PPARγ在狼疮肾炎患者肾组织中的表达及其意义

目的观察过氧化物酶体增殖物激活受体γ(PPARγ)在狼疮肾炎(LN)不同病变类型肾组织中的表达及其与肾脏病理改变之间的关系,探讨PPARγ在LN发病机制中的可能作用。方法根据临床及肾活检病理诊断,选择LN不同病变类型患者作为研究对象,其中Ⅱ型(6例),Ⅳ型(8例),Ⅴ型(7例)。以肾脏肿瘤切除术中远离肿瘤部位的正常肾组织(6例)为对照。光镜下观察并计数肾脏病变活动指数、间质病变指数；用免疫组织化学方法对各例肾组织PPARγ的表达进行检测,并对其与肾脏病变的相关性进行分析。结果LN患者肾组织。肾小管、肾小球及间质浸润细胞中PPARγ脚表达较正常对照组均显著上调,其中Ⅳ型LN肾组织肾小管、肾小球及间质浸润细胞PPARγ表达显著高于Ⅱ型、Ⅴ型；肾小球PPARγ染色阳性细胞数目与肾脏病理活动积分及间质病变指数之间呈显著正相关(r=0．94；P＜0．01)。结论PPARγ在LN肾组织肾小管、肾小球及间质浸润细胞高表达对于限制LN肾脏病变发展可能具有重要作用     

肾脏病肾间质中淋巴细胞亚群浸润的意义

本文报告286例各种肾脏病肾间质中淋巴细胞亚群的分析结果.正常肾间质散在分布少量CD_4~+细胞、CD_~+细胞及B~+细胞.局灶节段硬化肾炎、膜增肾炎、IgA肾病、狼疮肾炎、结节性多动脉炎及多种间质小管疾病间质中CD_4~+细胞、CD_~+细胞及B~+细胞数量著增多,CD_4~+/CD_~+细胞比值在狼疮肾炎一般<1,IgA肾病大都>1;系膜增殖肾炎、糖尿病肾病及内皮系膜增殖肾炎的CD_4~+细胞、CD_~+细胞及B~+细胞轻度增加;遗传肾炎、原发肾炎的轻微病变、IgM肾病、膜性肾病及高血压肾损害者等其CD_4~+细胞、CD_~+细胞及B~+细胞数量接近正常.间质中的T细胞数量与小管萎缩、间质纤维化程度以及血清肌酐值呈正相关.结果表明,分析肾间质淋巴细胞亚群可能有助于肾脏病的诊断,有助于判断病情的严重程度.细胞免疫可能参与间质小管损伤.     

Defensinα1-3在狼疮肾炎患者肾组织中的表达及意义

目的探讨defensin α1-3在不同病理类型狼疮肾炎(LN)肾组织中的表达及意义.方法收集47例LN患者的肾活检的肾组织,包括世界卫生组织(WHO)Ⅱ型7例、Ⅲ型6例、Ⅳ型29例、Ⅴ型5例,以及11例泌尿外科手术切除的远离肿瘤的肾皮质区的肾组织作为正常对照,使用defensin α1-3单克隆抗体进行免疫组织化学染色,定量分析defensin α1-3在各个病理类型LN肾组织及正常肾组织中的表达及分布,并分别与相应的增殖细胞核抗原(PCNA)、肾小球病变活动指数(GAI)和肾间质病变活动指数(TIAI)进行相关性的分析.结果各个病理类型LN肾组织及正常肾组织的肾小球、肾间质中均有defensin α1-3的表达,其中肾小球的defensin α 1-3的表达在Ⅱ、Ⅲ、Ⅳ型LN组明显高于正常对照组,肾间质中defensin α1-3表达在Ⅳ型LN组高于其他类型的各组及正常对照组.Ⅳ型LN组的肾小球区域的defensin α1-3的表达与Ⅳ型LN组的肾小球区域的PCNA阳性细胞数(r=0.785,P＜0.05)、及GAI评分之间(r=0.749,P＜0.05)呈正性线性相关.Ⅳ型LN组的肾间质的defensin α 1-3的表达与其TIAI之间呈正性线性相关(r=0.767,P＜0.01).结论defensin α 1-3可能参与了Ⅳ型LN的发病.     

58例狼疮性肾炎病理与临床分析

目的 分析肾活检及相关实验室检测结果，探讨狼疮性肾炎（LN）病理类型与临床表现的关系。方法 对58例LN患者进行肾活检及常规实验室检查。根据WHO 1982年标准进行病理分型，并分别进行活动性指数（AI），慢性指数（CI）和肾小管间质病变（TIL）评分。结果 病理类型以Ⅳ型LN最多，占38％，其次Ⅱ型（26％）和Ⅴ型（24％），Ⅱ型与Ⅲ型多表现为肾炎综合征，Ⅳ型和Ⅴ型多表现为肾病综合征。Ⅳ型和LN的血,高血压，肾功能不全发生率最高，其AI亦显著高于其他类型。LN肾间质受累以Ⅳ型最为显著。血Cr水平与肾间质受累程度呈正相关。与TIL0－1级相比，2－3级病程相对要长。1－2级者尿蛋白排泄较0级与3级为高。结论 LN的病理类型与临床表现有一定关系，根据其临床表现和实验室检查可大致推测其病理类型。肾活检对判断疾病活动性，指导治疗与估计预后有重要意义。     

血栓调节蛋白检测在狼疮性肾炎血管病变中的意义

目的：探讨狼疮性肾炎(LN)患者血浆可溶性血栓调节蛋白(sTM)水平和肾组织TM免疫组化染色特点，分析其与系统性红斑狼疮活动度(SLEDAI)、血管病变、肾功能、蛋白尿、肾组织病理类型之间的关系。方法：60例经肾穿刺活检明确诊断的LN患者，采用酶联免疫吸附法(ELISA)检测血浆sTM水平，免疫组化染色检测肾小球和间质血管TM的表达。结果：Ⅱ型LN患者血浆sTM水平与正常对照组相近，Ⅳ型LN患者血浆sTM水平显著高于Ⅱ型LN；而合并有血栓性微血管病变的LN患者血浆sTM水平显著高于Ⅳ型LN，血浆sTM水平与狼疮的病变活动度和血清肌酐水平呈正相关，与蛋白尿多少无关。肾组织TM免疫组化染色示Ⅳ型LN肾小球与血管TM染色强度强于Ⅱ型LN；合并血栓性微血管病变LN患者肾小球与血管TM的染色强度与Ⅳ型LN相似。结论：血浆sTM水平与SLEDAI、血管病变轻重、肾功能损害程度及肾组织病变类型有关。肾小球和肾间质血管的TM表达强度与LN病理类型有关，但不能反映血管病变的轻重。血浆sTM水平不仅反映SLE疾病活动性，而且与LN的血管病变严重程度有关。血浆sTM水平可作为LN血管病变程度的指标，为指导治疗、判断预后提供依据。     

Bcl-2、Bax在狼疮肾炎患者肾组织中的表达及意义

目的研究细胞凋亡调节蛋白(Bcl-2及Bax)在狼疮肾炎(LN)患者肾组织的表达情况及与LN肾脏病理改变的关系。方法2003-012003-04对广西医科大学第一附属医院的44例活动期LN患者用免疫组化方法检测肾组织中Bcl-2、Bax的表达,观察它们与LN肾脏病理改变的关系。结果(1)LN肾小球Bcl-2及Bax表达均增高,与肾小球细胞增殖程度及增殖细胞核抗原(PCNA)阳性细胞数呈正相关。(2)LN肾间质Bcl-2表达增高,与间质炎症细胞浸润程度正相关。(3)LN肾小管Bax表达增高,与肾小管间质病变呈正相关。结论LN肾组织存在Bcl-2、Bax蛋白异常表达。Bcl-2高表达在LN肾小球细胞增殖及肾间质炎症细胞浸润过程中可能起重要作用。Bax在肾小管过度表达与肾小管间质病变有关。     

狼疮性肾炎患者白细胞介素-13的表达及其临床意义

目的 探讨狼疮性肾炎(LN)患者血浆及肾组织白细胞介素-13(IL-13)的表达及其临床意义。方法 采用ELISA法检测血浆IL-13水平，采用免疫组化ABC法检测肾组织IL-13的表达。结果 LN患者血浆IL-13水平、肾小球及肾小管间质区IL-13表达较对照组和非LN肾脏病对照组增高，以Ⅳ型LN患者肾小球区IL-13表达最高，而不同病理类型的LN肾小管间质区IL-13表达无显著性差异。LN患者血浆及肾小管间质区IL-13表达与Ccr和血清C3呈负相关，与肾小管间质病变活动指数和肾小球病变活动指数呈正相关。结论 IL-13参与LN的分子病理机制，血浆及肾组织IL-13水平可能有助于判断狼疮活动程度。     

肥大细胞与狼疮肾炎肾间质纤维化关系的初步探讨

目的初步探讨狼疮肾炎(LN)患者肾间质中肥大细胞(MCs)与肾间质纤维化之间的关系。方法随机选取Ⅲ、Ⅳ、V型LN患者各10例作为研究对象,微小病变病(MCD)患者11例作为对照组。采用免疫组织化学、免疫荧光双重染色方法观察肾组织中类胰蛋白酶(Try)染色阳性MCs、蛋白酶活化受体-2(PAR-2)、转化生长因子-β1(TGF-β1)及I型胶原(Col I)表达的变化。结果 3个LN组肾间质MCs数量、肾小管上皮细胞PAR-2和TGF-β1及肾间质Col I表达面积均较MCD对照组明显升高,其中Ⅳ型LN组上述4项指标增加最明显,Ⅲ型LN组次之。MCs数量与肾小管上皮细胞PAR-2、TGF-β1及肾间质Col I阳性染色面积呈显著正相关;肾小管上皮细胞PAR-2与TGF-β1阳性染色面积间呈显著正相关;MCs数量与肾间质PAR-2和TGF-β1阳性染色细胞数量分别呈显著正相关;PAR-2阳性染色细胞数量和TGF-β1阳性染色细胞数量间也呈显著正相关;肾间质中Try阳性染色细胞与PAR-2或TGF-β1 阳性染色细胞存在部分重叠。结论 MCs可能参与LN肾间质细胞外基质蓄积,推测可能与释放Try、活化PAR-2、增加TGF-β1表达相关。     

乙型肝炎病毒感染与狼疮肾炎肾小管间质病变的研究

目的对狼疮肾炎（LN）肾组织进行乙型肝炎病毒抗原（HBVAg）和HBVDNA的检测，并分析其与LN肾小管间质病变之间的关系。方法应用免疫组织化学二步法检测44例LN肾组织HB-VAg、T淋巴细胞和单核，巨噬细胞；应用荧光定量聚合酶链反应（FQ-PCR）技术对其中9例行肾组织HBVDNA检测。结果LN肾组织中HBVAg阳性率为59％（26／44）。LN肾组织中HBVDNA阴性的病例可检出44％（4／9）HBVAg。HBVAg阳性组肾小管间质中浸润的CD68’细胞数目显著高于阴性组（P〈0．05）及对照组（P〈0．01）。CD8＋细胞数目显著高于对照组（P〈0．05）。结论肾活检组织HBVAg阳性的LN临床上并非少见。LN肾组织HBVAg与肾小管间质病变的发生发展可能具有一定的关系。     

狼疮肾炎患者肾组织中结缔组织生长因子的转录表达及意义

目的探讨人类狼疮肾炎(LN)患者肾组织中结缔组织生长因子(CTGF)的基因转录和蛋白表达与肾纤维化之间的关系。方法应用免疫组织化学和原位杂交技术,以15例正常肾组织为对照,观察了36例LN患者肾组织中CTGF表达的分布和表达量的变化,分析肾组织中CTGF表达与LN肾间质病变的内在联系。结果LN患者肾组织的CTGF表达主要分布在肾小管上皮细胞和肾间质细胞、肾小球脏层和壁层上皮细胞和系膜区细胞。正常肾组织没有或只有极弱的CTGFmRNA转录和蛋白表达;LN患者肾组织CTGFmRNA转录及蛋白表达量较正常肾组织显著增高(CTGFmRNA:8.22±3.13比1.12±0.23;CTGF蛋白:8.74±3.24比1.21±0.22,P均<0.001);LN患者肾组织CTGF表达量与肾间质病变程度呈正相关(r=0.863,P<0.01);Ⅳ型LN患者肾组织CTGF表达量显著高于非Ⅳ型LN患者(CTGFmRNA:10.73±3.61比4.78±1.82CTGF蛋白:11.03±1.12比5.02±1.31,P均<0.01);CTGF的蛋白表达量与转化生长因子(TGF)-β1、纤维结合蛋白(Fn)及ColⅢ的表达量呈正相关(r=0.704、r=0.783及r=0.756,P均<0.01)。结论CTGFmRNA转录和蛋白表达量的增加与LN患者肾小管间质病变程度加重呈正相关。作为TGF-β的下游介质,CTGF可通过促进细胞外基质如FN和ColⅢ等合成,从而在LN患者肾小球硬化及肾小管间质纤维化的     

Three layer functional model and energy exchange concept of aging process

Relying on a certain degree of abstraction, we can propose that no particular distinction exists between animate or living matter and inanimate matter. While focusing attention on some specifics, the dividing line between the two can be drawn. The most apparent distinction is in the level of structural and functional organization with the dissimilar streams of ‘energy flow’ between the observed entity and the surrounding environment. In essence, living matter is created from inanimate matter which is organized to contain internal intense energy processes and maintain lower intensity energy exchange processes with the environment. Taking internal and external energy processes into account, we contend in this paper that living matter can be referred to as matter of dissipative structure, with this structure assumed to be a common quality of all living creatures and living matter in general. Interruption of internal energy conversion processes and terminating the controlled energy exchange with the environment leads to degeneration of dissipative structure and reduction of the same to inanimate matter, (gas, liquid and/or solid inanimate substances), and ultimately what can be called ‘death.’ This concept of what we call dissipative nature can be extended from living organisms to social groups of animals, to mankind. An analogy based on the organization of matter provides a basis for a functional model of living entities. The models relies on the parallels among the three central structures of any cell (nucleus, cytoplasm and outer membrane) and the human body (central organs, body fluids along with the connective tissues, and external skin integument). This three-part structural organization may be observed almost universally in nature. It can be observed from the atomic structure to the planetary and intergalactic organizations. This similarity is corroborated by the membrane theory applied to living organisms. According to the energy nature of living matter and the proposed functional model, the decreased integrity of a human body's external envelope membrane is a first cause of the structural degradation and aging of the entire organism. The aging process than progresses externally to internally, as in single cell organisms, suggesting that much of the efforts towards the restoration and maintenance of the mechanisms responsible for structural development should be focused accordingly, on the membrane, i.e., the skin. Numerous reports indicate that all parts of the human body, like: bones, blood with blood vessels, muscles, skin, and so on, have some ability for restoration. Therefore, actual revival of not only aging tissue of the human body's membrane, but the entire human body enclosed within, with all internal organs, might be expected. We assess several aging theories within the context of our model and provide suggestions on how to activate the body's own anti-aging mechanisms and increase longevity. This paper presents some analogies and some distinctions that exist between the living dissipative structure matter and inanimate matter, discusses the aging process and proposes certain aging reversal solutions.     

Unusual responses of nocturnal pineal melatonin synthesis and secretion to swimming: Attempts to define mechanisms

Abstract: The effect of swimming at night on rat pineal melatonin synthesis was compared with that of light exposure at night. Rats were forced to swim at 0030 hr (lights out at 2000 hr) and sacrificed by decapitation 15 and 30 min later, immediately after swimming. Other groups of animals were exposed to white light (650μW/cm²) for 15 and 30 min at same time. Swimming caused a rapid and highly significant drop in the melatonin content in the pineal gland; however, the activity of N-acetyltransferase (NAT), the supposed rate limiting enzyme in the melatonin production, was not changed. Despite the drop in pineal melatonin levels, serum concentrations of the indole remained elevated in the rats that swam. In contrast, melatonin levels in the pineal and serum of light exposed rats fell precipitously, accompanied by a significant suppression of NAT activity. Since we anticipated that the strenuous exercise associated with swimming may induce release of artrial natriuretic peptide (ANP) from the heart, which in turn could cause the release of pineal melatonin, in a second study we injected physiological saline intravenously to stretch the cardiac muscle and release ANP. Three milliliters of normal saline was injected during the day into the jugular vein of anesthetized rats that were pretreated with isoproterenol to stimulate pineal melatonin production. Animals were killed 15 min after the saline injection, and pineal NAT activity and pineal melatonin levels were measured. The saline injections caused no alteration in the elevated levels of either NAT or melatonin. These data suggest that the disparity in pineal NAT activity (which was high) and pineal melatonin (which was low), in animals swum at night, may not be caused by ANP which is released during strenuous exercise such as swimming.     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Melatonin and photoperiodic time measurement: Seasonal breeding in the sheep

Abstract: Well-established circadian physiology supports the view that photoperiodic time measurement utilizes the coincidence between the presence of light and a photosensitive phase of a 'biological clock' to alter reproductive status—the so-called external coincidence model of seasonal breeding. In this review, we examine the mechanism whereby photoperiod interacts with presumed suprachiasmatic nuclei activity to allow endogenous melatonin to normally synchronize reproductive activity to the optimal time of year. The Romney Marsh sheep is particularly explored as an experimental model. It is suggested that the on/off activity of seasonal reproduction may be a robust mechanism able to be predictably manipulated by the judicious use of the light/dark cycle and exogenous melatonin, but firmly based on circadian principles.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.