阿片类药物成瘾机制的研究进展

阿片（ｏｐｉｏｉｄ）包括天然的鸦片如吗啡,半合成的如海洛因,和全合成的如可待因、羟吗啡、美沙硐、二氢埃托啡、度冷丁、芬太尼,兼有激动剂和拮抗剂作用的镇痛新和丁丙诺啡由于产生类似于阿片激动剂的生理和行为效应也归类于阿片类。阿片类药物在临床上主要用于镇痛麻醉、止泻和镇咳。然而现在阿片类药物滥用已成为一个紧迫的社会问题,尤其是海洛因,在我国登记在册的海洛因成瘾者,１９９７年就已达５４万人之多。目前关于阿片成瘾的研究主要集中于躯体依赖和精神依赖机制。躯体依赖主要表现为耐受和戒断反应,而精神依赖主要表现为…     

内啡肽对体温的影响

早已知道,阿片类药物(如吗啡)具有影响体温的药理作用。自从1975年Hughes等发现两种脑啡肽(甲啡肽、亮啡肽),证实体内存在着内源性阿片样肽类物质(内啡肽)以来,人们对这类物质的广泛生理作用进行了大量研究。如阿片类药物一样,内啡肽也能影响动物的体温,近年来在这方面的研究取得了不少进展,现作简要介绍。     

阿片类物质诱导的痛觉过敏与趋化因子及其受体

阿片类物质(如吗啡)是当前缓解由创伤、手术,以及癌症引起的严重疼痛的首选药物.阿片类药物也越来越多的被应用于慢性以及非癌性的病理性疼痛的治疗.但是,长时间应用阿片类药物可引起诸如药物耐受等一系列严重的问题,患者需要使用更大剂量的药物才能达到相同的镇痛效果.     

阿片与阿片受体的研究

一、历史的回顾: 1. 阿片及阿片生物碱:阿片之被认识已有约两千年的历史。在十六世纪时即被广泛应用于镇痛、止泻、止咳、解除焦虑和催眠。由于疗效卓著,曾有“天赐良药”的美名。 1803年首先从阿片中提取得到阿片生物碱吗啡纯品,随后又发现和合成了一系列的衍生物(如可待因、罂粟碱、依托啡、杜冷丁等),但难以获得药效高又不成瘾的阿片类制剂。1915～1940年合成丙烯吗啡后,由于它本身具有镇痛作用又能部份拮抗吗啡的作用,被认为是一种部份激动剂(partial agonist),于1951年起被用于治疗吗啡中毒。     

吗啡对大鼠海马神经元钾、钙通道的作用

吗啡是常见的阿片类镇痛药,长时间应用可导致吗啡耐受和依赖,其作用机制十分复杂。海马中同时包含μ,κ,δ阿片受体,与吗啡耐受及依赖有一定的关系,并参与机体的痛觉调制过程,因而了解吗啡对海马神经元离子通道的作用对阐明吗啡的镇痛、耐受及依赖机制具有重要的理论及实际意义。本文报导吗啡对培养的海马神经元电压门控性钾、钙     

阿片类物质引起细胞内钙离子和环磷腺苷含量变化及其对心肌细胞功能的调节

本文观察了阿片类物质影响体外培养心肌细胞搏动功能的生化机制。发现阿片物质对心肌细胞的直接作用机制涉及胞内[Ca~(2+)]i浓度和腺苷酸环化酶(AC)活性改变的调节,方式较复杂。广谱型阿片受体激动剂(κ-δ-μ)依托啡促进外钙内流和内钙释放,增加心肌细胞内[Ca~(2+)]i,其他一些阿片物质则未发现此种作用,吗啡,甲硫脑啡肽对AC活性具有双相调节;强啡肽,β-内啡肽则表现为刺激AC活性。AC活性改变受G蛋白亚基Gi和Gs的共同调控,但以Gs为主。     

阿片类物质对淋巴细胞内环磷酸腺苷及游离钙的影响

文本观察了几种阿片类物质对小鼠脾脏淋巴细胞内环磷酸腺苷,游离钙及钙调蛋白的影响。结果表明:吗啡、α-CAO、MENK、DADLE及强啡肽均降低小鼠脾脏淋巴细胞内环磷酸腺苷水平,升高淋巴细胞内游离钙浓度,增加淋巴细胞内钙调蛋白活性。预先给予纳洛酮能够阻断阿片类物质的作用。说明阿片类物质的作用是通过阿片受体介导的。     

μ、κ、δ阿片受体及酪氨酸羟化酶在MN9D细胞中的表达

目的:检测多巴胺能性MN9D细胞中是否存在μ、κ、δ 3种阿片类受体及多巴胺能神经元特异性标记物酪氨酸羟化酶(TH)的表达,为建立吗啡依赖MN9D细胞模型奠定基础.方法:培养MN9D细胞后,采用免疫荧光标记观察μ、κ、δ3种受体蛋白表达状态;RT-PCR检测μ、κ、δ3种阿片类受体的mRNA表达;TH免疫荧光标记,观察多巴胺能神经元的表达数量.结果:免疫荧光及PCR结果均显示MN9D细胞中存在μ、κ、δ 3种受体,并且TH阳性细胞的数目明显多于多巴胺能SH-SY5Y细胞系.结论:MN9D细胞中同时存在μ、κ、δ3种阿片受体,可作为吗啡依赖细胞模型使用.     

阿片和阿片样物质耐受及成瘾的生化基础

阿片类制剂特别是吗啡具有较强的镇痛作用。但是反复使用时,它们的一些药理效应如:镇痛、降体温等便明显降低。只有增加药物剂量才能保持其原有的药理作用,这种现象称为耐受。反复使用还可造成机体对药物形成依赖性即成瘾,当突然停止药物使用或使用阿片受体阻断剂(如纳洛酮)阻断药物作用时,可以引起激惹、失眠、恶心、腹痛和衰弱等一系列戒断症状。在动物身上也可出现激惹、跳跃、腹泻、流涎、体重下降和体温降低等戒断行为     

免疫系统与神经内分泌系统之间的调节环路

<正> 一、前言:现已证明吗啡具有镇痛作用,并从脑组织中提出两类具有吗啡样作用的物质,人们称之为脑啡肽及内啡肽。1979年Wybran证明在人的T淋巴细胞上存在吗啡和甲硫脑啡肽的阿片受体,并同时发现吗啡抑制人活性T细胞花环的形成,而甲硫     

免疫细胞可塑性与免疫病理机制研究进展

免疫细胞是由造血干细胞发育分化而来,是免疫应答的主要执行者。在不同应激或免疫病理状态下,免疫细胞具有较强的可塑性潜能,能够转分化形成不同类型的免疫细胞亚群。转分化的免疫细胞执行特定的免疫功能,从而调控疾病的演进过程。近年来研究发现,终末分化的免疫细胞亚群之间能够互相转换,实现类型和功能的转变,即转分化。目前发现T细胞、固有淋巴样细胞、巨噬细胞和嗜中性粒细胞等均存在细胞类型转分化的现象,细胞的转分化调控着疾病的发生发展进程。免疫细胞的可塑性与感染、肿瘤和自身免疫性疾病等都有密切联系。因此,揭示免疫细胞的可塑性调控机制将为深入理解免疫相关疾病的发生发展进程提供重要的理论依据,并为疾病的干预提供新策略。本文拟将对免疫细胞可塑性的主要细胞类型、免疫细胞可塑性调节机制以及免疫细胞可塑性与疾病等作一综述。     

The two simultaneously occurring processes in one immune response: the positive immune reaction and immune tolerance

The immune response is tightly shaped by both positive and negative signals on different levels. Based on the accumulating data, we hypothesize that, both immune reaction and immune tolerance processes were potentially and simultaneously triggered after antigen challenging. The actual outcome of immune response is dependent on the sum of these two reactions. The hypothesis, if proved to be correct, will significantly improve our understanding the immunity and its related pathological effects. It will influence our choice on immunosuppressive drugs for patients with transplant grafts, autoimmune diseases. As the immunosuppressive drugs may also block the potential immune tolerance process which is beneficial to the patients. Therefore, we should try to develop novel immunosuppressive medicines that selectively inhibit immune reaction but no effects on immune tolerance for patients with allo-grafts or autoimmune diseases. On the other hand, it will impact the immunotherapy for tumors and the development of vaccines.     

流行性出血热病人血清和肾组织中存在IgE型免疫复合物

本文应用ELISA(双抗体夹心)法检测了EHF病人血清中IgE及其IgE型免疫复合物;应用免疫酶纽化法检测EHF尸体肾脏沉积的IgE型免疫复合物。结果发现各病日组病人血清中IgE和[gE型免疫复合物的含量显著地高于正常人。IgE水平以3～5病日者为最高,IgE型免疫复合物以6～10病日最高。EHF尸体肾脏组织中有IgE型免疫物沉积。这说明EHF病人血中有IgE型免疫复合物形成,可随血流沉积于肾组织,参与EHF中、晚期发病过程。     

A quantitative examination of the light scattering properties of immune complexes in polyethylene glycol

The effect of polyethylene glycol on the light scattering properties of immune complexes prepared in vitro was examined. Immune complexes were prepared in the zone of antigen excess from purified rabbit anti-ovalbumin and ovalbumin at 2-32 times (X) the equivalence ratio. Immune complex concentration was determined by analytical ultracentrifugation. Immune complexes were then incubated for 1 h in solutions containing 0, 1, 2, 3 and 4% polyethylene glycol (PEG), and examined in a laser nephelometer. The effect of PEG on light scattering (%RLS) was different for each immune complex combining ratio, although for each immune complex combining ratio, there was a linear relationship between the light scattered and immune complex concentration. To evaluate the effect of serum proteins on the light scattered by the immune complexes, immune complexes made at 4X and 16X the equivalence ratio were placed in serum and the sera containing these immune complexes were examined in the nephelometer. The ratio of the %RLS of the immune complexes in serum to the sum of the %RLS of the same immune complexes in saline plus the %RLS of serum alone was determined. This ratio varied systematically with changes in combining ratio and PEG concentration, as well as the concentration of the immune complexes themselves. Depending on the combination of these 3 factors, serum could increase, decrease or have no effect on the quantity of light scattered by the immune complexes. Discrimination between serum alone and serum containing immune complexes was best in 3% PEG.     

Immune response and corticosteroid content in different regimens of cooling

The effects of different cooling regimens modulating thermal afferent signal on the immune response were experimentally studied on rats. Immunization at low body temperature changed the immune response to the antigen. These changes depended on the depth and rate of previous cooling. The presence of dynamic activity of peripheral thermosensitive afferents potentiated the immune response after surface cooling and reduced the degree of suppression of the immune response after deep cooling. No clear-cut relationship between changes in the immune response and blood concentration of corticosterone during cooling was found.     

Immunological functions of the gut--role of the mucosal immune system

This review summarizes recent information about immune responses in the intestinal mucosa with emphasis on the role of orally-administered antigens from the external environment. The intestinal mucosa provides an extensive surface for potential absorption of pathogenic environmental antigens, such as microbes, chemicals, and food. The intestinal mucosa is densely populated by IgA-producing plasma cells. The humoral immune responses to antigens in the intestinal mucosa are largely of the IgA class in secretory form (sIgA). This sIgA provides an immunological barrier to absorption of antigens on the mucosal epithelium and to penetration into the body. The cell-mediated immune mechanism is also equipped in the mucosal sites. In addition, the mucosal immune response induces hyporesponsiveness of nonmucosal (systemic) immune reactions, and the liver is an integral part of the mucosal immune system. Thus we consider that the mucosal immune system plays a central role in the maintenance of the homeostasis of the total immune system.     

免疫血清、巨噬细胞及补体对体外培养旋毛虫肌幼虫的杀伤作用

为进一步了解旋毛虫成虫抗原免疫血清在体外对旋毛虫肌幼虫的杀伤情况 ,采用体外培养方法进行了免疫血清、免疫血清与巨噬细胞、免疫血清与巨噬细胞及补体对旋毛虫肌幼虫的杀伤试验。结果显示 :单纯免疫血清对体外培养的旋毛虫肌幼虫无明显杀伤作用 ,而免疫血清与巨噬细胞或免疫血清与巨噬细胞及补体联合对体外培养的旋毛虫肌幼虫均有杀伤作用 ,以免疫血清联合巨噬细胞及补体的作用最显著     

Tumor-induced immunosuppression

Tumor immunology is based on two essential concepts: immune surveillance, which implicate the host immune reactions against tumor cells, and tumor immune escape, which refers to the tumor-cell evasion process against the host immune system. The notion that a deficit in immune cell functions permits tumor growth has received experimental support with the discovery of several different biochemical defects in T lymphocytes that infiltrate cancers. Furthermore, expression of self-antigens on the tumor surface impose potential barriers to the development of effective immune response. Tumors are able to overcome immune surveillance by changing the polarity of effectors cells, thus down-regulating the proliferation of tumor-specific cytotoxic T cells, or altering the effector compositions of immune cells within the tumor milieu, or both. Understanding the interaction between cancer cells and host immune cells is of importance for clinical applications or immunotherapy in cancer treatment.     

Revisiting immunosurveillance and immunostimulation: Implications for cancer immunotherapy

Experimental and clinical experience demonstrates that the resolution of a pathogenic challenge depends not only on the presence or absence of an immune reaction, but also on the initiation of the proper type of immune reaction. The initiation of a non-protective type of immune reaction will not only result in a lack of protection, but may also exacerbate the underlying condition. For example, in cancer, constituents of the immune system have been shown to augment tumor proliferation, angiogenesis, and metastases. This review discusses the duality of the role of the immune system in cancer, from the theories of immunosurveillance and immunostimulation to current studies, which illustrate that the immune system has both a protective role and a tumor-promoting role in neoplasia. The potential of using chemotherapy to inhibit a tumor-promoting immune reaction is also discussed.     

Ovarian function and the immune system.

A hypothesis is presented on the interaction between the immune system and ovary in the regulation of the reproductive system and in the origin of some of its disorders. It has been suggested that the beginning, duration and age dependent failure of ovarian ovulatory function depends among other things on the adequate relationship between the immune system and approriate ovarian target structures. The cyclicity of ovarian function is considered to be primarily dependent on the induction of a specific cyclic immune response to the ovary. Similarly, the selection of a species-specific number of ovulating follicles during sexual maturity is thought to be ensured by immune mechanisms. This hypothesis, on the role of the immune system in regulation of ovulatory ovarian function respects the physiological effect of gonadotropins and steroids on the ovarian structures. The interaction between the ovary and the hypothalamus-pituitary system appears to be modulated by the relationship between the ovary and the immune system.