褪黑素水平对抑郁症患者下丘脑-垂体-肾上腺轴功能的影响

目的探讨抑郁症患者褪黑素(MT)水平对下丘脑-垂体-肾上腺轴(HPA)功能的影响。方法对86例抑郁症患者,检测血清MT、促肾上腺皮质激素释放激素(CRH)、促肾上腺皮质激素(ACTH)、皮质醇(COR),并分析其相互关系。结果1以MT中位数(51.3ng/L)为切点,将所有抑郁症患者分为MT高值组(51.3ng/L,n=43)与MT低值组(51.3ng/L,n=43),前者血清CRH、ACTH、COR均显著低于后者(t=3.330,3.315,2.314;P0.01,0.01,0.05);2血清MT水平与CRH、ACTH水平负相关(r=-0.414,-0.329;P0.01,0.05)。结论褪黑素对抑郁症患者的HPA轴功能可能有一定的抑制作用。     

褪黑素对大鼠下丘脑-垂体-肾上腺轴及免疫功能受抑状态的影响

目的 :探讨外源性褪黑素对下丘脑 垂体 肾上腺轴及免疫功能受抑状态的影响。方法 :采用放射免疫法及细胞免疫技术分别观察了两个不同剂量 (10 0、2 0 0 μg kg)褪黑素连续 14天腹腔注射 ,对皮质酮诱导的HPA轴及免疫功能受抑大鼠血浆ACTH ,皮质酮水平以及淋巴细胞增殖 ,NKCC杀伤活性和ConA诱生的IL 2水平的影响。结果 :褪黑素 10 0 μg kg处理动物 ,其明显下降的血浆ACTH及皮质酮水平均有上升趋势 ,但在统计学上无显著意义 ,而褪黑素 2 0 0 μg kg处理动物 ,其血浆ACTH及皮质酮水平的上升与皮质酮对照组相比有显著意义 (P <0 0 5 )。对免疫功能的影响 ,无论褪黑素 10 0 μg kg还是 2 0 0μg kg处理动物 ,其被抑制的细胞免疫功能 (淋巴细胞增殖、NKCC及IL 2水平 )均有所恢复 ,且与皮质酮对照组相比 ,差异显著(P <0 0 5 )。结论 :外源性褪黑素可改善皮质酮诱导的大鼠HPA轴及免疫功能受抑状态。     

松果体褪黑素与下丘脑-垂体-肾上腺轴的相互作用

近年来很多学者发现松果体褪黑素(MLT)可以通过下丘脑垂体肾上腺轴(HPA)影响机体免疫功能,本文主要列举了松果体MLT对HPA轴三个水平调节的新发现和可能的机制,证实松果体MLT对垂体和肾上腺皮质有明显的调节作用,但对下丘脑是否有调节作用还存在诸多争议,同时也简述了HPA轴对松果体MLT影响研究的新进展,提示二者实际上存在着昏综复杂的相互作用。     

褪黑素对创伤后应激障碍大鼠下丘脑-垂体-肾上腺轴的影响

目的:探讨褪黑素(MLT)对足部电击所致创伤后应激障碍(PTSD)大鼠下丘脑-垂体-肾上腺(HPA)轴的影响。方法:利用足底电击法制备大鼠PTSD模型,通过腹腔注射方法给予治疗组大鼠MLT。通过拒俘反应测试检测大鼠的行为学变化,利用real time RT-PCR方法检测下丘脑中促肾上腺皮质激素释放激素(CRH)mRNA的表达,利用酶联免疫吸附试验(ELISA)检测血清中促肾上腺皮质激素(ACTH)、肾上腺素(EPI)和糖皮质激素(GC)的含量。结果:PTSD组大鼠拒俘反应明显(P<0.05),下丘脑中CRH mRNA表达升高(P<0.05),血清中ACTH和EPI明显升高(P<0.05),但是GC水平下降(P<0.05)。MLT治疗后可以明显缓解PTSD大鼠拒俘反应(P<0.05),同时降低下丘脑中CRH mRNA表达(P<0.05),降低血清中ACTH和EPI水平并升高GC的水平(P<0.05)。结论:MLT治疗可缓解PTSD大鼠的症状,并恢复HPA轴的神经内分泌平衡。     

下丘脑-垂体-肾上腺轴与糖尿病

1型和2型糖尿病患者表现为糖皮质激素分泌过多和下丘脑-垂体-肾上腺轴(HPA轴)功能改变。糖尿病HPA轴功能障碍在中枢和外周水平都有发生,且与长期慢性应激、胰岛素抵抗等相关,另外一些脂肪细胞产物及调节因子也可能参与其中。HPA轴功能异常可能促使糖尿病发生,但也可能是糖尿病造成的后果,不管因果如何糖皮质激素的增加对糖尿病控制是不利的。     

中国劲酒对肾阳虚模型大鼠下丘脑-垂体-肾上腺轴及免疫功能的影响

目的:研究中国劲酒对皮质酮致肾阳虚模型的大鼠下丘脑-垂体-肾上腺(Hypothalamic-pituitary adrenal,HPA)轴及免疫功能的影响。方法:取健康清洁级雄性SD大鼠45只,按随机数字表法分为空白对照组、模型组和中国劲酒组,每组15只,通过皮下注射外源性皮质酮(10 mg/kg体重)连续14天抑制HPA轴,制备肾阳虚模型。皮质酮注射前5天,以50 ml/kg体重灌胃中国劲酒(相当于中国劲酒日推荐服用剂量的30倍),连续19天。采用酶联免疫吸附试验(ELISA)方法检测血浆皮质酮(Corticosterone,CORT)含量;采用放射性免疫法测定血浆中促肾上腺皮质激素(Adrenocorticotropic hormore,ACTH)含量,采用实时定量-聚合酶链反应法(Real-time PCR)测定下丘脑促肾上腺皮质激素释放激素(Corticotropin releasing hormone,CRH)mRNA表达水平;取胸腺称重,淋巴细胞凋亡及增殖率分别采用流式细胞仪法和改良四氮唑盐(XTT)法。结果:在外源性皮质酮作用下,肾阳虚模型大鼠较空白对照组HPA轴和免疫功能受到明显抑制,中国劲酒灌胃后可显著提高大鼠下丘脑CRH mRNA水平、血浆ACTH含量,与肾阳虚模型组比较差异有统计学意义(P<0.05);血浆CORT水平有升高倾向;同时在免疫调节方面,中国劲酒可明显增加皮质酮模型大鼠胸腺重量和降低脾脏淋巴细胞凋亡率,与肾阳虚模型组比较差异有统计学意义(P<0.01);中国劲酒有促进淋巴细胞增殖的趋势。结论:中国劲酒能改善肾阳虚模型大鼠HPA轴功能;也具有改善肾阳虚模型大鼠免疫功能的作用。     

外源性糖皮质激素对大鼠下丘脑—垂体—肾上腺—胸腺轴的影响

本文观察大鼠每在皮下注射皮质酮（１～５０ｍｇ／ｋｇ，连续１４天）后下丘脑－垂体－肾上腺－胸腺（ＨＰＡＴ）轴的形态与机能改变，结果表明：实验大鼠垂体，肾上腺，胸腺重量减轻，下丘脑单胺类递质含量升高，下丘脑室旁核促肾上腺皮质素释放因子（ＣＲＦ）分泌细胞及正中隆起ＣＲＦ神经纤维和垂体前叶促肾上腺皮质激素（ＡＣＴＨ）分泌细胞等数量减少，染色变淡，血浆皮质酮（ＣＯＲＴ）和ＡＣＴＨ浓度降低。淋巴细胞增殖反应及     

脑缺血再灌注对大鼠下丘脑-垂体-肾上腺-胸腺轴的影响

为探讨脑缺血再灌注损伤对大鼠神经-内分泌和免疫功能的影响,本研究采用免疫组织化学和放射免疫等实验技术,从形态、结构和功能三个层次观察了脑缺血再灌注损伤时大鼠下丘脑-垂体-肾上腺-胸腺(HPAT)轴的变化。结果发现:脑缺血后6h、9h组大鼠垂体重量明显减轻;其下丘脑和垂体激素分泌细胞数量减少,体积缩小;脑缺血后血浆CRH、ACTH和CORT浓度呈一致性先短暂升高后持续下降,T细胞增殖能力、T细胞克隆形成率和IL-2活性明显下降,且上述改变缺血9h组重于6h组。当脑缺血恢复再灌注时,缺血3h再灌注组比缺血6h再灌注组恢复快。以上结果表明:①脑缺血再灌注时,HPAT轴先出现一短暂的激活过程,继而很快转入抑制状态;②脑缺血再灌注损伤后大鼠免疫功能受抑制;③缺血后恢复再灌注早,HPAT轴受损轻,恢复快。     

重组白细胞介素-2对小鼠下丘脑-垂体-肾上腺轴的影响

目的：研究重组白细胞介素２（ｒＩＬ－ ２） 对下丘脑－ 垂体－ 肾上腺轴的作用。方法：采用ｒＩＬ－ ２ 静脉注入（Ｂ组注入前用抗－ ＣＲＨ 血清预处理） ,测定注入ｒＩＬ－ ２ 后不同时间ＣＲＨ,ＡＣＴＨ 及ＣＯＲＴ 血浆含量变化。结果：ｒＩＬ－ ２ 可使不同水平的ＣＲＨ,ＡＣＴＨ,ＣＯＲＴ 血浆含量升高（Ａ 组）（ Ｐ＜ ０－０１） ,当预先注入抗－ ＣＲＨ 血清后ＡＣＴＨ、ＣＯＲＴ 的升高不被阻断（Ｂ 组） 。结论：ｒＩＬ－ ２ 对ＨＰＡＡ 的激活作用不是通过ＣＲＨ 介导的     

下丘脑-垂体-肾上腺轴在抑郁症发病中的作用

越来越多的研究表明，下丘脑一垂体一肾上腺轴(hypothalamic pituitary adrenal axic，HPA轴)在抑郁的发病机制中发挥着重要的作用。HPA轴的活化机制是：下丘脑通过垂体门脉系统运送下丘脑调节肽(促肾上腺皮质激素释放激素，CRH)到脑垂体，从而调节腺垂体的分泌。腺垂体在调节肽的作用下释放促肾上腺皮质激素(ACTH)，然后作用于肾上腺皮质，释放肾上腺皮质激素到全身。下面我们将从HPA轴的三个水平(CRH、ACTH、肾上腺皮质激素)来论述HPA轴在抑郁发病过程中的作用。     

糖尿病大鼠味腺超微结构的研究

目的观察2型糖尿病大鼠味腺超微结构变化。方法雄性Wistar大鼠18只,随机分为对照组和实验组,高脂喂养加小剂量链脲佐菌素(STZ)腹腔注射制备2型糖尿病模型,饲养8周后取轮廓乳头,应用透射电镜观察味腺超微结构。结果与对照组大鼠比较,实验组大鼠味腺腺泡细胞的核膜凹陷、核固缩;线粒体嵴断裂、空泡变性;粗面内质网扩张,脱颗粒。结论糖尿病可导致味腺组织出现一系列超微结构病理改变,为进一步探讨糖尿病发生机制提供了形态学依据。     

低氧预适应对移植大鼠肝细胞线粒体超微结构的影响

目的 观察低氧预适应(HP)对移植大鼠肝细胞线粒体超微结构的影响. 方法 采用改良的自体肝移植模型模拟肝移植过程,将72只SD大鼠随机分为正常对照(NC)、自体移植(AT)和低氧预适应(HP)3个组,每组24只.HP为术前用8%氮氧混合气体处理90min,分别于术后1、6、24h处死大鼠取肝脏标本,透射电镜观察肝细胞及线粒体的形态学改变,并用图像分析系统定量评判线粒体超微结构的改变程度. 结果 透射电镜下见AT组线粒体肿胀明显,膜模糊不清,部分膜破裂,线粒体嵴疏松溶解,有空泡形成;而HP组线粒体结构基本正常,仅有轻度肿胀,线粒体排列整齐,膜基本完整,线粒体嵴密集,未见空泡形成;定量分析线粒体的面积、周长及直径均和AT组有显著性差异(P<0.05),HP组线粒体损伤程度较AT组有明显改善. 结论 线粒体超微结构的改变是移植后肝细胞损伤的早期变化,HP可改善这一变化以减轻肝细胞损伤.     

ANTI-GLUCOCORTICOID EFFECTS OF MELATONIN ON ADULT RATS

To extend our previous experiment on anti-glucocortlcoid effects of melatonin which was performed under a very special condition using young rats, we have carried out another experiment of long term administration of pineal hormone melatonin to adult female rats which were conditioned by overdose glucocorticoid. The results clearly demonstrated significant protection, by melatonin, from the injurious effects of a glucocorticoid, dexameth-asone: decrease of body weight gain, atrophy of the thymus and adrenals, and elevation of the level of total cholesterol in blood. Thus, it has been clarified that anti-glucocorticoid effects of melatonin could be shown experimentally not only in young rats but also in adults, and also, could be really seen not only in short term experiment but also in longer ones. Anti-glucocorticoid effects of melatonin seem to be of considerably wide range, not being limited to occur under a special condition, including the age of animals, in experiments.     

ANTI-GLUCOCORTICOID EFFECTS OF MELATONIN IN YOUNG RATS

Administration of the pineal hormone melatonin to young female rats provided significant prevention of the injurious effects (decrease of body weight gain, atrophy of the thymus and adrenals, glucosuria, elevation of the blood level of glucose, free fatty acid, triglyceride, and total cholesterol) caused by three different glucocorticoids, i.e. dexamethasone, prednisolone, and hydrocortisone. Although these protective effects of melatonin were slightly more remarkable in dexamethasone-treated rats than in prednisolone- or hydrocortisone-treated rats, our hypothesis of melatonin's anti-glucocorticoid effects is said to have been confirmed rather universally and with a considerably wide range through this experiment.     

褪黑素受体亚型Mel 1a和Mel 1b在大鼠中枢神经系统的分布差异--原位杂交研究

目的 研究Mel 1a、Mel 1b褪黑素膜受体在大鼠中枢神经系统的表达及分布差异。方法 原位杂交组织化学。结果 (1)Mel 1a mRNA阳性细胞主要分布于海马、大脑皮层、视上核、室旁核、视交叉上核、橄榄核、小脑皮层、小脑顶核、脊髓前角、面神经核、巨细胞网状核、纹状皮质、三叉神经核等。(2)Mel 1b mRNA阳性细胞主要分布于小脑皮层和顶核、球状核、栓状核、海马、大脑皮层、脊髓前角、视上核和交叉上核。结论 Mel 1a mRNA在中枢分布广泛、含量丰富，而Mel 1b mRNA在中枢分布较局限。在海马和大脑皮层，这两种受体均有丰富表达。     

THE EFFECTS OF MELATONIN ON HUMORAL IMMUNE RESPONSES OF YOUNG AND AGED RATS

The pineal gland with its effects on immune system and free radicals may have a role on aging process. In this study, we investigated the effects of melatonin (10 mg/kg/d, s.c. for 7 days), the main secretion of the pineal gland, on the humoral immune responses of aged and young male Wistar rats. Eighteen aged (28 months old; 6 in control group and 12 in melatonin group) and 25 young (9 months old; 10 in control group and 15 in melatonin group) rats were given 4×10⁸ sheep erythrocytes i.p. in order to evoke humoral immune responses. After a booster injection at the end of a period of three-weeks following the last melatonin injection, IgM and IgG1 levels were measured. Melatonin was found to increase IgG1 and IgM responses of aged rats when compared to controls (p=0.049 and p=0.007), respectively. In the young rats, while the IgG1 levels of control group were significantly higher than that of the melatonin group (p=0.021), IgM levels were not significantly different (p=0.563). It is concluded that exogenous melatonin may augment the depressed humoral immune responses seen aged rats.     

THE EFFECTS OF MELATONIN ON HUMORAL IMMUNE RESPONSES OF YOUNG AND AGED RATS

The pineal gland with its effects on immune system and free radicals may have a role on aging process. In this study, we investigated the effects of melatonin (10 mg/kg/d, s.c. for 7 days), the main secretion of the pineal gland, on the humoral immune responses of aged and young male Wistar rats. Eighteen aged (28 months old; 6 in control group and 12 in melatonin group) and 25 young (9 months old; 10 in control group and 15 in melatonin group) rats were given 4×10⁸ sheep erythrocytes i.p. in order to evoke humoral immune responses. After a booster injection at the end of a period of three-weeks following the last melatonin injection, IgM and IgG1 levels were measured. Melatonin was found to increase IgG1 and IgM responses of aged rats when compared to controls (p=0.049 and p=0.007), respectively. In the young rats, while the IgG1 levels of control group were significantly higher than that of the melatonin group (p=0.021), IgM levels were not significantly different (p=0.563). It is concluded that exogenous melatonin may augment the depressed humoral immune responses seen aged rats.