升阳益胃汤对糜烂性胃炎患者HGF/c-Met信号通路的影响

目的 研究升阳益胃汤对慢性糜烂性胃炎患者肝细胞生长因子(HGF)/HGF受体(c-Met)信号通路的影响。方法纳入2017年2月至2019年2月于东莞市第三人民医院收治的100例慢性糜烂性胃炎患者为对象,按照抽签随机方法分为两组,各50例。其中对照组予以阿拉坦五味丸治疗,观察组实施升阳益胃汤治疗,均持续治疗24周。观察两组治疗前后血清HGF表达水平,比较两组胃黏膜组织内HGF、c-Met表达水平,分析胃黏膜组织中HGF与c-Met的相关性及血清HGF与胃黏膜组织HGF的相关性。结果 两组治疗后血清HGF表达水平、胃黏膜组织内c-Met表达水平均显著低于治疗前(P 0. 05),且观察组治疗后血清HGF表达水平、胃黏膜组织内c-Met表达水平均显著低于对照组(P 0. 05)。观察组治疗后胃黏膜组织内HGF表达水平显著低于治疗前及对照组治疗后(P 0. 05)。慢性糜烂性胃炎患者胃黏膜组织中HGF与c-Met呈正相关性(r=0. 898,P=0. 000),胃黏膜组织HGF与血清HGF呈正相关性(r=0. 889,P=0. 000)。结论 升阳益胃汤能显著降低糜烂性胃炎患者血清HGF和胃黏膜组织HGF、c-Met表达,临床应引起足够重视。     

左金丸及其拆方对萎缩性胃炎大鼠胃黏膜HSP70基因表达的影响

[目的]阐明左金丸及其拆方对萎缩性胃炎大鼠胃黏膜HSP70基因表达的影响。[方法]建立CAG大鼠模型,并随机分为模型、替普瑞酮、黄连、吴茱萸、左金丸组,设立空白和假手术组,治疗1月后,各组取三只,实时定量PCR法测定各组大鼠胃黏膜中Hsp70mRNA表达量,Western blot法测定Hsp70/Hsp72蛋白表达量,余大鼠HE法观察胃黏膜病理变化。[结果]模型组与其他各组比较,其胃黏膜体积构成比明显下降(P0.01)。各治疗组均可以提高胃黏膜体积构成比,但各组间无差异。吴茱萸及左金丸组与模型组相比可以显著增高HSP70mRNA水平(P0.05)。在蛋白水平,各治疗组蛋白的表达高于模型组,但与模型组比较差异无统计学意义(P0.05)。[结论]中药吴茱萸及左金丸可以改善萎缩性胃炎大鼠胃黏膜的萎缩状态,诱导热休克蛋白70基因表达可能是其治疗萎缩性胃炎的作用机制之一。     

AIF和HSP70在胃息肉及胃癌中的表达及其相关性研究

目的检测凋亡诱导因子(AIF)及热休克蛋白70(HSP70)mRNA在胃癌及胃息肉中的表达,探讨其对胃癌的发生、发展的影响。方法收集内蒙古医科大学第三附属医院120例活检标本,依据病理分为胃增生性息肉组、胃腺瘤性息肉组、胃癌组、正常胃黏膜组,每组30例。采用实时荧光定量PCR检测相应胃黏膜组织中AIF mRNA与HSP70 mRNA的表达水平。结果在胃增生性息肉、胃腺瘤性息肉及胃癌组织中,AIF及HSP70 mRNA的表达呈逐渐上升趋势,差异有统计学意义(P0.05);在胃腺瘤性息肉组及胃癌组中,AIF mRNA与HSP70 mRNA的表达呈正相关(P0.01)。结论 AIF及HSP70基因可能与胃癌形成有关,均可作为胃癌早期诊断的临床指标,AIF mRNA和HSP70 mRNA可能在胃癌的形成及发展过程中发挥协同作用,可能为基因的协同治疗提供新靶点。     

血清热休克蛋白及氧化损伤指标与慢性心力衰竭患者疾病严重程度的关系探究

目的探究血清热休克蛋白(HSP)及氧化损伤指标与慢性心衰患者疾病严重程度的关系。方法选取我院2019年5月至2020年5月接收的88例慢性心衰患者作为研究组,另选取同期88例健康志愿者作为对照组,两组患者均进行HSP、丙二醛(MDA)、一氧化氮(NO)、脂质过氧化物(LPO)检测。应用心力衰竭(NYHA)分级将研究组88例患者划分为:27例为Ⅱ级(组),32例为Ⅲ级(组),29例为Ⅳ级(组)。结果研究组HSP、氧化损伤指标水平高于对照组(P0.05);Ⅳ级HSP、MDA、NO、LPO水平高于Ⅱ级、Ⅲ级,Ⅲ级MDA水平高于Ⅱ级(P0.05),Ⅲ级HSP、NO、LPO水平略高于对照组,差异无统计学意义(P0.05);三组间HSP、MDA、NO、LPO水平对比,差异有统计学意义(P0.05);应用Spearman处理可得,HSP、MDA、NO、LPO水平与NYHA分级呈正相关(r=0.353、0.381、0.382、0.261,P=0.007、0.004、0.002、0.011)。结论 HSP及氧化损伤指标与慢性心衰患者的疾病严重程度有明显的正相关性     

聚普瑞锌诱导HSP70保护大鼠胃黏膜损伤

目的探讨聚普瑞锌诱导热休克蛋白70(heat shock protein 70,HSP70)减轻大鼠胃黏膜损伤的作用机制。方法无水乙醇灌胃致大鼠胃黏膜损伤后分别应用聚普瑞锌100 mg/kg、200 mg/kg灌胃及赋形剂灌胃,同时以空白组作对照,检测胃黏膜HSP70蛋白表达。同时检测各实验组大鼠胃黏膜IGF-1含量和SOD活性。结果聚普瑞锌100 mg/kg治疗组治疗3 d时HSP70表达的相对灰度值为278.3%±10.8%;聚普瑞锌200 mg/kg治疗组治疗3 d时HSP70表达的相对灰度值为471.1%±24.7%,与空白组和赋形剂组相比,差异均有统计学意义(P0.01)。各实验组大鼠胃黏膜IGF-1含量和SOD活性差异无统计学意义(P0.05)。结论聚普瑞锌能够诱导损伤后大鼠胃黏膜产生大量HSP70,发挥保护胃黏膜的作用。     

心肌热休克蛋白70在慢性心力衰竭患者中的表达

目的:观察慢性心力衰竭患者心肌热休克蛋白(HSP70)的表达。方法: 60例手术患者分为3组，其中心功能1级组20例，心功能2级组20例，心功能3级组20例。采用实时荧光定量（RT-PCR）方法检测HSP70的mRNA表达量。结果:①与心功能1级患者比较，HSP70 mRNA 水平在心功能2级、心功能3级组的心肌组织中表达明显减少（均P<0.05），且在心功能3级组较心功能2级组明显减少（P<0.05）。②HSP70 mRNA水平与慢性心力衰竭患者年龄、病程呈负相关。结论:慢性心力衰竭患者心肌HSP70的表达减少，可能与HSP70随着心功能恶化其保护作用减弱有关。     

艾灸足三里和梁门穴诱导热休克蛋白70抗大鼠胃黏膜氧化损伤作用

目的:观察艾灸足三里和梁门穴对应激性溃疡大鼠胃黏膜热休克蛋白70(HSP70)表达的影响,探讨艾灸足阳明经穴抗胃黏膜氧化损伤的作用机制.方法:将SD大鼠60只完全随机平均分为空白组、模型组、艾灸足三里等穴组和艾灸非穴对照点组,采用水浸-束缚应激法制备应激性溃疡模型.按Guth法计算胃黏膜损伤指数(UI),用激光多普勒血流仪测定胃黏膜血流量(GMBF),用免疫组织化学法和硫代巴比妥酸染色法对处理后大鼠检测其胃黏膜HSP70的表达和丙二醛(MDA)的含量.结果:与模型组和艾灸非穴组比较,艾灸足三里等穴可使应激性溃疡大鼠胃黏膜损伤指数明显下降(14.100±5.425vs26.800±9.807,26.200±7.729,P<0.01),HSP70表达上调(0.133±0.035vs0.077±0.057,0.059±0.038,P<0.01)、血流量增高(279.827±172.862mL/minvs139.489±33.133,141.512±58.450mL/min,P<0.05)、MDA含量减少(2.586±0.252μmol/Lvs3.906±0.768,3.464±1.502μmol/L,P<0.05).结论:艾灸足三里和梁门穴能诱导胃黏膜HSP70高表达并降低MDA含量,以达到其抗氧化损伤作用,并有相对的穴位特异性.     

隆起糜烂性胃炎证型与幽门螺杆菌感染及热休克蛋白60和70表达的相关性

[目的]探讨隆起糜烂性胃炎(Raised Erosive Gastritis,REG)中医证型与幽门螺杆菌(Hp)感染和病理组织学及热休克蛋白60(HSP60)、热休克蛋白70(HSP70)表达的关系,以期指导中西医结合防治REG。[方法]选择131例REG患者按中医辨证分为脾胃湿热证32例(Hp阳性19例,阴性13例),脾胃气虚证52例(Hp阳性者34例,阴性18例),脾虚湿热证47例(Hp阳性者33例,阴性14例)。所有受试者均行胃镜检查,取胃窦部活检标本行快速尿素酶试验及组织染色法检测Hp;病理组织学检查及免疫组织化学检测HSP60,其中63例免疫组织化学检测HSP70。并设正常对照(正常)组18例。[结果]REG脾虚湿热证组的萎缩、肠化生(IM)程度均高于脾胃湿热证及脾胃气虚证组(P0.05),而后2组之间比较以及3组中Hp阳性者与阴性者比较差异均无统计学意义(P0.05)。3组HSP60表达均较正常组增加(P0.01),而3组之间比较均P0.05;脾胃湿热证及脾虚湿热证组中Hp阳性者的HSP60表达均高于Hp阴性者(P0.05),而脾胃气虚组中的Hp阳性与Hp阴性者比较P0.05。3组的HSP70表达均较正常组增加(P0.01);而3组的HSP70阳性表达情况分别比较均P0.05;脾胃湿热证组中Hp阴性的HSP70表达高于Hp阳性者(P0.05),而脾胃气虚证组与脾虚湿热证组中Hp阳性者与阴性者HSP70表达比较均P0.05。REG Hp阳性者胃黏膜HSP60的表达明显高于Hp阴性(P0.01);REG Hp阳性者胃黏膜HSP70的表达与Hp阴性者比较P0.05。[结论]REG脾虚湿热证患者胃黏膜萎缩、IM程度均高于脾胃气虚证及脾胃湿热证。REG3组胃黏膜HSP60及HSP70的表达均较正常组增强。Hp感染可诱导胃黏膜HSP60的高表达。HSP60表达既与Hp感染有关,又与湿热之邪有关。     

丙氨酰谷氨酰胺对急性ST段抬高型心肌梗死患者PCI术后心功能的影响分析

目的探讨丙氨酰谷氨酰胺对急性ST段抬高型心肌梗死(STEMI)患者经皮冠状动脉介入治疗(PCI)术后心功能的影响及可能机制分析。方法纳入2015年10月至2018年10月于中部战区空军医院心内科行急诊PCI的STEMI患者60例为研究对象,按随机数字表法分为对照组(n=30)和观察组(n=30)。对照组患者采用STEMI常规治疗药物,观察组在对照组的基础上于术前及术后按0.5 g/kg体重静滴注射用丙氨酰谷氨酰胺,1/d,持续14 d。两组患者于术前、术后7 d、术后14 d抽血运用全自动生化分析仪检测N末端B型脑钠肽前体(NT-pro BNP)水平;双抗体夹心ELISA法检测血清热休克蛋白70(HSP70)浓度;采用比色法测血清中丙二醛(MDA)、超氧化物歧化酶(SOD)含量。HD15型彩色多普勒超声诊断仪检查左心室射血分数(LVEF)及二尖瓣舒张早期血流峰值(E)/二尖瓣舒张晚期血流峰值(A)变化。分析比较两组患者术前、术后7 d、术后14d NT-proBNP水平、HSP70浓度、SOD、MDA含量、LVEF、E/A比值变化情况。结果术前,两组患者LVEF、E/A、血浆NT-proBNP、血清HSP70、SOD、MDA比较,差异均无统计学意义(P0.05)。与术前相比,两组患者PCI术后7 d、14 d LVEF、E/A升高,而血浆NTpro BNP下降,差异均有统计学意义(P0.05);与术前相比,对照组PCI术后7 d、14 d,血清HSP70浓度较术前下降,差异有统计学意义(P0.05),观察组血清HSP70浓度较术前升高,差异有统计学意义(P0.05);与术前相比,两组患者PCI术后7 d、14 d血清SOD含量较术前均升高,差异有统计学意义(P0.01),而血清MDA含量下降,差异有统计学意义(P0.05)。与对照组相比,观察组PCI术后7 d、14d LVEF、E/A升高,而血浆NT-proBNP降低,差异均有统计学意义(P0.05);与对照组相比,观察组PCI术后7 d、14 d血清HSP70、SOD浓度升高,而血清MDA含量下降,差异均有统计学意义(P0.05)。相关性分析结果表明:血清HSP70、SOD浓度与LVEF、E/A呈正相关(P0.01),与血浆NT-proBNP呈负相关(P0.01);血清MDA浓度与LVEF、E/A呈负相关(P0.01),与血浆NT-proBNP呈正相关(P0.01)。结论丙氨酰谷氨酰胺能够减轻STEMI患者PCI术后心肌缺血再灌注损伤,改善心功能。其机制可能与诱导HSP70表达、降低MDA,升高SOD,增强心肌细胞的抗氧化能力,减轻自由基的损伤有关。     

表皮生长因子及其受体在糜烂胃黏膜中的表达

目的:观察胃窦黏膜糜烂区与糜烂旁胃黏膜、慢性萎缩性胃炎中表皮生长因子(epidermal growth factor,EGF)及其受体(epidermal growth factor receptor,EGFR)的表达,探讨其在胃黏膜损伤修复中的意义.方法:选择经胃镜及病理确诊的慢性萎缩性胃炎伴胃窦黏膜糜烂患者50例,距糜烂区3cm处40例,无糜烂慢性萎缩性胃炎40例,采用免疫组织化学染色法测EGF及EGFR的表达.结果:胃窦黏膜糜烂区EGF、EGFR阳性表达率分别为40%和30%,明显高于糜烂旁胃黏膜15%和10%及无糜烂慢性萎缩性胃炎20%和12.5%的阳性表达率(P<0.05),有统计学意义,无糜烂慢性萎缩性胃炎组略高于糜烂旁胃黏膜组,但无统计学差异.结论:EGF、EGFR在胃黏膜损伤后高表达,对促进胃黏膜修复有着重要意义.     

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.     

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.