四逆散对慢性应激大鼠下丘脑-垂体-肾上腺轴作用的实验研究

目的研究调和肝脾之四逆散对慢性应激大鼠下丘脑-垂体-肾上腺轴（HPA轴）的影响。方法实验设正常组、模型1组、模型2组、四逆散组。除正常组外其余各组用电刺激法制备慢性应激动物模型,并给予相应的处理。观察大鼠行为学指标的变化,测定血浆皮质酮（CORT）、下丘脑促肾上腺皮质激素释放激素（CRH）和血浆促肾上腺皮质激素（ACTH）的含量,同时检测大鼠下丘脑CRH mRNA和垂体ACTH mRNA含量变化。结果四逆散能改善大鼠行为表现,降低大鼠血浆ACTH、下丘脑CRH、血浆CORT的含量及下丘脑CRH mRNA和垂体ACTH mRNA的过度表达。结论四逆散可有效调整慢性应激大鼠HPA轴的异常。     

“脑-肾轴”为命门说

命门作为人体生命的门户,受到历代医家的重视.但历代关于此问题的认识又多有不同,争议颇多.争论的焦点只是在于命门部位的确定上,而在其功能方面的认识上则几乎是一致的.根据历代医家的论述,并结合中医的现代研究成果,提出"脑-肾轴"为命门说,认为命门是一个与大脑及肾密切相关的功能器官,而非实质脏器.     

Decreased adrenocorticotropic hormone and cortisol responses to stress in healthy adults reporting significant childhood maltreatment.

BACKGROUND: Preclinical research findings suggest that exposure to stress and concomitant hypothalamus-pituitary-adrenal (HPA) axis activation during early development can have permanent and potentially deleterious effects. A history of early-life abuse or neglect appears to increase risk for mood and anxiety disorders. Abnormal HPA response to stress challenge has been reported in adult patients with major depressive disorder and posttraumatic stress disorder. METHODS: Plasma adrenocorticotropin hormone (ACTH) and cortisol reactivity to the Trier Social Stress Test were examined in healthy adults (n = 50) without current psychopathology. Subjects with a self-reported history of moderate to severe childhood maltreatment (MAL) (n = 23) as measured by the Childhood Trauma Questionnaire were compared with subjects without such a history (CTL) (n = 27). RESULTS: Compared with CTLs, MAL subjects exhibited significantly lower cortisol and ACTH baseline-to-peak deltas. A significant group effect was seen in the (repeated measures) cortisol response to the stress challenge, reflecting lower concentrations among MAL subjects. A significant group x time effect characterized the relatively blunted ACTH response of the MAL group. Emotional neglect (-.34, p = .02) and sexual abuse (.31, p = .03) strongly predicted maximal cortisol release. CONCLUSIONS: In adults without diagnosable psychopathology, childhood maltreatment is associated with diminished HPA axis response to a psychosocial stressor. Possible explanations for the finding are discussed.     

急性脑死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：采用施放免疫分析法（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者轴激素显著高于健康正常人组（Ｐ〈０．０１～     

Antisocial addicts: the importance of additional axis I disorders for the 28-month outcome

The association between additional co-morbid axis I disorders and the following 28-month course of drinking and mental distress was explored in a nation-wide representative sample (N = 100) of treatment-seeking alcoholics with antisocial personality disorder (ASPD). Diagnoses at admission were assessed with the Diagnostic Interview Schedule and follow-up status was assessed with a questionnaire and from informants. Only 24% had no additional diagnoses, 39% had an affective disorder, 43% panic/agoraphobia, 61% other anxiety disorders, and 47% were polysubstance abusers. Polysubstance abusers had more prior admissions, and were more often involved in fights, while additional anxiety disorder was associated with lower prevalence of drunken driving arrests. Relapse (87%) was best predicted by the number of prior admissions (odds ratio [OR] = 1.3), while affective disorders reduced the risk of relapse (OR = 0.2). Readmissions (55%) were least common among those with affective disorders (44%). Identifying axis I diagnoses, and in particular affective disorders among treatment-seeking ASPD alcoholics, is of substantial importance both in research and clinical practice.     

补肾药对心理应激下生殖轴内分泌网络影响的因子分析模型

为了探讨补肾药对心理应激下生殖轴内分泌网络的影响,从动物实验得到的原始生物学数据入手,对生殖轴内分泌网络的6个重要的生物调节因子做因子分析,建立了补肾药对心理应激下的生殖轴内分泌网络影响的因子分析模型。发现补肾药干预下各个生物因子之间的控制关系进一步复杂,各个生物因子之间相互制约,并有一种向均衡化方向发展的趋势,这是补肾药整合调节作用的结果,起到改善机体功能的作用。     

Gamma(2)-melanocyte-stimulating hormone suppression of systemic inflammatory responses to endotoxin is associated with modulation of central autonomic and neuroendocrine activities.

Central autonomic and neuroendocrine activities are important components of the host response to bacterial inflammation. We demonstrate that intravenous infusion of γ₂-melanocyte-stimulating hormone (γ₂-MSH), a potent autonomic regulating peptide, prevents lipopolysaccharide (LPS)-induced hypotension and tachycardia, and modulates the ACTH response to endotoxin. In the hypothalamic paraventricular nucleus, a major neuroendocrine and autonomic center, γ₂-MSH inhibits LPS-induced increases in CRF mRNA levels, but does not suppress LPS-augmented arginine vasopressin heteronuclear RNA expression. In the locus coeruleus, a brainstem noradrenergic center, γ₂-MSH inhibits LPS-induced increases in tyrosine hydroxylase mRNA levels. γ₂-MSH inhibits LPS-induced IL-1β gene expression in the brain, pituitary and thymus, and prevents increases in plasma NO levels. These findings reveal that γ₂-MSH attenuates systemic inflammatory responses to endotoxin and suggest that modulation of central autonomic and neuroendocrine activities by γ₂-MSH contributes to its anti-inflammatory effects.     

TIGIT及其配体CD155在“怒”应激大鼠胸腺细胞中的表达及其意义

目的探讨"怒"模型大鼠胸腺细胞中T细胞免疫球蛋白和ITIM结构域蛋白(TIGIT)及其配体CD155和血清促肾上腺皮质激素释放激素(CRH)、促肾上腺皮质激素(ACTH)、白细胞介素-2(IL-2)、白细胞介素-10(IL-10)表达情况,以及这些指标与胸腺细胞凋亡的相关性。方法将48只Wistar雄性大鼠随机分成对照组、模型7 d组、模型14 d组、模型21 d组,每组12只。除对照组外,其余各组以“社会隔离法”结合足底电击法复制精神应激“怒”模型大鼠。实验后测定大鼠体质量和胸腺指数,以苏木精-伊红(HE)染色观察大鼠胸腺组织的形态学改变,采用免疫印迹法检测各组大鼠胸腺细胞中TIGIT、CD155蛋白的表达水平,采用Tunel法检测胸腺细胞凋亡情况,采用酶联免疫吸附试验测定血清CRH、ACTH、IL-2、IL-10水平。结果实验后,4组大鼠体质量较试验前1 d升高(P<0.05),且“怒”模型各组大鼠体质量均低于对照组(P<0.05);实验后“怒”模型各组大鼠胸腺指数均低于对照组(P<0.05)。HE染色光学显微镜下(×400)可见“怒”模型各组大鼠大鼠胸腺皮质组织结构出现不同程度的损坏,幼稚T细胞布排紊乱无序或呈“条索状”堆积,细胞间隙缩小,细胞数量较对照组降低,细胞核染色变浅,呈淡紫色,并出现不同程度核固缩、核分裂、细胞溶解等凋亡细胞增多现象。4组大鼠胸腺细胞TIGIT蛋白表达水平比较,对照组<模型21 d组<模型14 d组<模型7 d组,其中模型7 d组、14 d组与其他各组胸腺细胞TIGIT蛋白表达水平差异均有统计学意义(P<0.05);“怒”模型各组大鼠胸腺细胞CD155蛋白表达水平高于对照组,差异均有统计学意义(P<0.05)。“怒”模型各组胸腺组织凋亡细胞吸光度高于对照组,差异有统计学意义(P<0.05)。模型7 d组、模型14 d组血清CRH、ACTH水平高于对照组及模型21 d组(P<0.05);“怒”模型各组IL-2水平低于对照组(P<0.05),且模型7 d组、模型14 d组低于模型21 d组(P<0.05);“怒”模型各组IL-10水平高于对照组(P<0.05),且模型14 d组高于模型7 d组及模型21 d组(P<0.05)。Pearson相关分析结果显示,TIGIT表达水平与CD155、ACTH、CRH及胸腺细胞凋亡程度呈正相关(P<0.05),与IL-2呈负相关(P<0.05),与IL-10及胸腺指数无相关性(P>0.05);CD155表达水平与TIGIT及胸腺细胞凋亡程度呈正相关(P<0.05),与IL-2呈负相关(P<0.05),与ACTH、CRH、IL-10及胸腺指数无相关性(P>0.05)。结论“怒”应激状态下,胸腺出现萎缩及凋亡细胞增多现象,可能是TIGIT-CD155与下丘脑-垂体-肾上腺轴、IL-10、IL-2共同作用所致,该研究为“怒”应激致使免疫损伤及疾病发生发展提供理论依据。     

Immunomodulation by probiotics and prebiotics in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the most prevalent primary malignancy in patients suffering from chronic liver diseases and cirrhosis. Recent attention has been paid to the involvement of the gut-liver axis (GLA) in HCC pathogenesis. This axis results from a bidirectional, anatomical and functional relationship between the gastrointestinal system and the liver. Moreover, the complex network of interactions between the intestinal microbiome and the liver plays a crucial role in modulation of the HCC-tumor microenvironment, contributing to the pathogenesis of HCC by exposing the liver to pathogen-associated molecular patterns, such as bacterial lipopolysaccharides, DNA, peptidoglycans and flagellin. Indeed, the alteration of gut microflora may disturb the intestinal barrier, bringing several toll-like receptor ligands to the liver thus activating the inflammatory response. This review explores the new therapeutic opportunities that may arise from novel insights into the mechanisms by which microbiota immunomodulation, represented by probiotics, and prebiotics, affects HCC through the GLA.