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1.
目的:探讨梓醇对缺血再灌注大鼠脑损伤后的保护作用.方法:采用传统大脑中动脉阻塞(MCAO)方法制备大鼠局灶性缺血模型,根据随机数字表法将SD大鼠分为MCAO组、对照组(vehicle组)及梓醇处理组(catalpol组),缺血再灌注48 h后观察各组大鼠神经功能学评分和脑梗死容积.分别于术前、术后6h、24 h、48 h取大鼠脑组织样本,检测匀浆中谷胱甘肽过氧化物酶(GSH-PX)和丙二醛(MDA)的变化情况.结果:与vehicle组和MCAO组相比,catalpol处理组神经功能学评分降低(P<0.05);其梗死容积较小(P<0.05).组织匀浆结果显示catalpol处理组脑匀浆中GSH-PX活力升高,MDA含量下降(P<0.05).结论:梓醇可能通过降低脑内自由基水平、控制脂质过氧化程度,对缺血再灌注引起的大鼠脑损伤产生神经保护作用.  相似文献   

2.
目的:探讨三七总皂苷(PNS)对缺血再灌注损伤后大鼠大脑皮层组织丙二醛(MDA)的含量、谷胱甘肽过氧化物酶(GSH-PX)的活性的影响.方法:采用线栓法制备大鼠大脑中动脉局灶缺血再灌注模型,选用Wistar雄性大鼠(54只)随机分成3组,即:假手术组(12只)、缺血再灌注组(24只)、三七总皂苷治疗组(18只);再根据灌注时间不同分为再灌注l0h、12h、24h组,每组是8只.缺血时间为90min.各组动物给药方法:三七总皂苷治疗组(PNS组)腹腔注射1%PNS(50mg/kg),每天一次,持续10天;假手术组和缺血再灌注模型组腹腔注射与PNS组等体积的生理盐水10天,各组于术前1h再注射1次.进行HE染色观察脑皮层组织形态病理学变化;硫代巴比妥酸比色法检测MDA的含量;二硫双硝基苯甲酸法检测GSH-PX的活性.结果:缺血再灌注组GSH-PX的活性降低(P<0.05),MDA的含量升高(P< 0.05);PNS治疗组GSH-PX的活性明显增强(P<0.05),MDA的含量明显下降(P<0.05).结论:PNS可能通过增加GSH-PX的活性和减少MDA的含量来拮抗缺血再灌注损伤后脑组织的脂质过氧化,发挥脑组织的保护作用.  相似文献   

3.
目的:探讨丹酚酸A对大鼠脑缺血/再灌注(cerebral ischemia/reperfusion,CI/R)损伤及抗氧化酶活性的影响。方法:采用大鼠脑中动脉闭塞(middle cerebral arteryocclusion,MCAO)2 h再灌注24 h模型。实验终末,检测脑梗死面积,脑水肿以及评价神经功能损伤,并进一步分析脑组织中三种抗氧化酶的活性水平。结果:与模型组相比,丹酚酸A组大鼠脑梗死面积显著减少(P0.05),水肿程度显著减轻(P0.05),神经功能学评分显著下降(P0.05)。模型组再灌注24 h后,SOD,GSH-PX及CAT活性显著下降(P0.05);丹酚酸A组SOD,GSH-PX及CAT活性则显著升高(P0.05)。结论:丹酚酸A对大鼠CI/R损伤具有保护作用,可能与CI/R损伤时的脑组织SOD,GSH-PX及CAT活性显著升高相关。  相似文献   

4.
目的:观察孕酮(PROG)对大鼠局灶性脑缺血/再灌注损伤后的神经保护作用,并探讨其作用机制。方法:120只雄性SD大鼠随机分为:假手术组、大脑中动脉栓塞(MCAO)组和PROG+MCAO组(n=40)。线栓法建立大鼠右侧MCAO模型,PROG+MCAO组于建模型前30 min按8 mg/kg腹腔内注射PROG。大鼠脑缺血2 h再灌注0、24、48、72 h,通过Longa评分标准进行神经功能缺陷评分;实时荧光定量聚合酶链反应技术检测大鼠脑组织中双孔道结构域钾离子通道3(TASK3)mRNA的表达。结果:PROG(8 mg/kg)可显著降低大鼠脑缺血2 h再灌注24、48、72 h时的神经功能缺陷评分(P0.05)。与假手术组相比,MCAO组再灌注各时间点脑组织TASK3 mRNA的表达均显著降低(P0.05);与MCAO组相比,PROG+MCAO组再灌注各时间点大鼠脑组织中TASK3 mRNA的表达均显著增多(P0.05)。结论:PROG可改善局灶性脑缺血/再灌注损伤后大鼠神经功能缺陷症状,其作用机制可能与上调脑组织中TASK3 mRNA的表达有关。  相似文献   

5.
目的:研究L-丝氨酸对大鼠脑缺血/再灌注损伤保护作用的时间窗,并对其作用机制进行初探。方法:SD雄性大鼠随机分为假手术组、对照组、L-丝氨酸3h治疗组、6h治疗组、12h治疗组、24h治疗组。采用大脑中动脉栓塞(MCAO)建立大鼠局灶性脑缺血模型,2h后拔出栓线形成再灌注,各组分别于术后相应的时间点给予L-丝氨酸200mg/kg腹腔注射2次,对照组注射等剂量的生理盐水,所有动物再灌注后48h观测神经行为学评分、脑梗死体积。另取假手术组、对照组、L-丝氨酸6h治疗组,分别测定MCAO后脑内超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量,炎症细胞因子TNF-α、IL-6水平以及观察细胞超微结构改变。结果:与对照组相比,术后3h、6h给予L-丝氨酸治疗能显著降低大鼠神经行为学评分,减少脑梗死体积(P〈0.01或P〈0.05),12h仅能降低神经行为学评分(P〈0.05),而24h与对照组间均无差异;L-丝氨酸能提高MCAO后脑内SOD活性,降低MDA以及TNF-α、IL-6的水平,同时改善细胞超微结构。结论:在一定时间窗内,L-丝氨酸对大鼠MCAO具有明显的神经保护作用,其机制可能与降低氧自由基损伤,减轻炎症反应有关。  相似文献   

6.
目的:探讨氢饱和生理盐水对大鼠脑缺血再灌注损伤模型的治疗效果及可能的作用机制。方法:SD大鼠(250-300g)随机分为3组(n=20):假手术组(Sham组),缺血再灌注损伤模型组(I/R组),氢饱和盐水治疗组(HS组)。采用大鼠线栓法右侧中动脉栓塞模型(MCAO模型),于模型90 min时拔出线栓进行再灌注,再灌注同时,I/R组腹腔给予生理盐水10 m L/kg,HS组腹腔给予氢饱和生理盐水10 m L/kg。24 h后,对各组大鼠进行神经功能缺陷评分。断头取脑后,TTC染色法检测脑组织梗死体积(n=10)。选取缺血半暗带处大脑皮层组织进行相关指标测定(n=10)。HE染色观察大鼠缺血半暗带脑组织形态结构,测定缺血半暗带区域氧化应激反应,选取指标为SOD,MDA;并观察缺血半暗带区域炎症反应,利用Elisa方法测定该处TNF-α,IL-6含量。结果:TTC染色证实,右侧MCAO明显诱导大鼠脑局灶性缺血(P0.05)。与I/R组相比,HS组明显降低脑梗死体积(P0.05),显著降低大鼠神经功能缺陷评分(P0.05)。与I/R组相比,氢饱和生理盐水治疗后,很好的保持了缺血半暗带区域细胞结构完整性,明显提高了SOD含量(P0.05),有效降低了MDA水平(P0.05),并且减轻了炎症因子TNF-α,IL-6含量(P0.05)。结论:氢饱和生理盐水可有效的治疗脑缺血再灌注损伤,其机制可能涉及氢气在缺血半暗带区域的选择性的抗氧化应激作用,以及抗炎症反应。  相似文献   

7.
目的:探讨丹酚酸A对大鼠脑缺血/再灌注(cerebral ischemia/reperfusion,CI/R)损伤及抗氧化酶活性的影响。方法:采用大鼠脑中动脉闭塞(middle cerebral arteryocclusion,MCAO)2 h再灌注24 h模型。实验终末,检测脑梗死面积,脑水肿以及评价神经功能损伤,并进一步分析脑组织中三种抗氧化酶的活性水平。结果:与模型组相比,丹酚酸A组大鼠脑梗死面积显著减少(P〈0.05),水肿程度显著减轻(P〈0.05),神经功能学评分显著下降(P〈0.05)。模型组再灌注24 h后,SOD,GSH-PX及CAT活性显著下降(P〈0.05);丹酚酸A组SOD,GSH-PX及CAT活性则显著升高(P〈0.05)。结论:丹酚酸A对大鼠CI/R损伤具有保护作用,可能与CI/R损伤时的脑组织SOD,GSH-PX及CAT活性显著升高相关。  相似文献   

8.
目的:探讨毛蕊异黄酮抗脑缺血再灌注损伤的作用是否与抑制calpain-1的表达有关。方法:将SD大鼠随机分为假手术组、模型组以及药物组,采用线栓法建立大鼠大脑中动脉阻断(MCAO)模型,于缺血再灌注前30 min腹腔注射给予20 mg/kg毛蕊异黄酮或等体积的溶剂。再灌注24 h后,行神经功能学评分、脑梗死面积以及神经元凋亡检测;再灌注12 h、24 h时,采用免疫组化和蛋白印迹技术检测大鼠脑皮层calpain-1的表达。结果:与假手术组大鼠比较,MCAO模型组大鼠再灌注24 h后神经功能学评分、梗死面积、神经元凋亡率及calpain-1的表达均明显升高(P0.05),而毛蕊异黄酮能够降低模型组大鼠再灌注24 h后神经功能学评分、梗死面积、神经元凋亡率以及calpain-1的表达(P0.05)。结论:毛蕊异黄酮可能通过抑制calpain-1的表达发挥抗脑缺血再灌注损伤作用。  相似文献   

9.
五味子醇甲(Schisandra A, Sch A)是五味子中具有生物活性的木脂素化合物,其神经保护作用已在多种神经系统疾病动物模型中得到验证。然而,五味子醇甲是否能通过影响大鼠脑缺血半影区神经元自噬活性对脑缺血再灌注大鼠模型产生神经保护作用,尚缺乏系统研究。为探究Sch A对大鼠脑卒中后神经损伤及缺血半影区神经元自噬活性的影响,本研究将90只SD雄性大鼠随机分为假手术(Sham)组、模型组(MCAO)、Sch A低剂量组(40μg/kg)、Sch A中剂量组(80μg/kg)、Sch A高剂量组(160μg/kg),每组18只。线栓法制备大鼠大脑中动脉梗塞(middle cerebral artery occlusion,MCAO)模型,脑缺血持续90 min后进行再灌注,立即侧脑室给药,1/d,连续给药7 d。各组分别取6只大鼠进行神经功能评分后,取脑进行TTC染色检测脑梗死体积。另有6只大鼠取缺血半影区脑组织,通过Western印迹检测自噬相关蛋白质Beclin1、LC3-Ⅱ的表达水平。剩余6只大鼠脑组织用于免疫荧光双标,对Sch A改变的自噬活性进行细胞表达定位。研究结果显示,MCAO组大鼠脑梗死体积及神经功能损伤评分均显著高于Sham组(P0.05),且Beclin1及LC3-Ⅱ的表达显著增加(P0.05)。各Sch A治疗组大鼠脑梗死体积较未给药组显著减少(P0.05),神经功能损伤得到明显改善(P0.05)。同时,Sch A给药组Beclin1及LC3蛋白质表达水平明显升高(P0.05),且免疫荧光双标显示该自噬活性改变主要呈现于神经元。以上结果表明,Sch A可显著减轻大鼠脑缺血再灌注损伤,该神经保护作用与其提高缺血半影区神经元自噬活性密切相关。  相似文献   

10.
目的:探索糖原合成激酶3β(GSK-3β)在电针预处理诱导的脑缺血再灌损伤保护中的作用.方法:60只雄性SD大鼠随机分成5组(n=12):假手术(Sham)、大脑中动脉栓塞组(MCAO)、电针预处理组(EA)、电针预处理加LY294002组(EA+LY)、电针预处理加溶剂组(vehicle);通过梗死面积及Garcia评分评价脑损伤程度,通过Western Blot检测GSK-3β活性.结果:与MCAO组相比,EA组梗死容积减少,Garcia评分改善(P<0.05);与vehicle组相比,EA+LY组梗死容积增加,Garcia评分降低(P<0.05);与MCAO组相比再灌注后2小时EA组GSK-3β磷酸化水平升高(P<0.05);与EA组相比EA+LY组GSK-3β3磷酸化水平降低(P<0.05).结论:电针预处理通过促进缺血再灌注后GSK-3β的磷酸化发挥脑保护作用.  相似文献   

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It has now been over twenty years since a novel herpesviral genome was identified in Kaposi's sarcoma biopsies. Since then, the cumulative research effort by molecular biologists, virologists, clinicians, and epidemiologists alike has led to the extensive characterization of this tumor virus, Kaposi's sarcoma-associated herpesvirus(KSHV; also known as human herpesvirus 8(HHV-8)), and its associated diseases. Here we review the current knowledge of KSHV biology and pathogenesis, with a particular emphasis on new and exciting advances in the field of epigenetics. We also discuss the development and practicality of various cell culture and animal model systems to study KSHV replication and pathogenesis.  相似文献   

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正Dear Editor,In December 2019, a novel human coronavirus caused an epidemic of severe pneumonia(Coronavirus Disease 2019,COVID-19) in Wuhan, Hubei, China(Wu et al. 2020; Zhu et al. 2020). So far, this virus has spread to all areas of China and even to other countries. The epidemic has caused 67,102 confirmed infections with 1526 fatal cases  相似文献   

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Curcumin is the yellow pigment of turmeric that interacts irreversibly forming an adduct with thioredoxin reductase (TrxR), an enzyme responsible for redox control of cell and defence against oxidative stress. Docking at both the active sites of TrxR was performed to compare the potency of three naturally occurring curcuminoids, namely curcumin, demethoxy curcumin and bis-demethoxy curcumin. Results show that active sites of TrxR occur at the junction of E and F chains. Volume and area of both cavities is predicted. It has been concluded by distance mapping of the most active conformations that Se atom of catalytic residue SeCYS498, is at a distance of 3.56 from C13 of demethoxy curcumin at the E chain active site, whereas C13 carbon atom forms adduct with Se atom of SeCys 498. We report that at least one methoxy group in curcuminoids is necessary for interation with catalytic residues of thioredoxin. Pharmacophore of both active sites of the TrxR receptor for curcumin and demethoxy curcumin molecules has been drawn and proposed for design and synthesis of most probable potent antiproliferative synthetic drugs.  相似文献   

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The young pistils in the melanthioid tribes, Hewardieae, Petrosavieae and Tricyrteae, are uniformly tricarpellate and syncarpous. They lack raphide idioblasts. All are multiovulate, with bitegmic ovules. The Petrosavieae are marked by the presence of septal glands and incomplete syncarpy. Tepals and stamens adhere to the ovary in the Hewardieae and the Petrosavieae but not in the Tricyrteae. Two vascular bundles occur in the stamens of the Hewartlieae and Tricyrtis latifolia. Ventral bundles in the upper part of the ovary of the Hewardieae are continuous with compound septal bundles and placental bundles in the lower part. Putative ventral bundles occur in the alternate position in the Tricyrteae and putative placental bundles in the opposite. position in the Petrosavieae. The dichtomously branched stigma in each carpel of the Tricyrteae is supplied by a bifurcated dorsal bundle.  相似文献   

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Microbial resistance to antibiotics is an unresolved global concern, which needs urgent and coordinated action. One of the guidelines of the Centers for Disease Control and Preventions (CDC) to combat antibiotic resistance is the development of new antibiotics to treat drug-resistant bacteria. In our effort to find new antibiotics, we report the synthesis and antimicrobial studies of 30 new pyrazole derivatives. These novel molecules have been synthesized by using readily available starting materials and benign reaction conditions. Some of these molecules have shown activity with MIC values as low as 0.78?µg/mL against four bacterial strains; Staphylococcus aureus, methicillin-resistant S. aureus, Bacillus subtilis, and Acinetobacter baumannii. Furthermore, active molecules are non-toxic to mammalian cell line.
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Cyclin-dependent kinases (CDKs) and Polo-like kinases (PLKs) play key role in the regulation of the cell cycle. The aim of our study was originally the further development of our recently discovered polo-like kinase 1 (PLK1) inhibitors. A series of new 2,4-disubstituted pyrimidine derivatives were synthesized around the original hit, but their PLK1 inhibitory activity was very poor. However the novel compounds showed nanomolar CDK9 inhibitory activity and very good antiproliferative effect on multiple myeloma cell lines (RPMI-8226).  相似文献   

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