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1.
背景:右美托咪啶是一种高效、高选择性的α2肾上腺素受体激动剂,具有镇静、镇痛、抗焦虑等作用,对呼吸影响小。目的:观察鞘内注射右美托咪定对坐骨神经分支选择性损伤模型大鼠的镇痛作用。方法:雄性SD大鼠60只,随机均分为3组。除正常对照组外,另2组大鼠建立坐骨神经分支选择性损伤模型,右美托咪定组在造模后14 d内每天鞘内注射右美托咪定3 μg/kg,生理盐水组在同时注射等容量的生理盐水。于坐骨神经分支选择性损伤模型前、术后鞘内给药前和鞘内给药后2,7,14 d测定大鼠热刺激缩足反射潜伏期和机械刺激缩足反射痛阈值,并在术后第2,7,14天鞘内注射药物后,每组每个时间点分别处死4只大鼠,取其L4-6脊髓,RT-PCR及Western blot法分别检测脊髓背角蛋白激酶C mRNA及蛋白水平的表达情况,苏木精-伊红染色检测脊髓背角神经元形态学变化,免疫组织化学法检测脊髓背角蛋白激酶C蛋白表达的水平及分布情况。结果与结论:与正常对照组比较,给药前、给药后各时点生理盐水组和右美托咪定组热刺激缩足反射潜伏期和机械刺激缩足反射痛阈值均明显降低(P < 0.05);与生理盐水组比较,给药后各时点右美托咪定组热刺激缩足反射潜伏期延长和机械刺激缩足反射痛阈值均明显升高(P < 0.05);右美托咪定组脊髓背角蛋白激酶C表达明显明显低于生理盐水组,且在给药14 d时达到最低接近于正常对照组。右美托咪定组脊髓背角神经元凋亡程度也较生理盐水组轻微,在给药14 d时神经元形态基本接近正常对照组。提示鞘内注射右美托咪定可减轻坐骨神经分支选择性损伤模型引起的痛敏,可能与其抑制脊髓背角蛋白激酶C的表达相关。
中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程全文链接: 相似文献
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Alcohol neuropathy has been thought to involve decreased nerve function following chronic ethanol consumption. However, there is no reliably successful therapy, largely due to a lack of understanding of the central underlying mechanisms. The aim of this study was to investigate the mechanisms that contribute to the neuropathic pain-like state induced by chronic ethanol treatment in rats. Rats were chronically treated with ethanol diet (1.25-5% of ethanol) for over 70 days. Mechanical hyperalgesia was observed during ethanol consumption and even after ethanol withdrawal. Under these conditions, an immunohistochemical study showed an increase in metabotropic glutamate receptor 5 (mGluR5) immunoreactivity in the superficial spinal dorsal horn of chronic ethanol-fed rats. Furthermore, immunoblot analysis revealed that the protein level of mGluR5 was clearly increased following chronic ethanol consumption. These findings support the idea that the increased levels of mGluR5 in the spinal cord may be, at least in part, involved in the induction of ethanol-dependent neuropathic pain-like state. 相似文献
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突触后密度蛋白-95在大鼠脊髓发育过程中的表达变化 总被引:2,自引:0,他引:2
目的:探讨突触后密度蛋白-95(PSD-95)在大鼠脊髓发育过程中的表达变化以及细胞定位。方法:采用实时定量PCR(Real-Time PCR)和Western blot测定发育不同时期PSD-95 mRNA及蛋白水平的表达变化。采用免疫荧光染色显示PSD-95在发育脊髓中的细胞定位。结果:大鼠脊髓发育过程中PSD-95 mRNA及其蛋白水平从生后1d开始逐渐升高,在生后1周达高锋,成年后维持在一定的生理水平。免疫荧光双标证实PSD-95在生后发育早期主要定位于脊髓灰质,与神经元的标记物NeuN和突触的标记物synapsin存在共定位;成年后广泛分布于脊髓前角、后角以及白质,分别与NeuN和synapsin以及小胶质细胞的标记物OX-42共定位。结论:大鼠脊髓发育过程中PSD-95在基因和蛋白水平呈现明显的时相变化,在生后发育早期主要表达在前角运动神经元和后角感觉神经元,提示PSD-95参与了神经元的发育和成熟。 相似文献
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We have characterized segmental and laminar distribution patterns of Fos-immunopositive (Fos-IP) neurons in spinal cord segments L3-L6 after carrageenan treatment. A large number of Fos-IP neurons was found in the medial region of the ipsilateral dorsal horn laminae I-II at 4 and 6 h postinjection (pi). At one day pi, the number of Fos-IP neurons was decreased significantly, which correlated with suppression of inflammation in the affected hind paw. Bilaterally, Fos-IP neurons reappeared in the L3-L6 spinal cord segments at 3-4 days pi, mainly in the deep laminae LV-LVI. However, signs of inflammation had distinctly attenuated. Our data indicate a biphasic trend in Fos-IP in this experimental model of inflammation. 相似文献
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大鼠脊髓慢性压迫性损伤实验模型的建立 总被引:13,自引:0,他引:13
目的:建立一种新型大鼠脊髓慢性压迫实验动物模型,为探索脊髓受压后的病理生理机制奠定基础。方法:根据大鼠脊柱解剖结构特点自行设计一种大鼠脊髓压迫器,用以制作大鼠慢性压迫模型。运用行为学、影像学、TTC、HE、Tunnel等方法,了解动物行为学变化及受压节段脊髓病理学改变,以评价模型的可靠性。结果:脊髓压迫后渐次出现肌力减退、行动瘫痪;TTC结果显示,在各时段可见脊髓缺血范围与压迫时间及压迫强度相关;压迫后,脊髓出现组织水肿、神经元空泡化、白质疏网状改变及退行性变,以及神经元和胶质细胞的凋亡。结论:(1)用大鼠脊髓压迫器制作的大鼠脊髓慢性压迫缺血性损伤模型,具有方法简单、科学、重复性强等特点;(2)脊髓压迫程度可根据实验目的不同进行调节;(3)本实验为脊髓压迫性损伤机制的研究提供了一种理想的动物试验模型。 相似文献
6.
Brandenburger T Castoldi M Brendel M Grievink H Schlösser L Werdehausen R Bauer I Hermanns H 《Neuroscience letters》2012,506(2):281-286
Neuropathic pain is accompanied by significant alterations of gene expression patterns in the somatosensory nervous system. The spinal cord is particularly prone to neuroplastic changes. Since the expression of microRNAs (miRNAs) has been linked to numerous pathophysiological processes, a contribution of miRNAs to the maladaptive plasticity of the spinal cord in neuropathic pain is possible. Aim of the present study therefore was to characterize the specific expression pattern of miRNAs in the rat spinal cord. Furthermore, we evaluated the time-dependent changes in expression patterns of spinal miRNAs in the chronic constriction injury (CCI) model of neuropathic pain in rats. Results from miRNA microarrays revealed a distinct expression pattern of miRNAs in the rat spinal cord. MiRNAs-494, -720, -690 and -668 showed the highest signal intensities. Members of the let-7 family as well as miR-124 belong to the group of the most highly expressed miRNAs. Induction of neuropathic pain by CCI did not lead to relevant differences in spinal miRNA expression levels compared to sham-operated animals at any studied time point. Therefore, modulation of miRNAs does not seem to contribute significantly to the changes in gene expression that cause neural plasticity in the spinal cord in this model of chronic neuropathic pain. 相似文献
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目的:研究N-甲基-D-天冬氨酸(NMDA)受体2B型受体(NR2B)参与脊髓损伤后慢性神经病理性痛的机制。方法:制作脊髓半横断大鼠模型,von Frey纤维丝测量机械性刺激缩足阈值变化,Western Blot观察脊髓背角NR2B表达时程变化;同时采用行为药理学方法,鞘内给予NR2B特异性拮抗剂ifenprodil,观察对机械性刺激缩足阈值及NR2B表达的影响。结果:脊髓半横断术后大鼠双侧后足出现触诱发痛状态,NR2B在腰段脊髓双侧背角表达上调。鞘内给予ifenprodil逆转了大鼠的痛敏状态,伴随着NR2B在脊髓背角表达下调。结论:NR2B可能参与脊髓损伤后慢性神经病理性痛的发生发展,特异性拮抗NR2B可能是临床治疗脊髓损伤致慢性神经病理性痛的潜在策略。 相似文献
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Huai Huang Lei Xue Xu Zhang Qibiao Weng Huiqiang Chen Jing Gu Shuilin Ye Xiaodong Chen Wei Zhang Huangyi Liao 《International journal of clinical and experimental pathology》2013,6(7):1337-1342
Objective: To investigate the effect of hyperbaric oxygen therapy (HBOT) on the iNOS mRNA-iNOS-NO signaling pathway and neurofunction protected in a rat spinal cord injury model. Methods: A total of 36 Sprague-Dawley rats were randomly divided into 3 groups: control group (n=12), SCI group (n=12) and SCI + HBOT group (n=12). SCI + HBOT group In the SCI group and SCI + HBOT groups, SCI was performed on rats. In the SCI + HBOT group, rats with SCI underwent HBO treatment 30 min after SCI for 24 sessions. After HBO therapy, measurement of motor evoked potential (MEP), Basso, Beattie, Bresnahan (BBB) scoring and pathological examination were done. RT-PCR and immunohistochemistry were employed to detect the mRNA and protein expression of iNOS, respectively. Diazo colorimetry was performed to detect the serum NO content. Results: The mRNA and protein expression of iNOS in the spinal cord and the serum NO content were markedly increased in the SCI group as compared to the control group (P<0.05). However, the mRNA and protein expression of iNOS and the serum NO content were dramatically reduced in the SCI + HBOT group as compared to the SCI group (P<0.05). Conclusion: HBO therapy can promote the neuroprotection following SCI, which may be related to the effect of HBO on the iNOS mRNA-iNOS-NO signaling pathway. 相似文献
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大鼠脊髓全横断后神经营养素-3在红核表达的变化 总被引:1,自引:0,他引:1
目的:研究大鼠脊髓全横断后神经营养素-3(NT-3)在红核表达的变化,为进一步探索脊髓损伤后的再生修复机制和神经营养因子治疗脊髓损伤提供实验依据。方法:雄性SD大鼠36只随机分为3组,脊髓横断组:大鼠脊髓在胸10~11节段之间完全横断,按存活时间不同又分为术后1、3、7及14d组;假手术组(只行椎板切除术);正常对照组。动物到达存活时间点后,应用免疫组织化学ABC法和图像分析技术检测NT-3在红核的表达。结果:对照组和实验组红核有NT-3阳性细胞。脊髓全横断后红核NT-3的表达逐渐增高,于术后7d达高峰,后缓慢下降。结论:脊髓全横断后红核对NT-3的表达增加,内源性NT-3的增加可能有利于受损的红核内神经元的存活与再生。 相似文献
10.
We have shown previously that mats made from the glycoprotein fibronectin are permissive for axonal growth when implanted into the injured spinal cord. Recent evidence has indicated that fibronectin and its peptides also have neuroprotective effects in the CNS. We have therefore examined the neuroprotective effects of fibronectin applied to a spinal cord injury site. Adult rats with fibronectin mats implanted into a spinal cord lesion cavity had decreased apoptosis in the intact adjoining spinal cord tissue at 1 and 3 days post-injury compared to rats that had gelfoam implanted into the lesion cavity. Rats with fibronectin mat implants also showed enhanced hindlimb locomotor performance for the first 3 weeks post-surgery compared to control animals. To further examine the neuroprotective potential of fibronectin following spinal cord injury, we examined the effects of placing fibronectin mats over the site of a spinal cord hemisection or of delivering a solution derived from a dissolved fibronectin mat. The effects of these treatments were compared with control animals and animals that were treated with a fibronectin peptide (PRARIY) that has been shown to decrease secondary damage in a rodent model of cerebral ischemia. Results showed that both types of fibronectin mat treatment resulted in decreased lesion size, apoptosis, and axonal damage within the first week post-injury compared to control animals and were comparable in their neuroprotective efficacy to treatment with the fibronectin peptide. The results of the current study indicate that fibronectin based biomaterials have neuroprotective effects following spinal cord injury, in addition to their previously reported ability to promote axonal regeneration. 相似文献
11.
目的:探讨利用自体周围神经组织移植修复大鼠陈旧性脊髓损伤病理机制,为临床应用提供实验依据。方法:利用改良Allens撞击方法建立脊髓打击损伤模型,12周后,将大鼠分为2组,实验组切取后肢腓肠神经,利用显微外科技术去除神经外膜,将其修剪成小段,游离移植于脊髓损伤处,对照组不作处理。分别于术后2、4、12周,在光镜及电镜下观察脊髓损伤段及移植周围神经再生情况。术后4、8及12周分别对两组动物进行脊髓诱发电位检查。结果:对照组脊髓变性,可见瘢痕和空洞,实验组术后12周,损伤区脊髓与周围神经融合良好。脊髓诱发电位检查神经移植组优于对照组。结论:周围神经组织游离移植修复大鼠陈旧性脊髓损伤后,存活良好,为再生轴突跨越损伤段脊髓提供通道。 相似文献
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The aim of the present work was to study pathomorphological and functional changes after induced focal photothrombosis of blood vessels in the thoracic part of the spinal cord in rats. Neuron abnormalities characteristic of ischemia were seen at the focus of experimental photothrombosis and in the transitional zone, along with symptoms of impaired motor and pelvic organ function. The focal photothrombosis method can be used to model spinal cord ischemia for the development of pharmacological correction methods and the recovery of impaired sensorimotor functions. Translated from Morfologiya, Vol. 133, No. 1, pp. 35–38, January–February, 2008. 相似文献
14.
目的:研究锌对神经病理性疼痛(NPP)模型小鼠脊髓后角磷酸化(p)的细胞外信号调节激酶(ERK)表达的影响.方法:C57/BL6小鼠随机分4组,对照组正常喂养2周后足底注射生理盐水;正常喂养2周后足底注射辣椒素;低锌喂养(锌0.85 mg/kg)2周后足底注射辣椒素;高锌喂养(227mg/L)2周后足底注射辣椒素.应用原子吸收光谱、热痛阈检测、免疫组织化学和图像分析技术检测注射后7d锌对动物行为学以及脊髓后角pERK表达的影响.结果:对照组小鼠血清和脊髓中含有丰富的锌离子,脊髓后角有少量pERK表达;当足底注射辣椒素致痛后,血清和脊髓中的锌减少,热痛敏增加,脊髓后角pERK表达增多;低锌喂养能加重缺锌和热痛敏,脊髓后角pERK表达更多;高锌喂养能使血清和脊髓锌增多,降低热痛敏和脊髓后角pERK表达.结论:锌能抑制NPP模型小鼠热痛敏和脊髓后角pERK的表达,锌可能参与了神经病理性疼痛的形成与维持. 相似文献
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Kiyomitsu Oyanagi Yasuji Yoshida Fusahiro Ikuta 《Virchows Archiv : an international journal of pathology》1988,412(3):215-224
Summary We examined the histological findings and cytoarchitectonic alterations in the rat spinal cord following matrix cell degeneration caused at different developmental stages, from neural plate formation through neuroblast generation. Ethylnitrosourea (ENU) 20 mg/kg body weight was administered transplacentally to the fetuses on the 10th embryonic day (E10) to 14th. The observations were made until the 21st postnatal day. Normally, mitoses were present scatteredly in the matrix cell layer of the neural plate or neural tube on El0 or E11, and gradually restricted to the dorsal portion of the alar plate as development occurred. The localization and number of degenerative cells as well as the site and degree of neuronal decrease in the completed dysgenetic spinal cord seemed to correlate with the topography and frequency of the mitoses in the matrix cell layer at the time of ENU administration. Disorder in the pattern of cytoarchitecture of neurons was not observed. The degree of hypoplasia of the white matter was proportional to the intensity of decrease of the spinal neurons. Aberrant myelinated fibers were not seen. No reactive gliosis, fibrosis or abnormal vascularization was observed at any time.This study was supported by a Grant-in-Aid for Scientific Research (A) No. 60440046 from the Ministry of Education, Science and Culture, Japan 相似文献
18.
Implication of spinal protein kinase C in the suppression of morphine-induced rewarding effect under a neuropathic pain-like state in mice 总被引:2,自引:0,他引:2
Narita M Oe K Kato H Shibasaki M Narita M Yajima Y Yamazaki M Suzuki T 《Neuroscience》2004,125(3):545-551
We previously demonstrated that spinal protein kinase C (PKC) is involved in the development of a neuropathic pain-like state induced by sciatic nerve ligation, and the morphine-induced rewarding effect is attenuated by sciatic nerve ligation in rodents. Here we first investigated whether sciatic nerve injury could change the activity of a conventional PKC (cPKC) and an atypical PKC isoform PKCzeta in the mouse spinal cord. The second experiment was to investigate whether direct inhibition of spinal PKC by intrathecal (i.t.) administration of a specific PKC inhibitor, 2-[8-[(dimethylamino)methyl]-6,7,8,9-tetrahydropyrido[1,2-a]indol-3-yl]-3-(1-methyl-1H-indole-3-yl)maleimide (RO-32-0432), could affect the rewarding effect induced by morphine following sciatic nerve ligation in mice. We found here that the activities of both cPKC and PKCzeta in the spinal cord were clearly increased following sciatic nerve ligation. Furthermore, i.t. administration of RO-32-0432 reversed a long-lasting pain-like syndrome as indicated by thermal hyperalgesia following sciatic nerve ligation in mice. These data provide direct evidence that activated cPKC and PKCzeta in the spinal cord may contribute to the development and maintenance of neuropathic pain. In the present study, we confirmed that the morphine-induced place preference was significantly suppressed by sciatic nerve ligation. It should be mentioned that i.t. pretreatment with RO-32-0432 significantly reversed the attenuation of morphine-induced rewarding effect following sciatic nerve ligation. These results suggest that activation of PKCs, including cPKC and PKCzeta, within the spinal cord is directly responsible for the attenuation of the morphine-induced rewarding effect under a neuropathic pain-like state following sciatic nerve ligation in mice. 相似文献
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目的观察大鼠脊髓全横断(SCT)后横断端细胞凋亡及caspase-3 mRNA、蛋白的表达变化并探讨其意义。方法SD大鼠90只,手术组(SCT组)动物选择在T10节段全横断脊髓,假手术组除不横断外其余步骤相同。TUNEL法检测脊髓横断端凋亡情况,免疫组织化学、RT-PCR、Western blot技术检测不同时间点caspase-3 mRNA、蛋白表达变化。结果SCT后横断端脊髓灰质白质均检测到凋亡细胞,caspase-3在损伤周围组织呈阳性,RT-PCR、Western blot显示1d组基因及蛋白均明显上调,3d、7d、14d、21d组mRNA逐渐下降,且3d组依然高于假手术组;3d、7d、14d组蛋白逐渐下降而21d组又略有回升,且3d、21d组依然高于假手术组。结论SCT后凋亡主要在早期出现,随时间进展呈逐渐下降趋势。 相似文献