两种调脂药物对高脂血症性脂肪肝治疗的实验性研究.

目的探讨不同作用机制的调脂药(非诺贝特和辛伐他汀)对高脂血症性脂肪肝的作用.方法高脂食饵性喂养诱导大鼠高脂血症性脂肪肝模型.分别给予非诺贝特、辛伐他汀治疗,观察肝指数、肝功能,血脂、肝脂、血清及肝组织过氧化脂质(MDA)含量及组织学的变化.结果非诺贝特显著降低血脂,分别为TC(mmol/L)1.80±0.20与2 10±0.33,TG(mmol/L)0.76±0.18与1.09±0.31、血清及肝组织MDA含量(nmol/ml)分别3.97±0.57与6.89±1.22和75.22±20.88与106.69±15.60,但ALT、ALP、肝脂、肝指数却显著升高,肝组织学呈重度脂肪变;辛伐他汀显著降低血脂、肝脂、血清及肝组织MDA含量,对肝功能无影响,肝组织学接近正常.结论非诺贝特虽可显著降低血脂,但却加重肝内脂质沉积,不宜用于高脂血症性脂肪肝的治疗.辛伐他汀显著降低血脂及肝脂,降低脂质过氧化,,对肝功能无影响,可较安全、有效地用于高脂血症脂肪肝的治疗.     

降脂理肝汤对非酒精性脂肪肝大鼠生化指标的影响

目的:观察降脂理肝汤对非酒精性脂肪肝大鼠血脂、肝脂质、丙二醛(malondialdehyde,MDA)、超氧化物歧化酶(superoxide dismutase,SOD)、肿瘤坏死因子(tumor necrosis factor-α,TNF-α)等生化指标的影响.方法:通过高脂饮食诱导非酒精性大鼠脂肪肝模型,随机分为正常组、模型组、甘乐组(复方二氯醋酸二异丙胺5.5 mg/kg)、降脂理肝汤高、中、低剂量组(9.2、4.6、2.3 g生药/kg),16 wk后取材,检测肝功能、血脂、肝脂质、MDA、SOD、TNF-α.结果:与模型组比较,降脂理肝汤组均可显著降低血清低密度脂蛋白(low-density lipoprotein,LDL)、游离脂肪酸(free fatty acids,FFA)、甘油三酯(triglyceride,TG)、MDA水平(P0.01或P0.05)和丙氨酸氨基转移酶(alanine transaminase,ALT)活性(P0.05或P0.01),高剂量组显著降低TNF-α水平(P0.01),提高SOD活性(P0.01);所有给药组均可改善肝脏脂肪变性程度,其中高剂量组效果明显.结论:降脂理肝汤可通过调节脂代谢,改善脂质过氧化,降低血清TNF-α含量治疗非酒精性脂肪肝.     

非诺贝特治疗酒精性与药物性脂肪肝的实验研究

目的 研究非诺贝特对酒精性脂肪肝以及药物性脂肪肝的作用,并探讨两种脂肪肝的发病机制。方法 建立酒精性脂肪肝和药物性脂肪肝大鼠模型并分为治疗组(80 mg/kg)和对照组。4周后处死,分别测定肝功能,血清甘油三酯(TG)、胆固醇(TC)、高密度脂酯(HDL),血清及肝组织丙二醛(MDA)、肝脂酯(HL),脂蛋白脂酶(LPL)及肝脏病理变化。 结果 酒精性脂肪肝非诺贝特组与对照组比较,血清TG治疗组为(1.07±0.06)mmol/L,对照组为(1.56±0.29)mmol/L,血清MDA分别为(1.10±0.22)nmol/L和(1.26±0.21)nmol/L,肝组织内MDA分别为(5.92±1.24)nmol/g和(7.42±1.22)nmol/g,血清内HL分别为(0.053±0.006)μEq·ml-1·h-1和(0.037±0.006)μEq·ml-1·h-1,LPL水平明显升高分别为(0.018±0.004)μEq·ml-1·h-1和(0.014±0.004)μEq·ml-1·h-1;肝组织HL分别为(0.075±0.010)μEq·ml-1·h-1和(0.065±0.007)μEq·ml-1·h-1,LPL分别为(0.022±0.014)μEq·ml-1·h-1和(0.008±0.002)μEq·ml-1·h-1,TC的水平无明显变化,肝内脂质含量分别为(26.01±1.69)mg/g和(71.45±2.66)mg/g,同时肝脏病理明显改善。药物性脂肪肝非诺贝特组与对照组比较肝脏病理改变差异无显著意义。 结论 非诺贝特治疗酒精性脂肪肝可以明显减少肝内脂质的含量,改     

甜菜碱对大鼠酒精性脂肪肝的影响

目的研究甜菜碱对大鼠酒精性脂肪肝的影响.方法制备酒精性脂肪肝大鼠动物模型,用甜菜碱0.2～0.8g/kg干预,6周后观察血清脂质、肝功能生化指标和脂质过氧化指标的变化,并观察肝组织学改变.结果酒精性脂肪肝大鼠给予甜菜碱0.2～0.8 g/kg治疗6周后,可剂量依赖性地降低血清总胆固醇、三酰甘油、低密度脂蛋白-胆固醇、游离脂肪酸水平和增加高密度脂蛋白-胆固醇含量(P＜0.05或P＜0.01),也能剂量依赖性地降低肝重系数、肝脂质和丙二醛含量(P＜0.05或P＜0.01),较大剂量(0.8g/kg)时还可升高肝组织中超氧化物歧化酶含量(P＜0.01).病理检查结果显示给予甜菜碱后可使肝细胞的脂肪变性程度明显减轻(P＜0.05或P＜0.01).结论甜菜碱对大鼠酒精性脂肪肝有较好的治疗作用,其部分机制可能是通过抗脂质过氧化和增加脂质代谢.     

实验性兔脂肪肝肝脂酶活性变化及茶多酚的作用

目的 观察肝组织中肝脂酶(HL)活性变化与肝细胞脂肪变性的关系,探讨茶多酚对HL活性变化的影响及机制。 方法 雄性新西兰白兔分为三组:脂肪肝组6只喂高脂饲料;茶多酚组7只喂高脂饲料,同时口服茶多酚200μg·g-1·d-1;正常对照组6只喂普通兔饲料。实验8周后测定血脂水平、血浆HL活性水平,肝组织做病理形态学检查同时用吐温法行HL活性染色,用硫代巴比妥酸比色法测定肝组织丙二醛(MDA)含量。 结果 脂肪肝组均产生重度混合型脂肪肝,血总胆固醇(TC)为(28.49±5.99)mmol/L,正常对照组为(1.11±0.82)mmol/L,t=21.654,P<0.05;血清低密度脂蛋白胆固醇(LDL-c)为(12.15±1.95)mmol/L,正常对照组为(0.71±1.14)mmol/L,t=12.400,P<0.05;肝组织MDA含量为(75.58±29.88)nmol/mg,正常对照组为(43.64±16.95)nmol/mg,t-2.278,P<0.05。每100μm2肝组织中HL活性点个数为1.76±0.10,正常对照组为4.14±0.05,t=3.306,P<0.05。茶多酚组:肝脏病理改变5只兔为中度混合型脂肪肝,2只兔为轻度混合型脂肪肝,明显轻于脂肪肝组。血TC为(16.87±6.58)mmol/L,明显低于脂肪肝组高于正常对照组(t值分别为5.786和3.968,P<0.05)。血LDL-c为(5.10±4.19)mmol/L,明显低于脂肪肝组(t=2.478,P<0.05)高于正常对照组(t=3.7634,P<0.05)。肝组织MDA含     

蒙药德都红花-7味散对高脂饮食诱导实验性脂肪肝大鼠血脂四项和SOD、MDA的影响

目的:观察蒙药德都红花-7味散对非酒精性脂肪肝的治疗作用及其机制,为临床用药提供理论依据.方法:取Wister♂大鼠,随机分为空白组8只、空白给药(德都红花-7味散)、模型组、德都红花-7味散低、高剂量组,各组10只.除空白组和空白给药组,按2 m L/100 g脂肪乳剂灌胃,1次/d,共计给脂肪乳剂灌胃4 wk.空白给药组、德都红花-7味散低、高剂量组分别给予蒙药德都红花-7味散0.6、0.6、3.0 g/(kg·d).各给药组均提前7 d给药,给药体积为1 m L/100 g,1次/d,灌胃给药;其他两组灌胃等体积蒸馏水,共计给药5 wk.观察各组大鼠血脂四项,肝功,肝组织匀浆中总胆固醇(cholesterol,CHO)、甘油三酯(triglyceride,TG)、超氧化物歧化酶(superoxide dismutase,SOD)、丙二醛(malondialdehyde,MDA)含量;HE染色观察肝脏细胞脂肪变程度.结果:与空白组比较,模型组大鼠血清TG、CHO、低密度脂蛋白(low density lipoprotein cholesterol,LDL-C)、肝匀浆TG、CHO、MDA、空白给药组MDA升高,血清高密度脂蛋白(high density lipoprotein cholesterol,HDL-C)、肝匀浆SOD明显降低;德都红花-7味散低、高剂量组大鼠血清CHO、LDL-C升高,有显著性差异(P0.05).与模型组比较,低剂量组血清TG降低,高剂量组血清CHO、LDL-C降低、HDL-C升高,空白给药组肝匀浆TG、CHO、MDA降低,SOD升高;低剂量组肝匀浆TG、CHO、MDA降低,高剂量组肝匀浆TG、MDA降低,SOD升高有显著性差异(P0.05).给药组肝组织脂肪变程度较模型组明显减轻.结论:蒙药德都红花-7味散治疗高质饮食脂肪肝疗效确切,抗脂质过氧化可能是其治疗机制的一部分.     

复方甘正对非酒精性脂肪肝的治疗作用

[目的]观察复方甘正对高脂饮食诱导的大鼠非酒精性脂肪肝(NASH)的治疗作用。[方法]将30只SD大鼠随机分为3组:正常组、模型组和复方甘正治疗组。测定各组空腹血清丙氨酸氨基转移酶(ALT)、天冬氨酸转氨酶(AST)、总胆固醇(TC)、三酰甘油(TG)及肝匀浆TG、TC的水平,同时检测肝匀浆丙二醛(MDA)水平及超氧化物歧化酶(SOD)活性。[结果]模型组体重(493.20±19.55)g比正常组(371.60±31.69)g显著增高(P<0.01),治疗组(421.80±15.51)g较模型组显著降低(P<0.05)。模型组肝指数(3.33±0.74)比正常组(2.89±0.14)显著增高,治疗组(2.97±0.10)较模型组显著降低(均P<0.05);正常组肝细胞无脂肪变性,模型组普遍发生脂肪变性,治疗组肝脂肪变性程度较模型组显著减轻,正常组无炎性细胞浸润,模型组肝小叶内出现汇管区炎症,炎症活动度明显高于正常组,治疗组较模型组明显减低(均P<0.01);模型组血清ALT、AST及TC较正常组均显著升高,治疗组较模型组显著下降,但仍高于正常组(P<0.01,<0.05)。模型组血清TG水平与正常组接近,治疗组与模型组比较下降不明显;模型组肝匀浆TG、MDA水平高于正常组,SOD活性低于正常组;治疗组TG、MDA较模型组显著下降(均P<0.01),TG已降至正常水平。治疗组SOD活性较模型组明显增加,但低于正常组(均P<0.01),3组间TC水平比较差异无统计学意义。[结论]复方甘正具有显著的抗炎、抗脂质过氧化和清除氧自由基的作用。     

褪黑素对非酒精性脂肪性肝炎大鼠肝脏CYP2E1表达的影响

目的 观察褪黑素(melatonin,MT)对非酒精性脂肪性肝炎大鼠肝脏CYP2E1表达的影响.方法 雄性Wistar大鼠50只,随机分成5组,每组10只,正常对照组予普通饲料,模型组、MT低剂量组、MT中剂量组、MT高剂量组予高脂饮食12周,各MT干预组依次给予MT(含≤1%无水乙醇)2.5 mg·kg-1·d-1、5.0 mg·kg-1·d-1、10 mg·kg-1·d-1腹腔注射,正常对照组、模型组予等量生理盐水(含1%无水乙醇)腹腔注射,12周末进行肝脏病理学检查.生化法测定肝匀浆三酰甘油(TG)、总胆同醇(TC)、超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱苷肽过氧化物酶(GSH-Px)值,免疫组化法检测肝脏CYP2EI的表达.结果 与正常对照组比较,模型组大鼠肝细胞呈中-重度脂肪变性,肝匀浆TG、TC、MDA值明显升高(P＜0.01);肝匀浆SOD、GSH-Px明显降低,CYP2F1表达强度增加.与模型组比较,各MT干预组肝脏病理变化逐渐改善,肝匀浆TC、TG、MDA值逐渐降低,肝匀浆SOD、GSH-Px活力则逐渐升高,MT高剂量组肝脏CYP2E1表达减弱(P＜0.05).结论 MT能显著抑制非酒精性脂肪性肝炎大鼠肝脏CYP2E1的表达,提高抗氧化酶活性,抑制脂质过氧化反应.     

葛根素对实验性脑出血大鼠脑组织SOD、MDA水平变化和神经功能障碍的相关性研究

目的:探讨葛根素对脑出血的治疗作用及其作用机制。方法:采用立体定向胶原酶尾状核注射法制备动物模型。观察脑出血大鼠神经功能障碍程度,检测大鼠脑组织超氧化物歧化酶(SOD)活性和脂质过氧化产物丙二醛(MDA)含量的变化。结果:与模型组比较,葛根素组的偏瘫症状明显减轻,脑组织MDA含量明显降低[(54.80±6.72)nmol/g比(70.22+8.24)nmol/g](P<0.01),而SOD活性显著提高[(2.32±0.09)kNU/g比(1.29±0.07)kNU/g](P<0.01)。结论:葛根素对脑出血后神经功能损伤有保护作用。其机制可能与葛根素具有减少自由基的产生,加强机体对自由基的清除能力和增强机体抗脂质过氧化损伤能力有关。     

苍菊清肝降脂方对脂肪肝大鼠肝组织脂肪沉积、氧化应激和脂质过氧化的影响

[目的]:研究苍菊清肝降脂方对脂肪肝大鼠肝组织脂肪沉积、氧化应激和脂质过氧化的影响。[方法]采用雄性Wistar大鼠予以CCl4联合高脂低蛋白饮食复制脂肪肝模型,大鼠随机分成正常组、模型组和中药干预组。实验结束处死大鼠,肝组织行油红O染色,并检测肝组织甘油三酯、SOD、GSH和MDA等指标。[结果]油红O染色发现中药干预组肝细胞脂肪变性明显减轻,尤其以大剂量组减轻程度更为明显,同时大鼠肝组织中TG含量较模型组均显著下降(小剂量组P<0.05,大剂量组P<0.01),大剂量组降低程度显著优于小剂量组(大剂量组与小剂量组比较P<0.05)。大鼠肝组织中SOD活性和GSH含量较模型组均明显升高,MDA含量则显著下降(小剂量组P<0.05,大剂量组P<0.01);大剂量组对SOD活力和MDA含量的改善程度显著优于小剂量组(大剂量组与小剂量组比较P<0.05),但大剂量组和小剂量组GSH含量差异无统计学意义(P>0.05)。[结论]苍菊清肝降脂方显著降低脂肪肝大鼠肝组织脂肪沉积,并能显著改善氧化应激和脂质过氧化的作用。     

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.