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1.
目的:研究人参二醇组皂甙(PDS)对大鼠脑缺血-再灌注海马超微结构、皮层和海马一氧化氮合酶(NOS)活性的影响。方法:双侧颈总动脉阻断和再灌注建立脑缺血-再灌流模型,电镜技术和NADPH-d组织化学技术。结果:电镜观察可见,缺血30min再灌注2h大鼠海马超微结构发生缺血性病理改变,PDS对缺血脑组织病理变化有显著保护作用。NADPH-d组织化学实验表明,脑缺血15min和再灌注24h后,皮层及海马NOS阳性细胞数目显著增多,PDS可显著抑制此增多。结论:PDS可通过降低脑内NOS的活性,减少脑缺血-再灌注过程中NO的产生,对缺血脑组织产生保护作用  相似文献   

2.
电针对脑缺血神经元凋亡影响的形态学研究   总被引:12,自引:0,他引:12  
为了探讨针刺治疗“脑卒中”的机制,本研究以大鼠一侧大脑中动脉栓塞后再灌注为动物模型,分别以TUNEL法和PI染色法观察电针改善脑缺血性神经元凋亡的情况。结果显示:①局灶性脑缺血能诱导神经元凋亡:缺血侧凋亡神经元数目明显多于对照侧,差异非常显著;②电针能明显抑制神经元凋亡:电针治疗组缺血侧梗塞区凋亡神经元数目明显减少。本文表明电针能抑制脑缺血性神经元凋亡。  相似文献   

3.
应用RNA印迹分析和亚硝酸盐含量测定检查脂多糖(LPS)对大鼠血管平滑肌细胞(VSMC)一氧化氮合酶(NOS)基因表达及NO合成的影响,用3H-TdR参入实验观察LPS对细胞DNA合成的影响.结果表明,LPS在诱导VSMCiNOSmRNA表达和促进NO合成的同时,抑制VSMCDNA合成.证明LPS的作用与其浓度和作用时间有关  相似文献   

4.
应用RNA迷分析和亚硝酸盐含量测定检查脂多糖(LPS)对大鼠血管平滑肌细胞(VSMC)一氧化氮合酶(NOS)基因表达及NO合成的影响,用T3H-TdR参入实验观察LPS对细胞DNA合成的影响,结果表明,LPSD 诱导VSMCiNOSmRNA表达和促进NO合成的同时,抑制VSMCDNA合成,证明LPS的作用与其浓度和作用时间有关。  相似文献   

5.
通过RNA印迹分析和亚硝酸盐含量测定检查TNF-α、IL-1β和LPS对大鼠血管平滑肌细胞(VSMC)诱导型一氧化氮合酶(iNOS)基因表达及NO生成的影响.结果表明,TNF-α、IL-1β和LPS均能显著诱导VSMCiNOS基因表达和促进NO生成,其作用强度与浓度和作用时间有关;双因素(TNF-α+LPS,LPS+IL-1β)对诱导iNOS基因表达及NO生成产生协同作用.PolymyxinB和地塞米松可部分抑制TNF-α对iNOS基因表达的诱导作用及NO生成  相似文献   

6.
本文在大鼠双侧颈总动脉闭塞的不完全性脑缺血模型上,观察了尼莫地平在脑缺血中对一氧化氮( N O) 和自由基的影响。发现尼莫地平显著降低脑缺血大鼠血清中乳酸脱氢酶( L D H) 活性,丙二醛( M D A)含量,增加 N O 含量。结果提示:尼莫地平对脑缺血大鼠的保护作用可能与其抗脂质过氧化及增加 N O 有关。  相似文献   

7.
报道了内皮素A型受体反义寡聚核苷酸(ODNs)对大鼠血管平滑肌细胞(VSMC)增殖及内皮素受体基因表达的影响.~3H-TdR参入结果显示,内皮素A型受体反义ODNs处理细胞可显著抑制内皮素诱导的VSMC的DNA合成,反转录-PCR及受体结合实验结果表明,ODNs的上述作用与降低VSMC内皮素A型受体基因表达活性有关.  相似文献   

8.
止血带休克时主动脉舒缩功能与一氧化氮合酶活性的关系   总被引:5,自引:0,他引:5  
目的:为探讨止血带休克发生过程中血管舒缩功能的改变及意义,以及与血管一氧化氮(NO)产生的关系。方法:采用Rosenthal方法复制大鼠止血带休克(ToS)模型,分别测定对照组和ToS组大鼠血浆中,主动脉孵育液中亚硝酸盐(NO-2)含量及主动脉组织中cGMP含量,一氧化氮合酶(NOS)活性,同时观察了主动脉血管环舒缩功能的改变。结果:ToS大鼠离体主动脉环对去甲肾上腺素的反应性降低;其血浆和主动脉孵育液中NO-2明显增加;主动脉cGMP含量增多;主动脉血管总NOS活性加强,其中主要是诱导型NOS(iNOS)活性增加。结论:ToS大鼠主动脉NOS活性加强,产生NO增多,造成血管低反应性。  相似文献   

9.
目的:研究人参二醇组皂甙(PDS)对大鼠脑缺血-再灌注海马超微结构、皮层和海马一氧化氮合酶(DNO)活性的影响。方法:双侧颈总动脉阻断和再灌注建立脑缺血-再灌流模型,电镜技术和NADPH-d组织化学技术。结果:电镜观察可见,缺血30min再灌注2h大鼠海马超微结构发生缺血性病理改变,PDS对缺血脑组织病变化有显著保护作用。NADPH-d组织化学实验表明,脑缺血15min和再灌注24h后,皮层海马N  相似文献   

10.
目的:观测流体剪切应力对血管内皮细胞NO合成酶(nitric oxidesynthase,NOS)活性的影响并探讨其发生机制。方法:采用Griess 方法测定不同流体剪切应力作用下血管内皮细胞中NOS活性的变化;并观测多种NOS干预物质对这种变化的影响。结果:剪切应力显著提高血管内皮细胞中NOS活性;地塞米松(dexamethasone)实验表明,剪切应力这种作用主要是通过对结构型NOS活性的增强实现的,且具有明显的剂量和时间依赖性;放线菌酮(cycloheximide)非特异性地抑制细胞中NOS酶蛋白合成,但cycloheximide 处理组中受剪切应力作用细胞NOS活性仍显著高于其对照细胞,仅升高幅度明显降低。A23187 处理后细胞中NOS活性升高约达2 倍,其中剪切应力作用细胞的NOS活性显著高于其对照,但这种变化程度亦较A23187 未处理组明显减小。结论:剪切应力显著提高血管内皮细胞eNOS活性:eNOS酶蛋白合成增加和细胞内Ca2+ 浓度的升高在剪切应力对血管内皮细胞NOS活性的调节机制中具有重要意义  相似文献   

11.
电针对局灶性脑缺血大鼠脑内神经生长因子受体trkA的影响   总被引:12,自引:0,他引:12  
神经生长因子对神经元凋亡有拮抗作用,其作用方式是通过特异性受体——trkA实现。为了探讨针刺对内源性抗凋亡因素的调节作用。本研究用大鼠局灶性脑缺血再灌注模型,应用免疫组织化学方法观察缺血再灌注时trkA的变化及针刺对trkA的影响。结果发现:缺血组对照侧大脑皮层偶见散在trkA免疫阳性神经元,缺血侧大脑皮层trkA阳性神经元与对照侧相比,显微镜下见无显著性差异。电针组缺血侧大脑皮层见大量trkA免疫反应阳性神经元,主要分布于半影区,与对照侧及未电针的缺血侧相比,显微镜下见阳性神经元数目有差异。结果提示:电针可以诱导脑缺血时神经营养因子受体表达,调动机体内抗凋亡因素的作用。  相似文献   

12.
Previous studies have shown that intermittent hypobaric hypoxia (IH) preconditioning protected neurons survival from brain ischemia. However, the mechanism remains to be elucidated. The present study explored the role of nitric oxide (NO) in the process by measuring the expression of NO synthase (NOS) and NO levels. Male Wistar rats (100) were randomly assigned into four groups: sham group, IH?+?sham group, ischemia group and IH?+?ischemia group. Rats for IH preconditioning were exposed to hypobaric hypoxia mimicking 5000 m high-altitude (PB?=?404 mmHg, PO2?=?84 mmHg) 6 h/day, once daily for 28 days. Global brain ischemia was established by four-vessel occlusion that has been created by Pulsinelli. Rats were sacrificed at 7th day after the ischemia for neuropathological evaluation by thionin stain. In addition, the expression of neuronal NOS (nNOS), inducible NOS (iNOS), and NO content in the hippocampal CA1 subfield were measured at 2nd day and 7th day after the ischemia. Results revealed that global brain ischemia engendered delayed neuronal death (DND), both nNOS and iNOS expression up-regulated, and NO content increased in the hippocampal CA1 subfield. IH preconditioning reduced neuronal injury induced by the ischemia, and prevented the up-regulation of NOS expression and NO production. In addition, l-NAME?+?ischemia group was designed to detect whether depressing NO production could alleviate the DND. Pre-administration of l-NAME alleviated DND induced by the ischemia. These results suggest that IH preconditioning plays a protective role by inhibiting the over expression of NOS and NO content after brain ischemia.  相似文献   

13.
新生大鼠缺血缺氧后脑内一氧化氮合酶的动态表达   总被引:3,自引:0,他引:3  
实验采用生后14天Wistar大鼠缺血缺氧(HI)动物模型。用免疫组织化学方法观察HI复苏(HI/R0后前脑一氧化氮合酶动态表达。结果显示;神经元一氧化氮合酶(nNOS)阳性神经元主要分布于新生大鼠大脑皮层的Ⅲ-Ⅳ层。尾状核,隔核及嗅结节,HI/R早期其表达水平无明显变化;复苏48小时及5天后,可分别在右侧大脑顶皮层或右侧大脑顶皮层和尾状核区出现梗塞灶,该区nNOS阳性神经元明显减少,而诱导型一氧化氮合酶(iNOS)阳性细胞在HI/R后12小时始现于损伤侧的侧脑室;随时间的推移在损伤侧缰核,皮层,尾状核以及丘脑背外侧核,丘脑腹侧核可见iNOS阳性细胞逐渐增多并染色加深,用识别单核巨噬细胞的克隆ED1单克隆抗体检测可见ED1阳性细胞出现的时间和在脑区的分布与iNOS阳性细胞相似,本实验提示,在局灶性脑缺血缺氧早期,脑内NO的释放不依赖于nNOS阳性神经元或iNOS阳性细胞,而在局灶性脑缺血缺氧晚期,iNOS阳性细胞产生的NO可能参与了脑损伤的过程。  相似文献   

14.
Luo CX  Zhu XJ  Zhou QG  Wang B  Wang W  Cai HH  Sun YJ  Hu M  Jiang J  Hua Y  Han X  Zhu DY 《Journal of neurochemistry》2007,103(5):1872-1882
Nitric oxide (NO), a free radical with signaling functions in the CNS, is implicated in some developmental processes, including neuronal survival, precursor proliferation, and differentiation. However, neuronal nitric oxide synthase (nNOS) -derived NO and inducible nitric oxide synthase (iNOS) -derived NO play opposite role in regulating neurogenesis in the dentate gyrus after cerebral ischemia. In this study, we show that focal cerebral ischemia reduced nNOS expression and enzymatic activity in the hippocampus. Ischemia-induced cell proliferation in the dentate gyrus was augmented in the null mutant mice lacking nNOS gene (nNOS−/−) and in the rats receiving 7-nitroindazole, a selective nNOS inhibitor, after stroke. Inhibition of nNOS ameliorated ischemic injury, up-regulated iNOS expression, and enzymatic activity in the ischemic hippocampus. Inhibition of nNOS increased and iNOS inhibitor decreased cAMP response element-binding protein phosphorylation in the ipsilateral hippocampus in the late stage of stroke. Moreover, the effects of 7-nitroindazole on neurogenesis after ischemia disappeared in the null mutant mice lacking iNOS gene (iNOS−/−). These results suggest that reduced nNOS is involved in ischemia-induced hippocampal neurogenesis by up-regulating iNOS expression and cAMP response element-binding protein phosphorylation.  相似文献   

15.
Pei DS  Song YJ  Yu HM  Hu WW  Du Y  Zhang GY 《Journal of neurochemistry》2008,106(4):1952-1963
Nitric oxide (NO), synthesized from l -arginine by NO synthases, is a small endogenous free radical with multiple functions. The c-Jun N-terminal kinase (JNK) signaling pathway plays a critical role in mediating apoptosis in cerebral ischemia and reperfusion. In this study, we found that the NO donor sodium nitroprusside (SNP) can decrease the damage of hippocampal neurons induced by cerebral ischemia and reperfusion. Our current study demonstrates that SNP can suppress the phosphorylation of JNK3 by suppressing the increased S-nitrosylation of JNK3 induced by cerebral ischemia and reperfusion. In contrast, dithiothreitol reversed the effect of SNP on S-nitrosylation of JNK3. Furthermore, the inhibitor of nNOS (7-NI) and the inhibitor of iNOS (AMT) can decrease JNK3 phosphorylation through decreasing S-nitrosylation of JNK3. Our data suggest that endogenous NO synthesized by NO synthases can increase JNK3 phosphorylation by means of S-nitrosylation during global ischemia/reperfusion in rat hippocampus. However, the exogenous NO (SNP) can reverse the effect of endogenous NO by inhibiting S-nitrosylation of JNK3. Together, these results suggest that the exogenous NO may provide a new clue for stroke therapy.  相似文献   

16.
The NADPH-diaphorase (NADPH-d) histochemical technique is commonly used to localize the nitric oxide (NO) produced by the enzyme nitric oxide synthase (NOS) in neural tissue. The expression of inducible nitric oxide synthase (iNOS) is induced in the late stage of cerebral ischemia, and NO produced by iNOS contributes to the delay in recovery from brain neuronal damage. The present study was performed to investigate whether the increase in nitric oxide production via inducible nitric oxide synthase was suppressed by the administration of aminoguanidine, a selective iNOS inhibitor, as it follows a decrease of NADPH-diaphorase activity (a marker for NOS) after four-vessel occlusion used as an ischemic model. The administration of aminoguanidine (100 mg/kg i.p., twice per day up to 3 days immediately after the ischemic insult) reduced the number of NADPH-diaphorase positive cells to control levels. Our results indicated that aminoguanidine suppressed NADPH-diaphorase activity, and also decreased the number of NADPH-diaphorase positive cells in the CA1 region of the hippocampus following ischemic brain injury.  相似文献   

17.
Previous studies have demonstrated that the c-Jun N-terminal kinase (JNK) pathway plays an important role in inducing neuronal apoptosis following cerebral ischemic injury. JNK signaling pathway in activated during cerebral ischemic injury. It participates in ischemia-induced neuronal apoptosis. However, whether JNK signaling is involved in the process of neuronal apoptosis of diabetes-induced cerebral ischemia is largely unknown. This study was undertaken to evaluate the influence of cerebral ischemia–reperfusion injury on phosphorylation of JNK in diabetic rats. Twenty-four adult streptozotocin induced diabetic and 24 adult non-diabetic rats were randomly subjected to 15 min of forebrain ischemia followed by reperfusion for 0, 1, 3, and 6 h. Sixteen sham-operated diabetic and non-diabetic rats were used as controls. Apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL). Protein expression of phospho-JNK was examined by immunohistochemistry and Western blot. The numbers of TUNEL-positive cells and phospho-JNK protein expression in the cerebral cortices after 1, 3 and 6 h reperfusion was significantly higher in diabetic rats compared to non-diabetic animals subjected to ischemia and reperfusion (p < 0.05). Western blot analysis showed significantly higher phospho-JNK protein expression in the cerebral cortices of the diabetic rats after 1 and 3 h reperfusion than that was presented in non-diabetic animals subjected to ischemia and reperfusion (p < 0.05). These findings suggest that increased phosphorylation of JNK may be associated with diabetes-enhanced ischemic brain damage.  相似文献   

18.
目的通过观察选择性细胞周期抑制剂olomoucine对局灶性脑缺血边缘区神经元凋亡的影响,以探讨细胞周期调控与神经元细胞凋亡的关系。方法建立光化学法诱导大鼠局灶性脑缺血模型,随机分为脑缺血组(对照组和干预组)和假手术组,采用HE染色显示梗死灶并测定其面积;应用免疫荧光化学法检测梗死灶周围神经元核心抗原(NeuN)的表达及通过TUNEL方法检测神经元凋亡;免疫印迹(Western blot)观察损伤侧皮层NeuN、周期素蛋白A(cyclin A)和周期素蛋白B1(cyclin B1)蛋白的表达。结果缺血后3d对照组梗死灶面积占脑片面积百分比值的平均值明显大于干预组(P<0.05);缺血后缺血边缘区NeuN表达减弱,对照组NeuN表达明显弱于干预组(P<0.05);缺血后梗死灶周围可见大量TUNEL阳性染色细胞,而且对照组数量明显多于干预组(P<0.05);干预组大鼠NeuN(TUNAL双标阳性表达明显弱于对照组大鼠(P<0.05);NeuN的蛋白量的表达,干预组较对照组明显增加(P<0.05),而对照组cyclin A和cyclin B1蛋白量的表达明显高于干预组(P<0.05)。结论通过对细胞周期的调控,可减少神经元凋亡和脑梗死体积,从而为缺血性脑损伤后的神经元提供一个保护作用。  相似文献   

19.
We previously reported that inhibition of Rho-kinase (ROCK) by hydroxyl fasudil improves cognitive deficit and neuronal damage in rats with chronic cerebral ischemia (Huang et al., Cell Mol Neurobiol 28:757–768, 2008). In this study, fasudil mesylate (FM) was investigated for its neuroprotective potential in rats with ischemia following middle cerebral artery occlusion (MCAO) and reperfusion. The effect of fasudil mesylate was also studied in rat brain cortical and hippocampal slices treated with oxygen-glucose deprivation (OGD) injury. Gross anatomy showed that cerebral infarct size, measured with 2,3,5-triphenyltetrazolium chloride (TTC) staining, was significantly smaller in the FM-treated than in the non-FM-treated ischemic rats. In the brain regions vulnerable to ischemia of ischemic rats, fasudil mesylate was also found to significantly restore the enzyme protein expression level of endothelial nitric oxide synthase (eNOS), which was decreased in ischemia. However, it remarkably reduced the protein synthesis of inducible nitric oxide synthase (iNOS) that was induced by ischemia and reperfusion. In rat brain slices treated with OGD injury, fasudil mesylate increased the neuronal cell viability by 40% for cortex and by 61% for hippocampus, respectively. Finally, in the presence of OGD and fasudil mesylate, superoxide dismutase (SOD) activity was increased by 50% for cortex and by 58% for hippocampus, compared to OGD only group. In conclusion, our in vivo study showed that fasudil mesylate not only decreased neurological deficit but also reduced cerebral infarct size, possibly and at least partially by augmenting eNOS protein expression and inhibiting iNOS protein expression after ischemia-reperfusion. Xian-Ju Huang contributed equally to this article.  相似文献   

20.
ABSTRACT

Heart attack and oxygen deficiency may cause necrosis in the brain and other tissues. We investigated the histopathological effects of nitric oxide (NO) on ischemia/reperfusion in lung and hippocampus using a rat brain bilateral occlusion ischemia model. Male rats were assigned to sham (SH), ischemic preconditioning (PC), global ischemia (GI) and ischemic reperfusion (IR) groups. Before ischemia was induced, blood was drawn to induce hypovolemic hypotension and for blood gas testing. After sacrifice, samples of hippocampus were harvested. Sections were examined using hematoxylin and eosin (H & E) staining and immunostaining using primary antibodies for GFAP, S100β, iNOS, eNOS and the TUNEL method. Following ischemia, we found evidence of gliosis induced oxidative stress and apoptosis in the hippocampus. No significant differences were detected between the SH and PC groups. In the GI and IR groups, apoptosis and necrosis were observed in the hippocampus. Lung sections were stained with H & E and Masson’s trichrome (MT) and immunostained for iNOS and eNOS. The TUNEL method was used to detect apoptosis. Interstitial edema, vascular congestion, intra-alveolar hemorrhage, perivascular edema, neutrophil infiltration and disruption of alveoli were observed after global ischemia and ischemic reperfusion. Inflammatory cells were detected in the connective tissue. The IR and GI groups exhibited significantly more apoptotic cells than the SH or PC groups. Free radicals, such as nitric oxide (NO), that appear following ischemia and reperfusion in the brain may also injure the lungs. Increased NO in both lung and brain tissue suggests that apoptosis in these organs can be induced by reactive nitrogen species.  相似文献   

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