Kallikrein基因转导对脑缺血再灌注后局部血流灌注恢复的作用

目的 探讨Kallikrein基因对脑缺血再灌注后梗死灶周围血管增生与局部脑血流灌注恢复的作用.方法 建立大鼠脑缺血再灌注模型,术后将90只大鼠按照随机数字表法分为3组.每组30只,分别是空白对照组、注射生理盐水、注射pAdCMV-人组织激肽释放酶(HTK)组.各组大鼠又分为治疗后12 h、24 h及72 h组,每组各10只.治疗前后行大鼠神经功能缺损评分.TTC染色方法测定脑梗死面积的变化,用免疫组化检测外源性HTK的表达以及局部血管内皮生长因子(VEGF)的表达,并通过14C-iodoantipyrine微示踪技术检测局部脑血流灌注(rCBF)情况.结果 与其他两组相比,pAdCMV-HTK组大鼠脑梗死面积在治疗后24h已有明显减小,72h后这种变化更明显,差异有统计学意义(P<0.05);在治疗后24 h,pAdCMV-HTK组大鼠神经功能缺损评分明显低于生理盐水组及空白对照组,治疗后72h差异更明显,差异有统计学意义(P<0.05).vEGF阳性细胞主要分布于脑梗死灶周边皮质与部分白质;pAdCMV-HTK组VEGF表达在治疗后12h、24h、72h均明显高于生理盐水组及空白对照组,差异有统计学意义(P<0.05).各组缺血再灌注后脑梗死灶周围白质与皮质rCBF均较对侧稍减少:pAdCMV-HTK组治疗后12h,梗死灶周围白质与皮质rCBF较空白对照组与生理盐水组有增高.但不明显,差异无统计学意义(P>0.05),而在治疗24h、72 h后rCBF则明显增高,差异有统计学意义(P<0.05).结论 在脑缺血再灌注后,Kallikrein基因转导可增加梗死灶周围脑组织的血管增生,改善rCBF,减小梗死面积,从而达到保护缺血神经细胞功能的作用.     

腺病毒介导kallikrein基因过度表达对脑梗死周边区细胞凋亡的作用

目的 探讨激肽释放酶(kallikrein)对脑梗死周边区域缺血神经细胞凋亡的作用.方法 建立大鼠大脑中动脉闭塞(MCAO)模型,将造模成功的30只大鼠采用随机数字表法分为以下几组:A组,空白对照组;B组,注射生理盐水;C组,注射pAdCMV-人类组织激肽释放酶(HTK):每组10只.观察每组大鼠处理前后神经功能损害评分(NSS),用免疫组化技术检测外源性HTK的表达,并通过TUNEL染色、RT-PCR检测细胞凋亡及凋亡因子bcl-2、bax、caspase-3 mRNA水平.结果 治疗后24h在C组中可见HTK表达阳性细胞并逐渐增多,72h后达高峰.与B组以及A组相比差异有统计学意义(112±6.1、68±4.2、59±3.9,P<0.05).治疗后72h,C组大鼠NSS神经功能评分明显低于B组以及A组(6.70±0.16、8.13±0.16、7.93±0.20,P<0.05);治疗后7 d差异更明显(5.14±0.18、7.82±0.14、7.91±0.10,P<0.01).凋亡神经细胞集中于梗死周边区,治疗后72h及7d时,C组平均TUNEL阳性细胞数较B组与A组明显减少(72 h:10.1±0.9、16.7±1.1、20.4±0.8;7 d:15.2±1.2、33.6±1.3、28.8±1.7,P<0.05).与B、A组比较,C组中bc1.2 mRNA水平增高不明显(P>0.05);治疗后72 h及7 d,bax与caspase.3 mRNA水平则明显降低(P<0.05). 结论 Kallikrein可能通过减少凋亡因子bax、caspase-3的表达,抑制脑梗死周边区域的神经细胞凋亡,从而达到保护缺血神经细胞,改善神经功能的作用.     

润坦注射液对大鼠局灶性脑缺血再灌注后神经元凋亡的影响

目的研究润坦对局灶性脑缺血再灌注的神经保护效应.方法制备线栓法大脑中动脉闭塞再灌注模型,干预组每天给予润坦3 mg/kg,对照组给予等量生理盐水,每日对大鼠神经功能缺损进行评分,于再灌注12 h、24 h、48 h和5 d处死动物,切片作TUNEL原位凋亡检测.结果润坦可以显著改善术后第2 d大鼠的神经功能缺损(P＜0.05),降低致死率,减少再灌注24 h以后的细胞凋亡数目(P＜0.05).结论润坦可以抑制大鼠脑缺血再灌注后神经元凋亡,对急性期脑梗死可能有神经保护效应.     

人尿激肽原酶对局灶性脑缺血再灌注大鼠VEGF表达影响的研究

目的 探讨人尿激肽原酶对局灶性脑缺血再灌注大鼠脑组织血管内皮生长因子(VEGF)表达的影响.方法 采用随机数字表法将56只雄性SD大鼠分为假手术组(8只)、生理盐水组(24只)、人尿激肽原酶组(24只),其中生理盐水组、人尿激肽原酶组依据再灌注后不同取材时间又分为6 h,12 h,24 h,72 h,7 d五个亚组.采用线拴法制备大鼠局灶性脑缺血再灌注模型,采用神经功能评分、TTC染色、脑梗死体积测定、光镜检测等方法对不同组大鼠予以评价.采用免疫组化技术观察缺血再灌注不同时间点大鼠脑组织梗死中心区及半影区VEGF表达变化情况.结果 人尿激肽原酶组大鼠神经功能评分低于生理盐水组大鼠(P<0.05);24 h脑梗死体积测定,人尿激肽原酶组平均值为(53 261.96±7 326.75)μm3,生理盐水组平均值为(92 715.84±13 755.44)μm3,差异有统计学意义(P<0.05);人尿激肽原酶组VEGF表达在不同时间点均明显强于生理盐水组(P<0.05).结论 人尿激肽原酶能减轻脑缺血再灌注模型大鼠的神经功能损伤程度,减少脑梗死体积,促进VEGF的表达,具有脑缺血后神经保护作用.     

国产降纤酶对大鼠缺血/再灌注脑损伤的保护作用

目的观察3种国产降纤酶对大鼠缺血/再灌注脑损伤的保护作用。方法采用线栓法大鼠局灶性脑缺血/再灌注模型,观察3种国产降纤酶对缺血/再灌注不同时程动物脑梗死体积、血流量、神经功能缺损评分及梗死灶内肉眼出血率的影响。结果持续缺血3h,降纤酶治疗的各组动物脑梗死体积明显小于生理盐水对照组(P<0.05);缺血3h再灌注3h和72h,降纤酶治疗的各组动物脑梗死体积与生理盐水组相比无明显变化,但缺血3h再灌注6h和24h,降纤酶治疗的各组动物脑梗死体积比生理盐水组明显减少(P<0.05)。缺血3h再灌注6h、24h和72h,降纤酶治疗组动物脑血流量比生理盐水组明显增加(P<0.05)。但治疗组动物行为学评分较生理盐水组无相应改善,梗死灶内有肉眼出血的动物较生理盐水组多,但无统计意义。结论国产降纤酶能明显减小缺血/再灌注脑损伤动物的梗死体积和增加脑血流量,改善损伤后的低灌注状态,对脑组织有一定保护作用。     

Kallikrein Gene Transfer Induces Angiogenesis and Further Improves Regional Cerebral Blood Flow in the Early Period After Cerebral Ischemia/Reperfusion in Rats

SUMMARY Aims: The aims of this study were to find out whether kallikrein could induce angiogenesis and affect the cerebral blood flow (rCBF) in the early period after cerebral ischemia/reperfusion (CI/R). Methods: The adenovirus carried human tissue kallikrein (HTK) gene was administrated into the periinfarction region after CI/R. At 12, 24, and 72 h after treatments, neurological deficits were evaluated; expression of HTK and vascular endothelial growth factor (VEGF) were detected by immunohistochemistry staining; the infarction volume was measured; and rCBF was examined by ¹⁴C‐iodoantipyrine microtracing technique. Results: The expression of VEGF was enhanced significantly in pAdCMV‐HTK group than controls over all time points (P < 0.05). Furthermore, the rCBF in pAdCMV‐HTK group increased markedly than controls at 24 and 72 h after treatment (P < 0.05), and the improved neurological deficit was accompanied by reduced infarction volume in pAdCMV‐HTK group 24 and 72 h posttreatment. Conclusion: In the early period after CI/R, kallikrein could induce the angiogenesis and improve rCBF in periinfarction region, and further reduce the infarction volume and improve the neurological deficits.     

Neuroprotective effects of pretreatment with macrolide antibiotics on cerebral ischemia reperfusion injury

Abstract

Objective:

This study aims to determine if macrolide antibiotics have neuroprotective effects against transient cerebral ischemia.

Methods:

Sprague-Dawley rats were subjected to cerebral ischemia for 90 minutes followed by 24 or 72 hours of reperfusion. An oral suspension of roxithromycin (RXM), clarithromycin (CAM), erythromycin (EM), azithromycin (AZM), or kitasamycin (INN) was given at 10 or 100 mg/kg for 7 days before ischemia. The infarct volume, edema volume, and neurological performance were evaluated after 24 and 72 hours of reperfusion. The cerebral blood flow (CBF) was measured with a magnetic resonance imaging (MRI) system after 90 minutes of ischemia. Another experiment was conducted to investigate how the ischemic injury was affected by the interval from the antibiotic pretreatment to the ischemia in rats pretreated with CAM.

Results:

Roxithromycin, CAM, AZM, and INN significantly reduced the infarct volume in the high-dose group after 24 and 72 hours of reperfusion. All of the agents significantly decreased the edema in the high-dose groups at 24 and 72 hours, while only CAM and AZM significantly reduced the edema volume in the low-dose groups at 24 hours. All of the macrolide antibiotics at the high dose significantly improved neurological deficit scores at 24 and 72 hours. There were no differences in the CBF between the vehicle and respective antibiotic groups. In the experiment examining the interval, the 24-hour interval group exhibited the strongest neuroprotective effect.

Discussion:

These results demonstrate that the macrolide antibiotics RXM, CAM, EM, AZM, and INN may confer neuroprotective effects against ischemic damage following cerebral ischemia without affecting the CBF.     

"参芪脑保"治疗大鼠局灶脑缺血及再灌注损伤实验研究

目的　研究中药“参芪脑保”对脑缺血 再灌注损伤的治疗作用。方法　用线栓法制作大鼠大脑中动脉缺血 6小时再灌注模型 ,将大鼠随机分为对照组 (2 0只 )和参芪脑保治疗组 (2 0只 )。治疗组于术后 3小时始连续 7天给予参芪脑保灌胃治疗 ,观察神经功能缺损评分变化。各组大鼠于用药 7天后处死 ,行TTC和HE染色 ,测定脑梗死体积及神经元损伤情况。结果　参芪脑保治疗组大鼠 4 8小时死亡数 5只 (占2 5 % )低于对照组 10只 (占 5 0 % ) ,而 7天存活数 15只 (占 75 % )高于对照组 10只 (占 5 0 % )。参芪脑保治疗组梗死灶体积 (2 6 .5± 5 .2 )mm3 明显小于对照组 (4 1.9± 7.3)mm3 (P <0 .0 0 1) ,神经元缺失、脑梗死灶内出血较对照组减小。结论　“参芪脑保”对脑缺血 再灌注损伤有保护作用。     

Brain edema and tumor necrosis factor-like weak inducer of apoptosis in rats with cerebral ischemia

BACKGROUND： Recent studies have demonstrated that tumor necrosis factor-like weak inducer of apoptosis （TWEAK） participates in brain edema. However, it is unclear whether blood-brain barrier （BBB） disruption is associated with TWEAK during the process of brain edema OBJECTIVE： To investigate the effects of TWEAK on BBB permeability in brain edema. DESIGN, TIME AND SETTING： An immunohistochemical observation, randomized, controlled animal experiment was performed at the Laboratory of Neurosurgical Anatomy, Xiangya Medical College, Central South University ＆ Central Laboratory, Third Xiangya Hospital, Central South University between January 2006 and December 2007. MATERIALS： A total of 48 adult Wistar rats were randomly divided into three groups： normal control （n = 8）, sham-operated （n = 8）, and ischemia/reperfusion （n = 32）. Rats from the ischemia/reperfusion group were randomly assigned to four subgroups according to different time points, i.e., 2 hours of ischemia followed by 6 hours （n = 8）, 12 hours （n = 8）, 1 day （n = 8）, or 12 days （n = 8） of reperfusion. METHODS： Focal cerebral ischemia/reperfusion injury was induced by middle cerebral artery occlusion （MCAO） using the suture method in rats from the ischemia/reperfusion group. Thread was introduced at a depth of 17-19 mm. Rats in the sham-operated group were subjected to experimental procedures similar to the ischemia/reperfusion group; however, the introducing depth of thread was 10 mm. The normal control group was not given any intervention. MAIN OUTCOME MEASURES： TWEAK expression was examined by immunohistochemistry; brain water content on the ischemic side was calculated as the ratio of dry to wet tissue weight; BBB permeability was measured by Evans blue extravasation. RESULTS： A total of eight rats died prior to and after surgery and an additional eight rats were randomly entered into the study. Thus 48 rats were included in the final analysis. In the ischemia/reperfusion group, TWEAK-positiv     

阿托伐他汀对大鼠脑缺血再灌注后梗死灶周围中性粒细胞浸润和核转录因子-κB表达水平的影响

目的 观察阿托伐他汀对大鼠脑缺血再灌注后梗死灶周围中性粒细胞浸润以及核转录因子-κB表达水平的影响.方法 采用常规尼龙线栓法制备SD大鼠脑缺血再灌注模型,并将大鼠随机分为假手术组、大脑中动脉阻断再灌注(Middle cerebral artery occlusion/reperfusion,MCAO/R)(对照)组和M...     

星状神经节阻滞对全脑缺血再灌注家兔循环和呼吸的影响

目的　观察星状神经节阻滞 (SGB)对全脑缺血再灌注损伤家兔循环和呼吸的影响。方法　健康日本大耳白兔 15只 ,随机分成 3组 (A、B、C) ,每组 5只。三组动物均使用六血管 (双侧颈内外、椎动脉 )阻断法复制全脑缺血再灌注损伤模型 ,A、B两组分别接受左右侧SGB ,C组作为对照 ,不作SGB。连续观察全脑缺血 2 0min及再灌注 30min期间SGB对家兔心率 (HR)、平均动脉压 (MAP)以及呼吸频率 (RR)的影响。结果　在缺血及再灌注期间的部分时点A组HR、MAP变化较C组有显著意义 (P <0 .0 5 ) ;缺血后 1minB组MAP较C组显著降低 (P <0 .0 5 ) ;与B组比较 ,缺血后与再灌注期间的部分时段A组HR较快 ,MAP较低 (P <0 .0 5 ) ;各组内与缺血前比较 ,缺血后及再灌注开始的部分时段HR明显减慢 (P <0 .0 5 ) ,B、C两组尤为显著 ;MAP显著升高 (P <0 .0 5 ) ,A、C两组更为显著 ,部分时点P <0 .0 1,且C组在缺血一开始即出现显著性差异 (P <0 .0 5 )。组间未见RR的显著性变化。结论　SGB影响全脑缺血再灌注期间的心率和血压 ,倾向于减小其波动幅度 ,左侧对血压的影响以及右侧对心率的影响较对侧明显 ;SGB不改变缺血再灌注损伤对呼吸的影响     

Failure of levemopamil to improve histological outcome following temporary occlusion of the middle cerebral artery in cats

Levemopamil, a novel calcium channel blocker with antagonistic action on serotonin S₂-receptors has been reported to be a promising compound for therapy in cerebral ischemia. This data has been obtained in the rat only, and it is of interest to determine if these beneficial effects are present in other models of ischemia in other species. The present study was therefore designed to examine its effect on histological outcome and changes in EEG after focal cerebral ischemia and reperfusion in the cat. Focal cerebral ischemia was induced by a reversible 1 hour occlusion of the middle cerebral artery followed by reperfusion of the brain. Six hours after the induction of the insult, the brain was perfusion-fixed and evaluated for histological damage by light microscopy. In 8 animals an intravenous infusion of levemopamil was initiated 5 minutes after middle cerebral artery occlusion at a rate of 4 mg/kg/h for 15 min and then at 0.6 mg/kg/h until the end of the study. A control group (n = 7) received a similar infusion of saline. The EEG amplitude did not differ between the two groups at any point of the study. The area of ischemic damage in the sections obtained for histological examination at 1-mm intervals, as well as the total volume of ischemic damage for both groups (treated: 1.33 cm³; untreated: 0.97 cm³) also did not show any significant differences. These results indicate that postischemic treatment with levemopamil at this dose, and in this model of focal cerebral ischemia and reperfusion, does not attenuate the ischemic damage.     

三七三醇皂苷对脑缺血再灌注大鼠的保护作用

目的 通过对局灶性脑缺血大鼠不同再灌注时段的动态观察．探讨三七三醇皂苷(PTS)对大鼠局灶性脑缺血／再灌注动物模型的神经行为学和脑梗死体积的保护作用。方法 采用改良的线栓法制备大脑中动脉阻塞(MACO)2h、再灌注不同时间段(3h、6h、12h、24h、48h、72h、7d)的大鼠短暂局灶性脑缺血模型。动物随机分假手术组、生理盐水对照组、三七三醇皂苷(PTS)组。用Zea Longa5分制评分和TTC染色法评价神经行为学和脑梗死体积。结果 神经行为学评分除72h组有明显改善外．其余各组与生理盐水对照组比较无显著性差异。脑梗死体积除再灌注3h、6h外．其余各组与生理盐水组比较差异均有显著性意义。结论 三七三醇皂苷对大鼠局灶性脑缺血及再灌注损伤有一定的保护作用。     

Dose-dependent effects of procyanidin on nerve growth factor expression following cerebral ischemia/ reperfusion injury in rats★

BACKGROUND： Recently, grape seed procyanidin （GSP） has been shown to be exhibit antioxidant effects, effectively reducing ischemia/reperfusion injury and inhibiting brain cell apoptosis. OBJECTIVE： To study the effects of GSP on nerve growth factor （NGF） expression and neurological function following cerebral ischemia/reperfusion injury in rats. DESIGN： Randomized controlled study based on SD rats. SETTING： Weifang Municipal People＇s Hospital. MATERIALS： Forty-eight healthy adult SD rats weighing 280-330 g and irrespective of gender were provided by the Experimental Animal Center of Shandong University. GSP derived from grape seed was a new high-effective antioxidant provided by Tianjin Jianfeng Natural Product Researching Company （batch number： 20060107）. Rabbit-anti-rat NGF monoclonal antibody was provided by Beijing Zhongshan Biotechnology Co., Ltd., and SABC immunohistochemical staining kit by Wuhan Boster Bioengineering Co., Ltd. METHODS： The present study was performed in the Functional Laboratory of Weifang Medical College from April 2006 to January 2007. Forty-eight SD rats were randomly divided into the sham operation group, ischemia/reperfusion group, high-dose GSP （40 mg/kg） group, or low-dose GSP （10 mg/kg） group （n = 12 per group）. Ischemia/reperfusion injury was established using the threading embolism method of the middle cerebral artery. Rats in the ischemia/reperfusion model group were given saline injection （2 mL/kg i.p.） once daily for seven days pre-ischemia/reperfusion, and once more at 15 minutes before reperfusion. Rats in the high-dose and low-dose GSP groups were injected with GSP （20 or 5 mg/mL i.p., respectively, 2 mL/kg） with the same regime as the ischemia/reperfusion model group. The surgical procedures in the sham operation group were as the same as those in the ischemia/reperfusion model group, but the thread was approximately 10 mm long, thus, the middle cerebral artery was not blocked. MAIN OUTCOME MEASURES： NGF expression in the     

川芎嗪在不同时期对脑缺血再灌注后MMP-9表达的影响

目的:研究川芎嗪注射液在缺血前和(或)缺血中处理对脑缺血再灌注后脑组织基质金属蛋白酶-9(MMP- 9)表达的影响。方法:对60只健康SD大鼠进行分组,采用线栓法制作大鼠大脑中动脉闭塞局灶性脑缺血再灌注模型, 于大鼠脑缺血前、缺血中以及两者同时经腹腔注射川芎嗪进行治疗,然后观察再灌注12小时后脑梗死体积,并采用免 疫组化法检测MMP-9的变化。结果:再灌注12小时后,川芎嗪缺血前治疗组、缺血中治疗组、缺血前和缺血中联合治疗 组的脑梗死的体积较对照组明显减小,MMP-9的表达明显低于对照组,P值均<0．05,以川芎嗪缺血前和缺血中联合治 疗的作用最强。结论:川芎嗪能明显地减小脑梗死的体积,降低MMP-9的表达,发挥脑保护的作用,尤以川芎嗪在缺血 前和缺血中的联合治疗效果明显。     

脑缺血再灌流脑微血管损害及u-PA表达的实验研究

目的探讨脑缺血再灌流后继发的脑水肿、出血的发生机制。方法应用光镜、透射电镜、免疫组织化学、显微镜－计算机图像分析等技术，观察大鼠局部脑缺血２小时再灌流不同时间，脑微血管结构、Ⅳ型胶原抗原及尿激酶型纤溶酶原激活物（ｕ－ＰＡ）表达。结果局部脑缺血再灌流２４小时，缺血侧ＭＣＡ区脑微血管外细胞间质水肿最严重，基底膜节段性溶解、缺损，有红细胞漏出，微血管壁及管外细胞间质ｕ－ＰＡ大量表达达高峰，同时微血管基底膜Ⅳ型胶原抗原减少。随再灌流时间延长，微血管基底膜损害加重，Ⅳ型胶原抗原逐渐消失，ｕ－ＰＡ表达减少。结论脑缺血再灌流后脑微血管结构损害是导致脑水肿、出血的主要病理基础，而脑微血管壁和管外细胞间质ｕ－ＰＡ表达可能是引起微血管损害的主要机制之一。     

D1和D2受体拮抗剂对乙灶性脑缺血梗塞体积及脑血流的影响

目的 研究多巴胺（ＤＡ）Ｄ１受体拮抗剂ＳＣＨ－２３３９０和Ｄ２受体拮抗剂Ｅｔｉｃｌｏｐｒｉｄｅ对可逆性乙灶性脑缺血梗塞体积及皮层半暗带脑血流的影响。方法 采用激光多普勒脑血流计测量大鼠可逆性乙灶性脑缺血各时相皮层半暗带脑血流,并于缺血后２４小时断头取脑切片,ＴＴＣ染色,计算机图样分析系统测量脑梗塞体积。结果 Ｄ１受体拮抗剂ＳＣＨ－２３３９０可明显缩小局灶性脑缺血梗塞体积,改善缺血期各时相皮层半暗带     

Cervical sympathetic trunk transection affects inducible nitric oxide synthase expression in rat hippocampus following focal cerebral ischemia/reperfusion injury

BACKGROUND： The stellate ganglion block （SGB） plays a protective role in focal cerebral ischemia/reperfusion injury. The human SGB can be simulated by transection of the cervical sympathetic trunk （TCST） in rats. OBJECTIVE： To observe the effects of TCST on inducible nitric oxide synthase （iNOS） levels and cerebral infarct volume in the hippocampus of rats with cerebral ischemia/reperfusion injury, and to analyze the mechanism of action. DESIGN, TIME AND SETTING： A completely randomized, controlled, neuropathological experiment was performed at the Institute of Neurological Disease, Taihe Hospital, Yunyang Medical College between March and September 2006. MATERIALS： A total of 93 Wistar rats, aged 1718 weeks, of either gender, were used for this study. 2, 3, 5-triphenyl tetrazolium chloride was purchased from Changsha Hongyuan Biological Reagent Company China. Rabbit iNOS antibody and goat anti-rabbit IgG antibody were the products of Wuhan Boster Biological Reagent Co., Ltd., China. METHODS： Ten rats were randomly selected for the sham-operated group. Cerebral ischemia/reperfusion injury was induced by middle cerebral artery occlusion （MCAO） using the suture method in the remaining rats. Forty successful rat models were randomly and equally divided into the following two groups： （1） TCST group： subsequent to TCST, MCAO was performed for 2 hours, followed by 24 hours reperfusion; （2） model group： rats underwent experimental procedures similar to the TCST group, with the exception of TCST. Rats in the sham-operated group were subjected to experimental procedures similar to the model group; however, the thread was only introduced to a depth of 10 mm. MAIN OUTCOME MEASURES： Following 24 hours of reperfusion, functional neurological deficits were scored. Brain tissue sections from ten rats of each group were used to measure cerebral infarct volume by TTC staining. Hippocampal tissue sections of an additional ten rats from each group were used to detect iNOS levels using the s     

Effects of low molecular weight heparin-superoxide dismutase conjugate on serum levels of nitric oxide, glutathione peroxidase, and myeloperoxidase in a gerbil model of cerebral ischemia/reperfusion injury

BACKGROUND： Several studies have demonstrated that low molecular weight heparin-superoxide dismutase （LMWH-SOD） conjugate may exhibit good neuroprotective effects on cerebral ischemia/reperfusion injury though anticoagulation, decreasing blood viscosity, having anti-inflammatory activity, and scavenging oxygen free radicals. OBJECTIVE： To investigate the intervention effects of LMWH-SOD conjugate on serum levels of nitric oxide （NO）, glutathione peroxidase （GSH-Px）, and myeloperoxidase （MPO） following cerebral ischemia/reperfusion injury. DESIGN, TIME AND SETTING： A randomized, controlled, and neurobiochemical experiment was performed at the Institute of Biochemical Pharmacy, School of Pharmaceutical Sciences, Shandong University between April and July 2004. MATERIALS： A total of 60 Mongolian gerbils of either gender were included in this study. Total cerebral ischemia/reperfusion injury was induced in 50 gerbils by occluding bilateral common carotid arteries. The remaining 10 gerbils received a sham-operation （sham-operated group）. Kits of SOD, NO, and MPO were sourced from Nanjing Jiancheng Bioengineering Institute, China. LMWH, SOD, and LMWH-SOD conjugates were provided by Institute of Biochemistry and Biotechnique, Shandong University, China. METHODS： Fifty successful gerbil models of total cerebral ischemia/reperfusion injury were evenly randomized to five groups： physiological saline, LMWH-SOD, SOD, LMWH ＋ SOD, and LMWH. At 2 minutes prior to ischemia, 0.5 mL/65 g physiological saline, 20 000 U/kg LMWH-SOD conjugate, 20 000 U/kg SOD, a mixture of SOD （20 000 U/kg） and LMWH （LMWH dose calculated according to weight ratio, LMWH： SOD = 23.6：51）, and LMWH （dose as in the LMWH ＋ SOD group） were administered through the femoral artery in each above-mentioned group, respectively. MAIN OUTCOME MEASURES： Serum levels of NO, MPO, and GSH-Px. RESULTS： Compared with 10 sham-operated gerbils, the cerebral ischemia/reperfusion injury gerbils exhibited decreased s