急性脑梗死HPA轴激素与胰腺内分泌变化的研究

目的:研究急性脑梗死(ACI)下丘脑-垂体-肾上腺(HPA)轴激素与胰腺内分泌的变化,以探讨其发病机理.方法:采用放射免疫分析法(RIA)分别对151例ACI患者进行CRH(促肾上腺皮质激素释放激素)、ACTH(促肾上腺皮质激素)、CS(皮质醇)、INS(胰岛素)及GLC(胰高血糖素)入院时始发状态血液检测,并与60例年龄相仿健康人组作对照.结果:ACI者HPA轴激素显著高于健康正常人组(P＜0.01～0.001),胰腺内分泌也发生了有重要统计学意义的变化(P＜0.05～0.001).结论:CRH、ACTH、CS、INS与GLC参与了ACI的病理发生发展过程,测定其水平可作为判断病情程度、愈后转归及疗效评定的客观指标.     

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     

地塞米松对哮喘大鼠肺组织ADM及基因表达的影响

目的： 探讨地塞米松(DEX)对哮喘大鼠肺组织肾上腺髓质素(ADM)及基因表达的影响。方法: 选择30只雄性SD大鼠随机分为3组，每组10只。采用卵蛋白皮下注射及雾化吸入制成大鼠哮喘模型；采用逆转录聚合酶链反应(RT-PCR)法检测各组肺组织ADM的mRNA表达水平，同时用免疫组化方法检测ADM表达水平，并在光镜下观察支气管壁厚度(WA/Pi)、支气管平滑肌厚度(平滑肌面积/Pi)及肺组织形态学改变。结果: 哮喘组(A组)ADM的mRNA和蛋白表达明显高于对照组(C组)(P<0.05)；治疗组（B组）ADM的mRNA和蛋白表达进一步增加，明显高于哮喘组(A组)(P<0.01)。结论: 地塞米松促进肺组织ADM表达升高，可能是其治疗哮喘的机制之一。     

HPA轴相关的帕金森病与骨质疏松症的共病机制研究进展

帕金森病 （Parkinson''s Disease,PD） 是骨质疏松症的独立风险因素。PD合并骨质疏松患者在临床上数量较多, 预后较差,给患者生活和公共卫生带来极大的负担。然而,目前依然缺乏对PD与骨质疏松共病机制的探索,为疾病的防治带来困难。下丘脑-垂体-肾上腺轴 （Hypothalamic-Pituitary-Adrenal axis,HPA） 活性异常在 PD患者中已有多年的研究,被认为参与了 PD 的发病机制。HPA 轴的激活与慢性压力相关,并且可以导致血浆皮质醇、糖皮质激素等固醇类激素水平上升。而慢性压力应激已被报道可以导致骨质流失,且糖皮质激素在临床上的应用也被认为与骨质疏松有关。这提示HPA轴的活性异常可能是PD共患骨质疏松症的重要机制。本综述针对PD患者中的HPA轴活性功能异常的病理过程,提出HPA轴活性异常可能通过导致固醇类激素水平异常上升、甲状旁腺激素水平异常以及交感神经系统异常三个方面影响骨代谢水平, 对PD和骨质疏松共患机制进行探索,以期为临床上PD患者的治疗提供线索和启示。     

安神解郁汤对CUMS大鼠海马p-Tau及HPA轴的影响

目的:观察安神解郁汤(ASJYD)对抑郁大鼠海马微管蛋白p-Tau及下丘脑-垂体-肾上腺(HPA)轴的影响。方法:雄性SD大鼠40只分为对照组(Control)、抑郁模型组(CUMS)和ASJYD治疗组(ASJYD),利用慢性不可预测轻度应激(CUMS)建立抑郁大鼠模型,通过灌胃方法给予抑郁大鼠ASJYD治疗;通过糖水偏好实验、旷场实验和Morris水迷宫测试各组大鼠的行为学表现; HE染色观察海马组织结构的变化;用Western Blot方法检测大鼠海马组织中p-Tau的表达水平; ELISA检测大鼠下丘脑促肾上腺皮质激素释放因子(CRF)和血清促肾上腺皮质激素(ACTH)变化。结果:糖水消耗和糖水偏好百分比模型组低于对照组和药物治疗组(P 0. 01)。旷场实验中行走路程、中央格时间、站立次数和修饰行为模型组低于对照组和药物治疗组(P 0. 01)。水迷宫平均逃避潜伏期模型组高于对照组和药物治疗组(P 0. 01)。HE染色各组海马组织结构发生显著变化。模型组大鼠海马p-Tau蛋白的表达低于对照组,用药治疗后显著提高(P 0. 01)。模型组下丘脑CRF含量和血清ACTH水平明显高于对照组,治疗后有明显改善(P 0. 01)。结论:安神解郁汤对CUMS大鼠抗抑郁作用,可调节p-Tau以及下丘脑CRF和血清ACTH的变化。     

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。     

大鼠肾脏机械损伤早期TNF-α及其受体的表达

探讨外源性ADM对肾脏机械性损伤早期TNF-α及受体表达的影响.选健康成年普通级Wistar大鼠104只.随机分为四组:对照组8只、创伤组32只、创伤前注射ADM组32只、创伤后注射ADM组32只,后三组的动物分别于创伤后1、6、12和24 h各处死8只.采用自由落体打击仪直接打击大鼠脊肋区制作肾机械性损伤模型.ADM分别于创伤前或创伤后10 min采用腹腔注射法给药.实验动物采用快速心脏采血法处死.取下肾脏标本,10%甲醛固定.观察TNF-α、TNFR在组织中的表达规律.结果表明:单纯创伤组于创伤早期TNF-α表达高于正常对照组,外源性ADM早期(1 h和6 h点)可抑制,TNF-α(P<0.05).单纯创伤组于创伤早期(1 h和6 h点)TNFR表达低于正常对照组,外源性ADM(创伤前给药)早期(1 h和6 h点)可上调节TNFR(P<0.05).说明TNF-α在创伤早期即参与了肾组织炎症的急性期反应并加重损伤.TNFR对TNF-α具有动态调节作用.ADM能降低TNF-α的分泌.ADM在早期肾损伤过程中可以上调TNFR,与其相互协调,共同发挥对损伤器官的保护作用.     

老年男性高血压患者血浆ADM和ET-1含量变化的意义

目的:探讨老年男性高血压患者血浆肾上腺髓质素(ADM)、内皮素-1(ET-1)含量变化的临床意义.方法:用放射免疫分析测定62例老年男性高血压患者血浆ADM、ET-1含量,并与35例年龄、性别匹配的健康老年人对照.结果:高血压组血浆ADM、ET-1含量显著高于正常对照组(P＜0.01),两者均随高血压分级1、2、3级组逐渐递增(P＜0.01,＜0.05);血压控制不良者明显高于血压控制良好者(P＜0.01),病情重组显著高于病情轻组(P＜0.01);伴肾功能受损者也显著高于肾功能正常者(P＜0.01);血浆ET-1含量平均增幅明显高于血浆ADM(P＜0.01);高血压组血浆ADM与ET-1含量呈正相关(r=0.394,P＜0.01);正常对照组两者含量不相关(r=0.172,P＞0.05).结论:老年男性高血压患者血浆舒血管活性肽ADM含量显著增高,可能是机体的一种代偿性自身调节机制,以此抑制ET-1等缩血管活性肽增高对血压调节产生不良的影响,对机体起到自身代偿性保护作用.     

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。     

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。     

Effects of early deprivation and maternal separation on pup-directed behavior and HPA axis measures in the juvenile female rat

Juvenile female rats show maternal-like behavior toward pups. The purpose of the following experiment was to investigate whether the HPA axis, through the use of early separation manipulations that alter HPA functioning in rats, plays a role in the juvenile response to foster pups. Female rats were early deprived or maternally separated for 5 hours daily from PND 2 to 14 and compared to animal facility-reared rats. Deprivation or separation increased CRH-R1 IR in the juvenile PVN, but had no other effects on other HPA measures or on maternal behavior. Pup-exposure during the juvenile period blunted corticosterone levels after acute and repeated pup-exposures when compared to exposure to novelty and conspecifics respectively. Repeated exposures to pups also increased CRH-R1 IR relative to isolation during the juvenile period. Overall, the data suggest that although pup-exposure affects corticosterone levels, the HPA axis does not relate to juvenile maternal behavior in the present experiments.     

Association between OPCRIT dimensions and polymorphisms of HPA axis genes in bipolar disorder

The aim of the study was to investigate the possible association between polymorphisms of HPA axis genes-CRHR₁ (corticotrophin-releasing hormone receptor), NR3C1 (glucocorticoid receptor) and AVPR1B (arginine vasopressin receptor) and dimensions of bipolar disorder assessed by OPCRIT.     

内皮素在急性肝衰竭时肾功能障碍发生中的作用

目的：探讨内皮素在急性肝衰竭时肾功能障碍发生中的作用。方法：对硫代乙酰胺（ＴＡＡ）诱导的急性肝衰竭大鼠肝肾功能及内皮素水平进行动态观察。结果：随着肝损伤的加重，肾功能亦进行性恶化（表现为血肌酐升高，肌酐清除率下降，尿量减少，尿钠分泌降低等），血浆内毒素逐渐升高，均于４８ｈ最为严重。伴随上述变化，肾组织内皮素活性渐升高，亦于４８ｈ达高峰。血浆内皮素和肌酐清除率及肌酐清除率与肾组织内皮素水平之间均呈显     

Circadian phase and sex effects on depressive/anxiety-like behaviors and HPA axis responses to acute stress

Circadian dysregulation in sleep pattern, mood, and hypothalamic-pituitary-adrenal (HPA) axis activity, often occurring in a sexually dimorphic manner, are characteristics of depression. However, the inter-relationships among circadian phase, HPA function, and depressive-like behaviors are not well understood. We investigated behavioral and neuroendocrine correlates of depressive/anxiety-like responses during diurnal (‘light’) and nocturnal (‘dark’) phases of the circadian rhythm in the open field (OF), elevated plus maze (EPM), forced swim (FST), and sucrose contrast (SC) tests. Plasma corticosterone (CORT) was measured after a) acute restraint and OF testing and b) FST. Both phase and sex significantly influenced behavioral responses to stress. Males were more anxious than females on the EPM in the light but not the dark phase. Further, the open:closed arm ratio was lower in the dark for females, but not males. By contrast, in the FST, females showed more “despair” (immobility) when tested in the dark, while phase did not affect males. Acute restraint stress increased OF activity in the light, but not the dark, phase. CORT levels were increased in both sexes following the FST, and in males and light phase females post-OF. As expected, females had higher CORT levels than males, even at rest, and this effect was more pronounced in the dark phase. Together, our data highlight the sexually dimorphic influences of circadian phase and stress on behavioral and hormonal responsiveness.     

硝苯吡啶对大鼠急性肾衰时肾功能及内源性内皮素释放的影响

目的和方法：在甘油致大鼠急性肾功能衰竭（ＡＲＦ）模型上，观察了硝苯吡啶对ＡＲＦ大鼠肾功能及内源性内皮素（ＥＴ）释放的影响。结果：ＡＲＦ大鼠肾皮质钙含量及血浆ＥＴ（ＰＥＴ）水平明显升高，肾功能严重受损，肾小管ＥＴ免疫反应阳性颗粒显著增多；而硝苯吡啶则使ＡＲＦ大鼠肾皮质钙含量及ＰＥＴ水平明显降低，肾小管ＥＴ免疫反应阳性颗粒明显减少，肾功能得到改善。结论：硝苯吡啶改善肾功能的作用可能与其抑制ＥＴ的合成与释放以及拮抗ＥＴ的生物学作用有关。     

HPA axis, respiration and the airways in stress—A review in search of intersections

Given clear connections between respiratory distress and subjective anxiety, it is not surprising that respiratory psychophysiologists have been interested in the psychobiology of anxiety. Given parallel links between anxiety and stress, it is not surprising that the hypothalamic-pituitary adrenal (HPA) stress system has also been a focus in anxiety research. However, despite extensive work in respiratory psychophysiology and stress neuroendocrinology - and evidence that these systems are jointly dysregulated in anxiety disorders - direct studies of their interactions are rare. This paper reviews evidence for scientific intersections, providing an overview of the HPA axis, its psychobiology, and shared neural substrates for HPA and respiratory control. We examine HPA hormone effects on respiration, immune/inflammatory mediators, and lung maturation. We also examine respiratory/dyspnea effects on HPA axis. There are clear points of intersection in the neuroscience of respiration and stress. Given the importance of both systems to an organism's ability to survive and adapt in challenging and changing environments, further study of their interactions is needed.     

Hyperactivity of the HPA axis is related to dietary restraint in normal weight women

The objective of our study was to investigate the relationship between hypothalamus/pituitary/adrenal (HPA) axis functioning and dietary restraint in normal weight (BMI between 20 and 25 kg/m²) men and women. We therefore assessed in 38 men and 38 women HPA axis functioning, through measuring 5-hour cortisol exposure and cortisol feedback functioning through a dexamethasone (4 mg) suppression test. Eating behavior was assessed through the Three Factor Eating Questionnaire and body composition through hydro densitometry and deuterium dilution method. No relationship between HPA axis functioning and dietary restraint was found in men. Normal weight women with a restraint score ≥ 9 showed increased cortisol concentrations over a 5-hour time period, increased cortisol concentrations after a dexamethasone (4 mg) suppression test, higher BMI, and higher body fat percentage, when compared to women with a restraint score < 9. Moreover, a positive relationship was found between cortisol concentrations over a 5-hour time period and dietary restraint in combination with the disinhibition score (R² = 0.23, p < 0.001). We conclude that in normal weight women hyperactivity of the HPA-axis is related to dietary restraint especially in combination with disinhibition.     

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

本文观察大鼠每天皮下注射皮质酮（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CRY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自然杀伤细胞活性减弱，T淋巴细胞产生IL-2、IFN－γ能力下降。提示：（1）外源性糖皮质激素剂量依赖性反馈抑制HPAT轴；（2）与此同时激活下丘脑单胺类递质，进一步支持糖皮质激素与儿茶酚胺共同构成HPAT重要调节因素的观点。     

Effect of foot deformity on conventional mechanical axis deviation and ground mechanical axis deviation during single leg stance and two leg stance in genu varum

We assessed the effect of foot deformity on the loading axis of lower limbs in 33 patients with genu varum (25 bilateral and eigth unilateral) caused by varying etiologies including achondroplasia, cerebral palsy, prior trauma, rickets, metaphyseal chondrodysplasia and primary osteoarthritis using single leg stance and both leg stance radiographs. Deviation at the knee from the hip ankle line (conventional) and hip foot line (centre of hip to centre of heel) was calculated. A comparison was made between single leg stance and two leg stance for tibiocalcaneal angle, mechanical axis angle, knee and ankle joint line convergence angle, conventional mechanical axis deviation (MADC) and ground mechanical axis deviation (MADG). In addition comparisons were also made among three groups formed depending on the tibiocalcaneal angle and MADC–MADG difference for all the above measurements.

Mechanical axis deviation (calculated using the two methods) varied with the talocalcaneal angle and single leg stance. Patients with a fixed subtalar varus and with severe genu varum, where the normal compensatory subtalar eversion could not compensate showed that conventional mechanical axis deviation was significantly higher by 3.4 ± 2.4 mm and ground mechanical axis deviation degrees was significantly higher by 3.8 ± 3.2 mm in single leg stance when compared to two leg stance (p < .0001).

Foot deformity should be included during preoperative evaluation and planning for knee deformity correction.