美沙拉嗪对2，4，6-三硝基苯磺酸诱导溃疡性结肠炎大鼠脾脏组织NF—κBp65表达的影响

目的 探讨美沙拉嗪对2,4,6-三硝基苯磺酸（TNBS）诱导的溃疡性结肠炎大鼠脾脏组织NF-κB p65表达的影响.方法 将42只SD大鼠随机分为空白对照组、结肠炎模型组和美沙拉嗪治疗组,每组各14只.除空白对照组外,其他两组均应用TNBS灌肠制作溃疡性结肠炎大鼠模型;模型建成2d后,空白对照组和结肠炎模型组均用蒸馏水、美莎拉嗪治疗组用美莎拉嗪蒸馏水混悬液3 mL灌胃;连续灌胃15 d后取脾脏组织,采用RT-PCR法检测NF-κB p65 mRNA,Western blot法检测NF-κB p65蛋白.结果 与空白对照组比较,结肠炎模型组NF-κB p65 mRNA、蛋白表达均升高（P均＜0.05）;与结肠炎模型组比较,美沙拉嗪治疗组NF-κB p65 mRNA、蛋白均下降（P均＜0.05）.结论 美沙拉嗪能通过下调TNBS诱导的溃疡性结肠炎大鼠脾脏组织NF-κB p65的表达,发挥治疗溃疡性结肠炎的作用.     

维药西帕依溃结安对大鼠溃疡性结肠炎模型组织中c-jun表达的影响

目的:探讨维药西帕依溃结安对溃疡性结肠炎模型大鼠结肠组织中即刻早期原癌基因c-jun表达的影响.方法:采用2, 4-二硝基氯苯(DNCB)与乙酸复合法制备大鼠溃疡性结肠炎模型, 分为5组进行实验. 应用RT-PCR和Western blot方法分别检测各组c-jun mRNA及其蛋白质表达.结果:在对大鼠溃疡性结肠炎模型治疗中, 维药西帕依溃结安大剂量治疗组中c-jun的蛋白质表达水平与生理盐水阴性对照组及5-氨基水杨酸组相比均明显下调, 差异有统计学意义(0.50±0.14 vs 0.84±0.44, 0.79±0.17, 均P <0.05).结论:维药西帕依溃结安可能是通过在转录后水平上降低c-jun在结肠中的表达来促进溃疡性结肠炎的愈合.     

安肠愈疡汤对溃疡性结肠炎大鼠结肠组织中TFF3、MUC2和TLR4基因表达的影响

背景:TLR4可介导免疫和炎症反应,TFF3、MUC2为肠黏膜保护因子,维持肠黏膜屏障功能。目的:观察安肠愈疡汤对溃疡性结肠炎大鼠结肠组织中TFF3、MUC2和TLR4基因表达的影响。方法:应用TNBS制备溃疡性结肠炎大鼠模型。将90只Wistar大鼠随机分为空白对照组、模型组、安肠愈疡汤低、中、高剂量组和美沙拉嗪组,分别给予蒸馏水、不同剂量安肠愈疡汤和美沙拉嗪。21 d后处死大鼠,行结肠黏膜组织病理学评分,采用RT-PCR法检测结肠组织中TFF3、MUC2和TLR4基因表达。结果:与模型组相比,安肠愈疡汤中、高剂量组和美沙拉嗪组组织病理学评分、TLR4表达均显著降低(P0.05),TFF3、MUC2表达均显著升高(P0.05)。与安肠愈疡汤中剂量组相比,安肠愈疡汤高剂量组和美沙拉嗪组组织病理学评分显著降低(P0.05),TFF3表达显著升高(P0.01)。与安肠愈疡汤中剂量组和美沙拉嗪组相比,安肠愈疡汤高剂量组MUC2表达显著升高(P0.01),TLR4表达显著降低(P0.01)。结论:安肠愈疡汤可明显促进溃疡性结肠炎大鼠结肠黏膜修复,其作用机制可能与上调TFF3和MUC2基因表达以及下调TLR4基因表达有关。     

久泻灵颗粒对脾肾阳虚型溃疡性结肠炎大鼠IL-2、IL-4、IL-10表达的影响

目的探讨不同剂量久泻灵颗粒治疗前后脾肾阳虚型溃疡性结肠炎大鼠血清及结肠中白细胞介素(IL)-2、IL-4、IL-10及其基因表达的变化。方法大黄水煎液灌胃+肌注氢化可的松+三硝基苯磺酸(TNBS)/乙醇灌肠法复建动物模型。90只Wistar大鼠随机分为空白组、模型组、久泻灵颗粒高、中、低剂量组及柳氮磺吡啶(SASP)组,药物干预后,镜下观察病理组织学变化进行评分,采用酶联免疫法检测各组大鼠血清中IL-2、IL-4、IL-10含量,RT-q PCR法检测基因表达。结果相比空白组,模型组大鼠血清中IL-2、IL-4、IL-10含量及结肠组织中的基因表达均降低(P<0.05);相比模型组,各治疗组大鼠血清中IL-2、IL-4、IL-10含量及结肠组织中的基因表达均升高(P<0.05),作用最显著的是久泻灵颗粒高剂量组(P<0.05)。结论久泻灵颗粒调节免疫活性,促进脾肾阳虚型溃疡性结肠炎模型大鼠血清中IL-2、IL-4及IL-10的分泌,从而抑制炎症发生,保护结肠黏膜。     

青黛颗粒对溃疡性结肠炎大鼠结肠黏膜MUC2和iNOS基因表达的影响

目的:观察青黛颗粒对TNBS诱导的溃疡性结肠炎(UC)大鼠结肠黏膜黏蛋白(MUC2)及诱导型一氧化氮合成酶(iNOS)基因表达的影响,探讨其治疗UC的可能作用机制.方法:将54只SD实验大鼠随机分为正常对照组、模型对照组、阳性药物治疗组(SASP,500 mg/kg)、青黛颗粒600、900、1 200 mg/kg治疗组.造模后第3天开始灌胃给药,共给药10d.实验第14天,处死大鼠,剖取其病变结肠组织,比较各组大鼠的DAI积分和CMDI评分,用逆转录聚合酶链反应(RT-PCR)法检测MUC2及iNOS基因的表达.结果:较模型组青黛颗粒900、1200 mg/kg治疗组能显著降低实验大鼠DAI积分和CMDI评分,上调结肠组织中MUC2的基因表达(2.06±0.70 vs 1.24±0.47;2.34±0.86 vs 1.24±0.47.均P<0.01),且青黛颗粒1 200 mg/kg治疗组能下调iNOS的基因表达(0.35±0.12vs 0.62±0.31.P<0.05).结论:青黛颗粒可能通过上调结肠黏膜MUC2的基因表达并下调iNOS的基因表达而起到抗TNBS诱导的大鼠溃疡性结肠炎的作用.     

溃疡性结肠炎癌变和丁酸的预防作用

溃疡性结肠炎(UC)是一种病因不明,主要累及直肠、乙状结肠黏膜甚至全结肠和末端回肠黏膜的慢性非特异性炎症。UC患者发生结直肠癌的风险增加,但其癌变机制尚不清楚。近年来,体外研究和动物实验均证实丁酸对结直肠癌具有化学预防作用。本文就UC的癌变机制、丁酸对结直肠癌的预防作用及其与UC相关结直肠癌的关系作一综述。     

STAT6 mRNA与NF-kB在实验性结肠炎大鼠中的表达

目的 研究信号转导和转录激活因子6 (STAT6 )与核因子(NF)-κB在实验性结肠炎大鼠中的表达.方法 18只SD雄性大鼠随机分为3组:正常对照组、模型组、美沙拉嗪组.每组6只.模型组和美沙拉嗪组大鼠均采用三稍基苯磺酸(TNBS)造模.模型组不设干预.正常饮食;美沙拉嗪组给予美沙拉嗪混悬液灌胃;治疗15d后观察大鼠的结肠病理组织学改变,用RT-PCR法检测大鼠结肠组织STAT6 rnRNA的表达,并用Western Blot法检测大鼠脾淋巴细胞NF-κB p65的表达.结果 STAT6 mRNA在溃疡性结肠炎组织中的表达明显高于正常结肠组织(P<0.01);大鼠脾淋巴细胞NF-κB p65蛋白在模型组的表达也明显高于正常组(P<0.01);与模型组相比.美沙拉嗪组STAT6 mRNA和NF-κB p65的表达明显下降(P<0.01).结论 STAT6 rnRNA和NF-κB p65在实验性结肠炎大鼠中呈现高表达.美沙拉嗪可能是通过STAT6和NF-κB双信号途径下调炎症,从而发挥治疗作用.     

低剂量131Ⅰ标记的抗癌胚抗原抗体C50联合化疗诱导裸鼠结直肠癌移植瘤细胞凋亡

目的从诱导细胞凋亡的角度,探讨低剂量131Ⅰ标记的抗癌胚抗原(CEA)单抗C50(131Ⅰ-C50)对结直肠癌移植瘤的治疗作用及联合5-氟尿嘧啶(5-FU)化疗的效果.方法建立表达CEA的人LoVo结直肠癌荷瘤裸鼠模型.接种第9天,分别采用5-FU、75μ131I-C50及5-FU联合131IC50尾静脉注射治疗裸鼠移植瘤.接种第15天,肿瘤组织进行HE染色和末端脱氧核糖核酸转移酶介导的荧光素-dUTP缺口末端标记法(TUNEL法)凋亡细胞染色,计算肿瘤细胞凋亡指数.结果光学显微镜下各组裸鼠移植瘤组织未见细胞溶解、坏死表现.TUNEL法染色示空白对照组、化疗组、放射免疫治疗(RAIT)组及RAIT+化疗组的凋亡指数分别为(0.29±0.08)%,(18.68±2.69)%,(40.88±4.54)%和(62.33±8.00)%,各组两两之间凋亡指数差异均有显著性(P值均＜0.001).结论低剂量RAIT可通过诱导肿瘤细胞凋亡达到治疗结直肠癌的目的,RAIT联合5-FU化疗可明显增强诱导肿瘤细胞凋亡的效果.     

STAT6 mRNA与NF-κB在实验性结肠炎大鼠中的表达

目的研究信号转导和转录激活因子6(STAT6)与核因子(NF)-κB在实验性结肠炎大鼠中的表达。方法 18只SD雄性大鼠随机分为3组:正常对照组、模型组、美沙拉嗪组,每组6只。模型组和美沙拉嗪组大鼠均采用三硝基苯磺酸(TNBS)造模。模型组不设干预,正常饮食;美沙拉嗪组给予美沙拉嗪混悬液灌胃;治疗15d后观察大鼠的结肠病理组织学改变,用RT-PCR法检测大鼠结肠组织STAT6mRNA的表达,并用Western Blot法检测大鼠脾淋巴细胞NF-κBp65的表达。结果 STAT6 mRNA在溃疡性结肠炎组织中的表达明显高于正常结肠组织(P0.01);大鼠脾淋巴细胞NF-κBp65蛋白在模型组的表达也明显高于正常组(P0.01);与模型组相比,美沙拉嗪组STAT6 mRNA和NF-κBp65的表达明显下降(P0.01)。结论 STAT6 mRNA和NF-κB p65在实验性结肠炎大鼠中呈现高表达。美沙拉嗪可能是通过STAT6和NF-κB双信号途径下调炎症,从而发挥治疗作用。     

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.     

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.     

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.     

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.     

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.     

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.