滥用氯胺酮引起膀胱功能障碍患者膀胱组织中P2X1受体的表达及其意义

目的 研究P2X1受体在滥用氯胺酮导致膀胱功能障碍患者膀胱组织中的表达及其临床意义.讨论P2X1受体在滥用氯胺酮引起膀胱功能障碍中的作用.方法 采用免疫组织化学方法分别检测36例滥用氯胺酮引起膀胱功能障碍患者(实验组)和36例正常膀胱组织(对照组)中P2X1受体、M2受体、M3受体的表达情况,利用全自动显微镜及图像分析系统对免疫组化染色结果进行图像采集分析、测量其平均灰度值,同时比较两组间P2X1受体、M2受体、M3受体表达的差异.结果 P2X1受体主要在膀胱黏膜移行上皮细胞表达,实验组P2X1受体表达明显增强,与对照组比较差异有统计学意义(P＜0.01),而M2受体、M3受体表达与对照组比较无明显差异(P＞0.01).结论 滥用氯胺酮引起膀胱功能障碍患者膀胱组织中P2X1受体表达显著增强,而M2受体、M3受体并未异常表达,提示P2X1受体上调可能在滥用氯胺酮导致膀胱过度活动中发挥关键作用.     

女性膀胱过度活动症患者膀胱内P2X3受体的表达及其意义

目的:研究P2X3受体在女性膀胱过度活动症患者膀胱内的表达及其临床意义,讨论P2X3受体在膀胱过度活动症中的作用。方法:采用免疫组织化学SABC法分别检测21例女性膀胱过度活动症患者和9例正常膀胱组织中P2X3受体的表达情况,利用全自动显微镜及图像分析系统对免疫组化染色结果进行图像采集分析,测量其平均光密度值,同时比较两组间P2X3受体表达的差异。结果:P2X3受体表达主要位于膀胱黏膜及黏膜下层,实验组P2X3受体表达显著增强,平均光密度值为(0.491 20±0.038 48),正常组P2X3受体表达明显偏低,平均光密度值为(0.260 70±0.031 43),组间比较差异有统计学意义(P<0.05)。结论:女性膀胱过度活动症患者膀胱组织中P2X3受体的表达显著提高,提示P2X3受体与女性膀胱过度活动症的发病机制密切相关,膀胱感觉功能异常可能是导致女性膀胱过度活动症发生的主要病因之一。     

P2X受体与膀胱过度活动症

随着不稳定膀胱中阿托品抵抗性逼尿肌收缩的深入研究,学者们发现膀胱逼尿肌收缩和膀胱充盈两方面功能除了接受M受体支配外,嘌呤受体（P2X受体）传导途径也参与逼尿肌感觉和运动功能的调节。病理条件下,P2X受体传导途径在泌尿系统病理生理中的作用越来越明显,P2X受体与膀胱过度活动症之间的关系越来越受到重视。本文就膀胱过度活动症时P2X各亚型在逼尿肌上的表达异常和功能异常与膀胱过度活动症之间可能存在的联系作一综述。     

P2X受体与膀胱过度活动症

随着不稳定膀胱中阿托品抵抗性逼尿肌收缩的深入研究,学者们发现膀胱逼尿肌收缩和膀胱充盈两方面功能除了接受M受体支配外,还接受其他途径的支配。病理条件下,嘌呤受体（P2X受体）途径也参与逼尿肌感觉和运动功能的调节,P2X受体传导途径在泌尿系统病理生理中的作用越来越明显,P2X受体与膀胱过度活动症之间的关系越来越受到重视。本文就膀胱过度活动症时P2X各亚型在逼尿肌上的表达异常和功能异常与膀胱过度活动症之间可能的联系作综述。     

P2X嘌呤受体在肠神经系统中的表达及功能

P2X受体为配体门控离子通道,细胞外ATP是其天然配体.当任何一种亚型的P2X受体与细胞外ATP结合时,P2X通道打开,允许阳离子(钙、钠、钾离子等)通过.肠神经系统(ENS)由肠道肌间神经丛和黏膜下神经丛组成,二者都存在P2X受体,它们在生理和病理情况下介导不同的效应.本文主要就肠神经系统内P2X受体的分布以及相关功...     

结肠癌中P2X7 受体表达水平及其与患者预后的关系

目的:探讨结肠癌组织中P2X 亚单位受体(P2X7)表达与结肠癌肿瘤特征及患者预后的关系。方法:选取2017 年1 月—2018 年1 月在河北中石油中心医院手术治疗的120 例结肠癌患者,获取其结肠癌组织及癌旁组织标本,采用免疫组化染色检测P2X7 受体的阳性表达率,分析不同预后患者的病理学特征差异,同时分析P2X7 受体与患者3 年预后结局的关系。结果:结肠癌组织中,P2X7 受体低表达率为65.0%,高于癌旁组织的28.3%,差异有统计学意义(P <0.05);随访3 年,P2X7 受体低表达组患者的死亡率为52.6%,高于高表达组的33.3%,差异有统计学意义(P <0.05);生存分析结果显示,P2X7 受体低表达组患者的生存时间短于高表达组患者,差异有统计学意义(Log Rank χ2=4.652,P =0.031);Logistic 回归分析结果显示:TNM 分期高、切缘阳性、淋巴结转移阳性、脉管浸润、P2X7 受体低表达是结肠癌患者不良预后的独立危险因素(P <0.05)。结论:结肠癌组织中的P2X7 受体呈低表达,并且是结肠癌患者预后不良的独立危险因素。     

P2X受体在膀胱中的研究进展

P2X受体是细胞外非选择性门控阳离子通道,细胞外ATP是其天然配体,目前研究发现P2X受体有7个亚型,即P2X1-P2X7,它们在膀胱上的表达和分布各不相同,与膀胱的收缩功能关系密切,当膀胱发生病理改变时,它们在膀胱上的表达和功能也会发生改变.特别是P2X1,P2X3受体亚型目前的研究提示它们可能是起作用的主要受体亚型.本文对这方面的研究进展作一综述.     

隔姜灸对大鼠脊髓损伤后神经源性膀胱M2、M3乙酰胆碱mRNA及P2X3受体表达的影响

目的 探讨隔姜灸改善脊髓损伤大鼠神经源性膀胱症状的作用靶点,为脊髓损伤神经源性膀胱患者临床干预提供理论基础。 方法 选取SD大鼠为实验动物,随机分组后,按照改良Allen′s法建立T10脊髓损伤模型,根据评估标准,筛选符合脊髓损伤后神经源性膀胱标准的动物模型纳入模型组和隔姜灸组;假手术组仅切除T10椎板,不破坏脊髓;各组均纳入10只SD大鼠。三组术后均给予抗感染、创口护理及Crede手法辅助排尿。隔姜灸组同时行隔姜灸治疗,即术后第1天开始,每日1次,每次每个穴位灸10 min,连续12 d。 结果 隔姜灸组治疗后嘌呤能P2X3受体的相对表达水平及M2、M3乙酰胆碱mRNA的相对表达水平显著高于模型组（均P＜0.05）。 结论 隔姜灸治疗可提高脊髓损伤大鼠脊髓神经节嘌呤能P2X3受体及膀胱组织中M2、M3乙酰胆碱mRNA的表达水平,从而有利于改善神经源性膀胱功能障碍。     

P2X嘌呤受体与痛觉调制

嘌呤受体可分为P1和P2受体,在后者的诸亚型中仅P2X受体属配体门控离子通道受体,P2Y受体及其他亚型均为G蛋白耦联受体。P2X受体与伤害性感受器的分布相一致,并参与不同疼痛的调制。现就P2X受体以及其在不同疼痛状态中的作用作一简要综述。     

P2X嘌呤受体与痛觉调制

嘌呤受体可分为P1和P2受体,在后者的诸亚型中仅P2X受体属配体门控离子通道受体,P2Y受体及其他亚型均为G蛋白耦联受体。P2X受体与伤害性感受器的分布相一致,并参与不同疼痛的调制。现就P2X受体以及其在不同疼痛状态中的作用作一简要综述。     

Effects of intracavernous injection of P2X3 and NK1 receptor antagonists on erectile dysfunction induced by spinal cord transection in rats

This study aimed to explore the effects of intracavernous injection (ICI) of P2X3 and NK1 receptor antagonists on erectile dysfunction (ED) induced by spinal cord transection in rats. Sixty male Sprague–Dawley (SD) rats were randomly divided into the following three groups (20 rats each group): sham operation group (C group), thoracic spinal cord transection group (T group) and sacral spinal cord transection group (S group). An ED model was established through complete transection of the thoracic or sacral spinal cord. Intracavernous pressure (ICP) with and without injection of P2X3 (Suramin) or NK1 (GR82334) receptor antagonists was recorded 3 weeks after surgery. Immunohistochemistry was employed to detect the expression of P2X3 and NK1 receptors in the dorsal root ganglion (DRG) and smooth muscle of corpus cavernosum. Data were processed with SPSS 17.0. ICI with Suramin (0.1, 0.3 and 1 mm ) or GR82334 (0.1, 0.3 and 1 mm ) increased ICP dose dependently in the T and S groups. The expression of P2X3 and NK1 receptors in DRG and smooth muscle of corpus cavernosum was up‐regulated in the T and S groups. It is concluded that ICI of P2X3 and NK1 receptor antagonists may improve the recovery of erectile function in a rat model with ED after spinal cord transection.     

Expression of P2X3 purinoceptors in suburothelial myofibroblasts of the normal human urinary bladder

Objectives:   To investigate the possible localization of P2X3 receptors on suburothelial myofibroblasts and the structural relationship between these cells and sensory nerves in the human bladder.
Methods:   Bladder specimens were obtained from 17 patients. Cryosections were prepared for immunofluorescent investigations using various antibodies, including cytoskeletal marker vimentin, α-smooth muscle actin (α-SM actin), desmin, P2X3 purinoceptors, afferent nerve fibers marker calcitonin gene related peptide, substance P and Griffonia simplicifolia isolectin B4. Double-labeling was employed to determine the spatial relationship of myofibroblasts with P2X3 purinoceptors and afferent fibers.
Results:   In the bladder suburothelium, there was a network of fusiform vimentin-positive cells with branching processes. Almost all of these vimentin-positive myofibroblasts showed immunoreactivity for α-SM actin. P2X3 receptors' immunoreactivity was not distributed on any of the suburothelial afferent nerve fibers including calcitonin gene related peptide, substance P and isolectin B4-containing nerves in the bladder. However, abundant P2X3 receptors localized on the small soma and branching processes of suburothelial myofibroblasts. Furthermore, a large number of suburothelial afferent fibers were found to contact closely with myofibroblasts, or intermingle with each other.
Conclusions:   In the suburothelium of the human bladder, there was a layer of vimentin-positive myofibroblasts. Almost all vimentin-positive myofibroblasts showed double labeling for α-SM actin. These cells expressed P2X3 receptors. Suburothelial myofibroblasts may be intermediate in processing adenosine triphosphate-mediated sensory activation.     

Effect of the neuropathic pain receptor P2X3 on bladder function induced by intraperitoneal injection of cyclophosphamide (CYP) in interstitial cystitis rats

BackgroundThe role of purinergic receptor P2X3 in pathological bladder dysfunction and chronic pelvic pain remains unclear. We aim to investigate the effect of P2X3 on bladder function in interstitial cystitis (IC) through the IC rat model induced by cyclophosphamide (CYP).MethodsA total of 120 female Sprague-Dawley (SD) rats were randomly divided into 6 groups: control, CYP-4h, CYP-48h, CYP-10d, CYP-30d, and CYP-45d groups. The control group was injected with normal saline. The rats in the CYP-4h and CYP-48h groups were given a single high dose. The rats in the CYP-10d, CYP-30d, and CYP-45d groups were given a low dose of CYP repeatedly every three days. Bladder voiding function was measured using urodynamic techniques to observe the effect of the P2X3 receptor on bladder function in CYP-induced IC.ResultsThe rats in the CYP-4h group showed significant overactivity of the bladder compared with the control group, the bladder voiding interval was shortened (P<0.01), and the maximal voiding pressure was increased (P<0.01). At the same time, the degree of overactive bladder in the CYP-48h, CYP-10d, CYP-30d, and CYP-45d groups became increasingly serious, the interval of bladder micturition was shortened stepwise (P<0.01), and the maximal micturition pressure was increased stepwise (P<0.01). Compared with the control group, the CYP-48h group mainly showed a shorter bladder voiding interval (P<0.01), lower voiding volume, and higher activation of mast cells and inflammatory factors in the bladder. In the CYP-10d group, bladder mast cell activation and inflammatory factors increased significantly. Intrathecal injection (IT) of A-317491 significantly prolonged the bladder voiding intervals in CYP-4h, CYP-48h, CYP-10d, CYP-30d, and CYP-45d rats (P<0.01), and the maximal voiding pressure of the CYP-4h, CYP-48h, CYP-10d, CYP-30d, and CYP-45d groups was significantly decreased (P<0.05), while the maximal voiding pressure of the CYP-10d group was not significantly affected.ConclusionsP2X3 receptors in dorsal root ganglion (DRG) play an important role in bladder function induced by intraperitoneal injection of CYP in rats. IT of P2X3 inhibitors can significantly improve the grade of bladder voiding dysfunction and chronic pelvic pain.     

P2X4受体与慢性疼痛

背景 慢性疼痛目前尚无有效安全的治疗方法,其机制越来越受到重视,近年来研究发现P2X4受体在疼痛信号转导中起着重要的作用. 目的 阐明P2X4受体在慢性疼痛发生发展过程中的作用及其机制. 内容 现就P2X4受体参与慢性疼痛如神经病理性痛、炎性痛和癌痛的作用及机制作一综述. 趋向 为靶向治疗慢性疼痛提供新的思路.     

Changes in intracellular calcium concentration and P2X1 receptor expression in hypertrophic rat urinary bladder smooth muscle

AIMS: Contractile responses to purinergic activation in the urinary bladder are altered in outflow obstruction (O). We determined if the lowered contractile response to adenosine triphosphate (ATP) in obstructed rat urinary bladder was due to changes in calcium handling or in P2X1 purinoceptor density. MATERIALS AND METHODS: O was created in rat by partial ligature of the urethra, with non-obstructed rats as controls (C). Force and intracellular calcium were measured in bladder strips activated with ATP. Tissue was sectioned for light and electron microscopy and analyzed with Western blot using a P2X1 antibody. RESULTS: Bladder weight increased from 66 +/- 3 (C) to 206 +/- 17 mg (O) (n = 6). ATP gave a transient contractile response which was decreased in the obstructed strips (C: 161 +/- 20; O: 63 +/- 16% of high-K+ force). Intracellular calcium concentration after ATP activation in the obstructed bladder muscle was about 50% of that in the control preparations (C: 669 +/- 110; O: 335 +/- 59 nM). Half-time for calcium influx was increased in the O group. P2X1 immunoreactivity per unit bladder weight was similar in the two groups. Cell membrane area per unit wet weight was decreased in the O group. CONCLUSIONS: Attenuated contractile responses to ATP in obstructed rat urinary bladder are due to a lowered rate of calcium influx and maximal peak calcium concentration. This change in Ca2+transients is not due to a decrease in P2X1 receptor density in the smooth muscle cell membranes. Possibly, the increase in cell volume buffers the rapid and transient influx of Ca2+ following purinoceptor activation in the obstructed bladder.     

环氧合酶-2在膀胱癌中的表达及临床意义

目的检测环氧合酶-2（cyclooxygenase-2,COX～2）在膀胱移行细胞癌组织中的表达及其意义。方法采用免疫组化法检测50例膀胱癌组织和10例正常组织中COX-2蛋白的表达,并结合临床资料进行分析。结果正常组织中COX-2蛋白的表达水平明显低于肿瘤组织（P〈0．001）。G1级和G2～G3级膀胱癌中COX-2蛋白表达的阳性率分别为20％、60％,差异有统计学意义（P=0．022）。非肌层浸润性膀胱癌和浸润性膀胱癌中COX-2蛋白表达的阳性率为36．8％和83．3％,差异有统计学意义（P=0．005）。COX-2表达与患者的年龄、性别、肿瘤的数目及大小无明显相关性（P〉0．05）。结论COX-2在高分级膀胱移行细胞癌和侵袭性膀胱移行细胞癌中阳性表达率显著上升,表明COX-2可能在膀胱移行细胞癌的形成中起重要作用,有望为膀胱癌的靶向治疗提供新的途径。