依那普利不对DOCA-盐诱导的高血压大鼠发生影响

目的观察依那普利对DOCA-盐诱导的高血压大鼠(DHR)血压、主动脉结构、血浆内皮素(ET-1)和主动脉组织ET-1 mRNA表达的影响,并探讨依那普利不影响其变化的可能机制.方法 30只SD大鼠,等分和制作为正常对照组、模型对照组、依那普利组.依那普利组给予依那普利20 mg·kg-1·d-1灌胃.每周测血压一次.四周后处死,抽动脉血放免法测血浆ET-1浓度、肾素活性(PRA),取主动脉分别作病理分析和RT-PCR检测ET-1 mRNA表达.结果模型对照组血压明显上升,血管平滑肌细胞(VSMC)肥大,弹力纤维层增厚,中层厚度及中层厚度/内径明显增大.依那普利组血压也明显上升,四周后仅比模型对照组低9mmHg,两者相比差别无统计学意义,主动脉亦明显重塑.血浆肾素活性模型对照组和依那普利组显著低于正常对照组;依那普利组与模型对照组相比无差别;血浆ET-1及ET-1 mRNA表达模型对照组和依那普利组显著高于正常对照组;依那普利组与模型对照组相比无差别.结论依那普利不能改善DHR主动脉重塑,可能是DHR主动脉局部肾素-血管紧张素系统(RAS)受到抑制,低水平的RAS对血管组织增殖无重要作用.     

依那普利不对DOCA-盐诱导的高血压大鼠发生影响

目的　观察依那普利对DOCA -盐诱导的高血压大鼠 (DHR)血压、主动脉结构、血浆内皮素 (ET 1)和主动脉组织ET 1mRNA表达的影响 ,并探讨依那普利不影响其变化的可能机制。方法　 3 0只SD大鼠 ,等分和制作为正常对照组、模型对照组、依那普利组。依那普利组给予依那普利 2 0mg·kg- 1 ·d- 1 灌胃。每周测血压一次。四周后处死 ,抽动脉血放免法测血浆ET -1浓度、肾素活性 (PRA) ,取主动脉分别作病理分析和RT -PCR检测ET 1mRNA表达。结果　模型对照组血压明显上升 ,血管平滑肌细胞 (VSMC)肥大 ,弹力纤维层增厚 ,中层厚度及中层厚度 /内径明显增大。依那普利组血压也明显上升 ,四周后仅比模型对照组低 9mmHg ,两者相比差别无统计学意义 ,主动脉亦明显重塑。血浆肾素活性 :模型对照组和依那普利组显著低于正常对照组 ;依那普利组与模型对照组相比无差别 ;血浆ET 1及ET 1mRNA表达 :模型对照组和依那普利组显著高于正常对照组 ;依那普利组与模型对照组相比无差别。结论　依那普利不能改善DHR主动脉重塑 ,可能是DHR主动脉局部肾素 -血管紧张素系统 (RAS)受到抑制 ,低水平的RAS对血管组织增殖无重要作用     

非选择性内皮素受体拮抗剂波生坦对DOCA-盐型高血压大鼠心脏微小血管密度的影响

目的观察波生坦对DOCA(脱氧皮质酮)-盐型高血压大鼠(DHR)血压、血浆内皮素-1(ET-1)浓度和左心室内膜下心肌间微小血管密度的影响,探讨ET-1在其病理机制中的可能作用.方法 18只清洁级雄性SD大鼠,切除左侧肾脏后1周,随机等分并制作为对照组、模型组和波生坦组,其中波生坦组给予波生坦100 mg/kg·d灌胃,每周各测血压1次,4周末处死动物,采静脉血放免法测定血浆ET-1浓度,取左心室行免疫组化检测内膜下心肌间微小动脉和毛细血管密度.结果血压4周末模型组和波生坦组分别为(180±8)mm Hg及(162±8)mm Hg,较对照组(122±5)mm Hg明显升高(P<0.05),而波生坦组则较模型组低(P<0.05);血浆中ET-1浓度模型组和波生坦组较对照组ET-1血浆浓度高(P<0.01),波生坦组较模型组高(P<0.01);微小动脉密度模型组(28.02±0.76)mm-2和波生坦组(23.64±0.82)mm-2分别比对照组(16.5±0.88) mm-2高,波生坦组较模型组低(P<0.01),而毛细血管密度模型组(1 823±110)mm-2和波生坦组(2 098±134)mm-2则分别比对照组(2 450±117)mm-2低,波生坦组较模型组高(P<0.01).结论波生坦能抑制DOCA-盐型高血压大鼠心内膜下微小动脉增多以及毛细血管稀疏化,ET-1在该模型的心脏微小血管重塑中可能发挥一定的作用.     

基质金属蛋白酶-2在高血压大鼠心脏中表达的意义及氨氯地平对其的影响

目的:探讨基质金属蛋白酶-2(MMP-2)在脱氧皮质酮-盐型高血压大鼠(DHR)心脏微小血管重塑中作用及其可能的调节机制。方法:30只雄性SD大鼠,切除左侧肾脏后1周,随机等分为3组。对照组,饮自来水;另2组分别为模型组和氨氯地平组,开始每周予脱氧皮质酮50 mg.kg-1,ip,连续5周;氨氯地平组用氨氯地平30 mg.kg-1.d-1灌胃,连续5周。5周末处死动物,按相应的要求留取血液和心脏标本,分别行血浆内皮素-1(ET-1)浓度、微小血管密度及MMP-2/MMP-2特异性组织抑制因子(TIMP-2)蛋白和基因表达的检测,评价在氨氯地平干预下微小血管病变与MMP-2/TIMP-2表达间关系。结果:在DHR左心室心内膜下心肌中存在微小动脉密度增加和毛细血管密度减少,MMP-2的mRNA和MMP-2/TIMP-2的蛋白表达上调;氨氯地平能抑制血压升高,明显减轻微小血管损害,下调MMP-2/TIMP-2的mRNA和蛋白表达。MMP-2的表达同微小血管密度间具有良好的相关性。结论:在DHR心脏中存在微小血管病变,MMP-2/TIMP-2表达可能参与微小血管病变的病理机制,血压可能是通过调节MMP-2/TIMP-2表达参与微小血管病变;干预MMP-2/TIMP-2的表达可能为防治高血压靶器官损害的新的靶点。     

盐酸埃他卡林对高血压肾脏损害的保护作用

目的研究盐酸埃他卡林(Ipt)对自发性高血压大鼠(SHR)肾脏损害的实验治疗学作用。方法将30只SHR分为Ipt1、3、9mg·kg-1·d-13个剂量组,贝那普利3mg·kg-1·d-1治疗组及SHR空白对照组,另设同月龄WKY大鼠为正常对照,灌胃给药每天1次,给药12周,观察其对大鼠的血压、心率、尿蛋白、肾组织病理改变以及血液和肾组织内皮素(ET-1)和转化生长因子(TGF)-β1影响。结果实验12周内,SHR对照组血压和心率进行性增高。Ipt3个剂量组均能有效降低SHR的血压,Ipt3、9mg·kg-1·d-1还可抑制SHR心率加快的趋势。而且Ipt1、3、9mg·kg-1·d-1均可减少尿蛋白排泄量,延缓肾小动脉的重塑,改善肾功能,降低SHR血液及肾组织ET-1和TGF-β1浓度的含量。但Ipt3、9mg·kg-1·d-1剂量组延缓SHR肾小动脉的重塑较1mg·kg-1·d-1剂量组明显。结论Ipt1、3、9mg·kg-1·d-1剂量组均在有效地控制SHR血压的同时,对SHR肾脏具有保护作用,此作用可能与其抑制血液及肾组织局部ET-1和TGF-β1水平有关。     

波生坦及氨氯地平对脱氧皮质酮-盐型高血压大鼠肾脏纤维化和微血管的影响

目的:比较波生坦和氨氯地平对脱氧皮质酮(DOCA)-盐型高血压大鼠(DHR)肾脏纤维化和微血管的影响,探讨内皮素-1(ET-1)在DHR肾脏损害中的作用及可能机制。方法:30只10周龄清洁级雄性SD大鼠,切除左侧肾脏,1周后存活24只,随机分成对照组、波生坦组、氨氯地平组和安慰剂组。对照组给予饮自来水,另3组予DOCA[50mg/(kg·周)]皮下注射,饮盐水,同时分别予波生坦、氨氯地平和安慰剂;5周时测定24h尿蛋白排泄量(24h-UPER)、血压、尿素氮(BUN)和血肌酐(Scr);处死后评估病理切片肾小球硬化和肾小管间质损害程度;观察转化生长因子β1(TGF-β1)和Smad7的表达,分析肾组织毛细血管指数和增生内皮细胞数。结果:与对照组相比,安慰剂组血压、24h-UPER增加,肾脏有较明显的组织学改变,肾内TGF-β1和Smad7的蛋白表达明显上调,波生坦能较显著地抑制上述异常(P0.05)。各组肾功能指标在正常范围内。安慰剂组中肾小球毛细血管指数(GCI)和肾小管周毛细血管指数(PCI)和增生内皮细胞数较对照组明显减少,波生坦、氨氯地平均能显著增加毛细血管和新生毛细血管数(P<0.01),但氨氯地平组增加程度不如波生坦组,差异有统计学意义(P<0.05)。TGF-β1与GCI、PCI和增生内皮细胞数具有显著的负相关性。结论:ET-1在DHR肾脏损害中发挥重要作用,其机制可能为通过上调TGF-β1和Smad7蛋白表达及直接抑制新生血管形成,间接加速毛细血管毁损而加重肾缺血和肾损害。     

女贞子、淫羊藿补肾中药对自发性高血压大鼠主动脉内皮舒缩功能的影响

目的 研究补肾中药女贞子、淫羊藿对自发性高血压大鼠(SHR)的血压、主动脉内皮舒张因子一氧化氮(NO)及收缩因子内皮素(ET-1)的影响,探讨补肾中药调节主动脉内皮舒缩功能的可能机制.方法 采用随机对照研究的方法将40只12~14周龄自发性高血压大鼠(SHR)随机分为女贞子组、淫羊藿组、阳性对照组、模型组,以同龄同种系正常血压的京都种大鼠(Wistar-Kyoto rat,WKY)10只作为正常组;女贞子组、淫羊藿组、阳性对照组分别给予女贞子、淫羊藿水煎液,依那普利水溶液,模型组和正常组给予蒸馏水灌胃.2 w后采用多导生理记录仪检测大鼠血压,处死大鼠后取腹主动脉血测定血清一氧化氮(NO),血浆内皮素-1(ET-1)的含量,取主动脉检测内皮eNOS、ET-1蛋白及eNOS mRNA、ET-1mRNA的表达.结果 用药后女贞子、淫羊藿使SHR大鼠的血压有所降低,但差异无统计学意义;女贞子组、淫羊藿组血液NO、主动脉内皮eNOS蛋白及eNOS mRNA表达较模型组升高(P<0.05),血液ET、主动脉内皮ET-1蛋白及ET-1 mRNA表达均明显降低(P<0.05).结论 单味中药女贞子、淫羊藿虽然没有明显降低血压,但略有下降的趋势,且能调节主动脉血管内皮舒缩因子.     

波生坦对大鼠颈动脉再狭窄的影响及其病理机制

目的 探讨波生坦对大鼠颈动脉再狭窄的影响及其病理机制.方法 选取Wistar大鼠65只,随机分为假手术组、损伤组及波生坦组.损伤组及波生坦组模拟临床经皮冠状动脉形成术(PTCA)过程行左颈总动脉球囊损伤致内膜剥落,波生坦组给予波生坦100 mg·kg-1·d-1灌胃(术前1 d直至处死).观测术后不同时相点的内膜,中膜动态增殖情况,并采用免疫组化法检测α-平滑肌肌动蛋白(α-SMA)和抗增殖细胞核抗原(PCNA).结果 损伤组术后28 d新生内膜增生达峰值,波生坦组术后14 d内膜增生达峰值.术后14、28、45 d波生坦组内膜面积较损伤组明显减小(P<0.001).术后14 d的波生坦组内膜PCNA的阳性率与损伤组比较显著降低(P<0.01).术后14 d α-actin的阳性表达率较损伤组明显增加(P<0.01).结论 波生坦组可通过抑制血管内膜过度增殖及减少血管平滑肌细胞的增殖,转型和迁移而有效预防PTCA术后再狭窄的发生.     

阿托伐他汀对自发性高血压大鼠主动脉活性氧、AT1受体和p22phox表达的影响

目的探讨自发性高血压大鼠(SHR)主动脉活性氧(ROS)、AT1受体和p22phox mRNA表达的相关性及阿托伐他汀治疗对其影响.方法以正常血压大鼠为对照,观察SHR给予阿托伐他汀50 mg*kg-1*d-1灌胃30 d后,血压、血浆血管紧张素Ⅱ(AngⅡ)、血清一氧化氮(NO)、主动脉ROS含量、AT1受体蛋白和mRNA以及p22phox mRNA表达的变化.结果阿托伐他汀治疗30 d后,SHR血压、血浆AngⅡ、主动脉ROS含量、AT1受体蛋白和mRNA及p22phox mRNA表达下降,血清NO水平上升.多元逐步回归分析显示AT1受体为血管ROS的主要影响因素.结论血管AT1受体mRNA表达增加引起p22phox亚单位表达上调,导致ROS合成增加是高血压血管ROS增多的重要机制.阿托伐他汀可下调血管AT1受体和p22phox亚单位表达,减少ROS,减轻血管内皮功能受损.     

生芪降糖颗粒对2型糖尿病大鼠血糖、血脂及血管内皮素表达的影响

目的 探讨生芪降糖颗粒对糖尿病大鼠血糖、血脂及血管内皮素表达的影响.方法 制作2型糖尿病大鼠模型,随机分为生芪降糖颗粒低剂量组、中剂量组、高剂量组、文迪雅组、对照组.正常组给予蒸馏水灌胃,模型组分别给予生芪降糖颗粒低剂量、中剂量、高剂量、文迪雅、蒸馏水灌胃,至血糖下降至正常组水平或与造模时比较有统计学差异为治疗有效.测定各组血糖、总胆固醇(TC)、甘油三酯(TG)、胰岛素、主动脉内皮素1(ET-1)的变化及ET-1mRNA表达.结果 药物干预后生芪降糖颗粒中、高剂量组和文迪雅组血糖、TC、TG和胰岛素明显下降(P均<0.01).文迪雅组和生芪降糖颗粒高剂量组ET-1和主动脉El-1mRNA表达量较对照组均显著下降(P均<0.01).结论 ①生芪降糖颗粒有抗糖尿病作用,并呈剂量依赖性;②生芪降糖颗粒降低ET-1mRNA的表达,可保护和改善糖尿病大鼠主动脉内皮和心肌的功能.     

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.