after ischemia.     

川芎嗪对大鼠局灶性脑缺血损伤的神经保护作用

目的观察川芎嗪对局灶性脑缺血后脑损伤的保护作用。方法采用线栓法制作大鼠左侧大脑中动脉阻塞模型。氯化三苯基四氮唑(TTC)脑片染色测定脑梗死体积,干湿重法测定脑组织含水量,快速Golgi银染方法观察脑缺血周围区神经元的形态改变。结果川芎嗪能明显缩小脑梗死体积、降低脑组织含水量,随着川芎嗪剂量增大,作用更为明显,具有剂量依赖性。脑缺血后14 d Golgi银染显示,模型组在梗死周围区神经元明显减少,变性和正常神经元共存。变性神经元主要表现为突起断裂、增粗,突起有大的串珠,树突棘减少。川芎嗪组较模型组皮质梗死周围神经元变性较少。结论川芎嗪能缩小脑梗死体积、减轻脑水肿、保护缺血周围神经元,证实川芎嗪对脑缺血损伤有保护作用。     

急诊手术治疗颈内动脉血栓形成闭塞性脑卒中

目的探讨应用急诊手术方法治疗颈内动脉血栓形成闭塞性脑卒中的可行性方法。方法对2例急性颈内动脉血栓形成闭塞性脑卒中患者,采用全身麻醉下急性颈内动脉切开、血栓取出、颈动脉内膜切除及血管成形术。结果2例患者脑缺血症状均得到明显改善,1例完全康复,1例生活自理。随访1-9个月未见血栓形成及血管再狭窄。结论急诊手术治疗颈内动脉血栓形成闭塞性脑卒中的方法是安全可行的。     

黄芪预处理对大鼠心肌缺血再灌注损伤的保护作用及其机制

目的 探讨黄芪对大鼠缺血再灌注心肌的保护作用及其机制.方法 采用结扎左冠状动脉的方法制备心肌缺血再灌注损伤动物模型.SD大鼠30只随机分为3组:对照组、缺血再灌注组(I/R)和黄芪预处理组(H+I/R).光镜和透射电镜下观察心肌病理变化,检测血清肌酸激酶(CK)、乳酸脱氢酶(LDH)、超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量,以及心肌组织Na~+K~+-ATP酶(Na~+K~+-ATPase)、Ca~(2+)-ATP酶(Ca~(2+)-ATPase)活性.结果 ①黄芪预处理组光镜和透射电镜下心肌细胞变性坏死程度及心肌细胞超微结构形态改变较缺血再灌注组显著减轻;②黄芪预处理组大鼠血清中CK、LDH活性和MDA含量显著降低(P<0.05),SOD、Na+ K+-ATPase、Ca~(2+)-ATPase活性显著提高(P<0.05).结论 黄芪对大鼠冠状动脉结扎后再灌注心肌损伤具有明显的保护作用,其机制可能与改善心肌缺血再灌注冠状微循环与抗氧自由基生成、减轻钙超载等多种机制有关.     

不同设计的两代国产铂铱合金支架对兔颈动脉血管反应的影响

目的　评估不同金属丝直径、不同结构设计的国产铂 铱合金支架对血管反应的影响。方法　将家兔分为三组 ,第一组置入直径 0 .1 3mm单丝缠绕成螺旋形结构的第一代支架 (n =5) ,第二组置入直径 0 .1 75mm单丝缠绕成“之”字形结构的第二代支架 (n =5) ,第三组置入第二代明胶蛋白涂层支架 (n =7)。术后 7d行病理形态分析及扫描电镜观察。结果　所有动物均成功置入支架 ,组织病理学检查显示 :一代和二代支架组各有 1例不完全性血栓形成 ;涂层支架组无血栓形成。支架置入血管无明显炎症反应和异物巨细胞聚集。涂层支架组平均新生内膜厚度与新生内膜面积最小 ,而管腔面积最大 (P均 <0 .0 5)。扫描电镜显示支架表面几乎完全内皮化。结论　支架金属丝直径与结构设计的不同对新生内膜增殖及管腔面积有影响 ;明胶蛋白涂层具有良好的组织相容性。     

c-Jun氨基末端激酶信号通路在大鼠脑缺血再灌注过程中的作用

目的探讨c-Jun氨基末端激酶(JNK)信号通路在大鼠脑缺血再灌注过程中所发挥的作用。方法雄性SD大鼠108只,体重290-310 g,随机分成假手术组(SH组)、缺血再灌注组(IR组)和JNK抑制剂SP600125组(SP组),分别于缺血前30 min侧脑室注射10 mL/L二甲基亚砜(DMSO)1、0 mL/L DMSO及JNK抑制剂SP600125。每组再根据再灌注时间分为2、6、12、24、487、2 h 6个亚组,每亚组6只动物。采用4-VO法建立SD大鼠全脑缺血模型,在预定时间点行灌注、固定、取脑、石蜡包埋切片;免疫组化方法检测p-JNK的表达变化,光镜下计数海马CA1区存活细胞,TUNEL法检测CA1区凋亡细胞。结果脑缺血再灌注后海马CA1区p-JNK在IR组有明显表达,于再灌注2 h时即明显升高,6 h时略有降低,后逐渐上升,24 h到高峰,之后表达量减小。SP组p-JNK的表达则无明显增高,各时点与IR组比较均有显著性差异(P<0.01)。海马CA1区神经元存活数目SP组明显高于IR组(P<0.01),凋亡指数显著低于IR组(P<0.01)。结论在大鼠全脑缺血再灌注损伤过程中,JNK信号通路发挥了重要作用,抑制JNK通路的激活可对脑缺血再灌注损伤导致的细胞损伤起到保护作用。     

急救止血敷片的止血作用

目的 观察急救止血敷片的止血作用.方法 用试管法观察体外凝血时间,用大鼠和犬股动脉出血模型、兔肝溢血模型研究止血作用.结果 试管法体外凝血试验结果显示,急救止血敷片大、中、小3个浓度的凝血时间(4.9±1.3)min、(5.7±1.8)min和(5.8±1.3)min均明显短于对照组[(14.4±1.6)min].大鼠、犬股动脉出血模型试验结果显示,急救止血敷片3个剂量组能显著减少大鼠股动脉破裂的出血量和出血时间,与PVF海绵贴片组比较有明显差异(P<0.01或P<0.05).兔肝溢血模型试验结果显示,急救止血敷片3个剂量组能显著缩短家兔肝破裂的出血时间,减少出血量,与无菌纱布组出血时间比较均有显著差异(P<0.01).结论 急救止血敷片能明显缩短凝血时间、出血时间,减少出血量.     

益气活血开窍复方对缺血再灌注脑组织兴奋性氨基酸及超微结构的影响

目的　探讨益气活血开窍复方对缺血再灌注脑组织保护作用的机理。方法　以线栓法制备大鼠脑缺血再灌注模型 ,采用全自动氨基酸分析仪、干湿重法、原子吸收分光光度计测量脑组织中兴奋性氨基酸 (EAA)含量、含水量及钙离子 (Ca2 + )含量 ,电子显微镜观察脑组织超微结构改变。结果　中药组谷氨酸 (Glu)含量下降 (P <0 .0 1) ,谷氨酸 /γ 氨基丁酸 (Glu/GABA)趋向于正常比值 ,脑组织含水量及Ca2 + 浓度下降 (P <0 .0 5 )。中药可减轻由于缺血再灌注所导致的细胞超微结构的改变。结论　益气活血开窍方通过抑制EAA释放、Ca2 + 内流而发挥脑组织保护作用。     

高压氧对缺氧缺血性脑损伤大鼠感觉运动功能及大脑皮质区神经元的远期影响

目的探讨高压氧(HBO)对缺氧缺血性脑损伤(HIBD)新生大鼠远期的感觉运动功能和脑皮质区神经元的保护作用。方法24只7d龄SD大鼠随机分为3组(n=8):假手术组(sham)、HIBD组、HIBD+HBO组。HIBD+HBO组大鼠在HIBD后1h应用0.25MPa的高压氧单次干预1.5h。在大鼠5周龄时应用握力实验和转杆实验评价其感觉运动功能。在大鼠9周龄时灌注取脑,观察脑皮质区神经元死亡和丢失情况。结果在5d的抓握实验中,sham组和HIBD+HBO组的平均抓握时间明显长于HIBD组;HIBD+HBO组与HIBD组比较,在第2、3、4、5天其抓握时间明显延长。在5d的转杆试验测试中,sham组和HIBD+HBO组转杆的平均停留时间明显长于HIBD组;在第5天,sham组和HIBD+HBO组的动物在转杆上停留的时间比HIBD组明显延长。HIBD+HBO组大鼠的脑组织大体病理变化比HIBD组轻,且损伤侧的皮质区神经元没有明显的死亡和丢失。结论新生大鼠HIBD后1h给予单次高压氧(0.25MPa,1.5h)治疗,可以有效地改善大鼠远期的感觉运动功能,同时也可以减轻大鼠大脑皮质区神经元的死亡与丢失。     

ALTERATION IN CONTRACTILE RESPONSE TO NORADRENALINE,5-HYDROXYTRYPTAMINE,SARAFOTOXIN 6c,AND ANGIOTENSINⅡIN RAT MESENTERIC ARTERY DURING ORGAN CULTURE

Objective To compare the vasoconstrictive effects of 9 mediators on fresh and incubated mesenteric arteries of rats. Methods The superior mesenteric artery of rat was removed and the endothelium was denuded. The vessels were cut into 1 mm long cylindrical segments and subjected to organ culture for 24 hours. Fresh or incubated segments were immersed into tissue baths and the concentration-response curves were obtained by cumulative administration of the vasoconstrictors. Results In fresh mesenteric artery, endothelin-1 (ET-1), 5-hydroxytryptamine (5-HT), noradrenaline (NA), 5-carboxamidotryptamine (5-CT), and angiotensinⅡ (AngⅡ) induced potent and sustained constrictions in a concentration-dependent manner. The contraction induced by sarafotoxin 6c (S6c) was weak, while bradykinin (BK), des-Arg-bradykinin (DA-BK), and human urotensinⅡ (hUT-II) showed no detectable contraction. The concentraion-response curves in order of slopes was ET-1, NA, 5-HT, 5-CT, and AngⅡ. The order of the maximum contractions was ET-1>NA=5-HT=5-CT>AngⅡ>S6c. After organ culture, the concentration-response curves induced by S6c, NA, and 5-HT were significantly increased, while that induced by AngⅡ was decreased as comparing to fresh arteries. BK contracted the artery only weakly. Conclusion Organ culture changed the phenotypes towards an increased efficacy of NA, 5-HT, S6c, and a reduced efficacy of AngⅡ, which is in accordance with the results of pharmacological characterization in some human vascular disease.     

川芎嗪对成体大鼠脑缺血再灌注损伤后海马齿状回细胞增殖的影响

目的研究川芎嗪(tetramethylpyrazine,TMP)对大鼠脑缺血再灌注损伤后海马齿状回(dentate gyrus,DG)细胞增殖的影响。方法成年雄性SD大鼠行2 h大脑中动脉阻塞手术,术后2 h开始腹腔注射TMP[40 mg/(kg.d)]。手术后腹腔注射5-溴脱氧尿核苷(5-bromodeoxyuridine,BrdU),末次注射24 h后处死动物,免疫组化染色观察TMP对脑缺血再灌注损伤后DG细胞增殖的作用。结果正常组和假手术组在DG有少量BrdU阳性细胞,对照组缺血后1 d阳性细胞开始增加,14 d达到高峰(P<0.05),TMP治疗组缺血后1 d损伤侧BrdU阳性细胞数开始增加,7 d达高峰(P<0.05)。结论TMP能促进缺血再灌注损伤大鼠海马齿状回内源性神经干细胞增殖。     

β-IRRADIATION WITH A LIQUID~(188)Re-FILLED BALLOON PREVENTS NEOINTIMAL PROLIFERATION IN THE CAROTID OF RABBIT

Ｐｅｒｃｕｔａｎｅｏｕｓｔｒａｎｓｌｕｍｉｎａｌｃｏｒｏｎａｒｙａｎｇｉｏｐｌａｓｔｙ(ＰＴＣＡ )ｉｓｏｎｅｏｆｔｈｅｍｏｓｔｃｕｒｒｅｎｔｔｈｅｒａｐｉｅｓｆｏｒｃｏｒｏｎａｒｙａｒｔｅｒｙｄｉｓｅａｓｅ ,ｂｕｔｉｔｒｅｍａｉｎｓｌｉｍｉｔｅｄｂｙａ30 %ｔｏ 6 0 %ｒｅｓｔｅｎｏｓｉｓｒａｔｅ .Ｉｎｔｒａｖａｓｃｕｌａｒｂｒａｃｈｙｔｈｅｒａｐｙ (ＩＶＢ)ｉｓａｎｅｆｆｅｃｔｉｖｅｍｅｔｈｏｄｔｏｉｎｈｉｂｉｔｃｏｒｏｎａｒｙｒｅｓｔｅｎｏｓｉｓａｆｔｅｒＰＴＣＡ .Ａｎｅｗｃｏｎｃｅｐｔｏｆｐｒｅ…     

EFFECT OF STENT ABSORBED c-myc ANTISENSE OLIGODEOXYNUCLEOTIDE ON SMOOTH MUSCLE CELLS APOPTOSIS IN RABBIT CAROTID ARTERY

Ｉｎｔｈｅｐａｓｔｆｅｗ ｙｅａｒｓ ,ｗｅｈａｖｅｗｉｔｎｅｓｓｅｄａｄｒａ ｍａｔｉｃ ｐｒｏｌｉｆｅｒａｔｉｏｎｉｎｔｈｅｕｓｅｏｆｉｎｔｒａｃｏｒｏｎａｒｙｓｔｅｎｔｓ.Ｓｔｅｎｔｓｎｏｗａｃｃｏｕｎｔｆｏｒｏｖｅｒ 70 %ｏｆｐｅｒｃｕｔａ ｎｅｏｕｓｔｒａｎｓｌｕｍｉｎａｌｃｏｒｏｎａｒｙａｎｇｉｏｐｌａｓｔｙ (ＰＴＣＡ ) .Ｈｏｗｅｖｅｒ,ｉｎ ｓｔｅｎｔｒｅｓｔｅｎｏｓｉｓｒｅｍａｉｎｓａｍａｊｏｒｐｒｏｂ ｌｅｍ ,ｏｃｃｕｒｉｎｇｉｎ 2 0 %～ 30 %ｏｆｔｈｅｓｅ ｐｒｏｃ ｅｄｕｒｅｓ[1-3] .Ｉ…     

EFFECT OF ANGIOTENSIN Ⅱ RECEPTOR SUBTYPE ⅠON THE FIRING RATE IN CATECHOLAMINERGIC TUMOR CELLS

AngiotensinⅡ (AngⅡ ) playsanimportantroleintheregulationofbloodpressure[1 ] .Theac tionofAngⅡismediatedmainlybystimulationoftheangiotensintype 1(AT1 )receptorandinvolvesintheactivityofcatecholaminergicsystem .Im munostainingstudieshaveindicatedthattheAT1 re ceptorexistsonthecatecholaminergicneurons[2 ] .AdministrationofAngⅡintorat’sbrainincreasedtheconcentrationsofdopamine ,epinephrine ,andnorepinephrineinthebrain[3 ] .Althoughanatomicalandfunctionalevidencessupporttheinteractionbe twe…     

PROLIFERATION AND MIGRATION OF EPENDYMAL CELLS IN THE BRAIN OF ADULT RATS AFTER PERMANENT FOCAL CEREBRAL ISCHEMIA

Objective Ependymal cells are thought to be the primary source of neural stem cells in the adult central nervous system. The purpose of this study is to examine spatial and temporal profiles of ependymal cell proliferation and migration after focal cerebral ischemia. Methods Eighty male Sprague Dawley rats underwent permanent middle cerebral artery occlusion after injection of 10/μL of 0.2% Dil into the lateral ventricle. Rats were sacrificed and brain sections were acquired for pathological evaluation and laser confocal imaging at day 1,3,7,11,14,21 and 28 after ischemia. Results The density of Dil-labeled cells in the ischemic ipsilateral subventricular zone was significantly higher than that in the control group and these labeled cells dispersed in the ischemic ipsilateral subventricular zone and/or were located in ependyma from day 1 to 11. In the ischemic ipsilateral cortex, some Diilabeled cells occurred in peri-infarction and infarction of parietal region at day14 and peaked at day 21 when some Dil-labeled cell nodules were found in this region. During postischemic day 14--28, a significant decrease in labeled celldensity in the ischemic ipsilateral subventricular zone was coincident with a significant increase in labeled cells density in the cortex (peri-infarction and infarction). Conclusion The results indicate that ependymal cells proliferate and migrate after focal cerebral ischemia in the adult rat brain.     

大鼠脑缺血淋巴细胞浸润的免疫组化研究

目的 探讨脑缺血后淋巴细胞浸润情况。方法 用免疫组化方法检测了30只大鼠大脑中动脉局部脑缺血12h、24h、3d、7d和10d后损伤区CD3、CD4和CD8阳性淋巴细胞。结果 缺血12～24h即可见CD3阳性和CD8阳性细胞浸润，3d和7d组阳性细胞最多。这些浸润的淋巴细胞位于反应带以及坏死中心和反应带的交界处。位于坏死区周围的CD3阳性和CD8阳性细胞主要为圆形，有大细胞和小细胞两种形态；位于反应带的淋巴细胞为小圆细胞，呈弥散分布，也可在微血管周围形成血管套。CD4阳性淋巴细胞数量较少，形态多样，大小不一。结论 淋巴细胞及亚群可能参与缺血性脑损伤的病理过程。