博古通今看脑垂——对华夏中医前身文字形象的研究考证

回眸中医历史只能望到秦汉二千五百年，中医的前身由夏商周时期断代文化淹没，无籍可考。幸有泥沙深埋了三千余年的甲骨金文出土，细啄精研，博古通令，呈现出上焦（胰岛），纨素（脑垂），膏盲（甲状腺），命门（肾上腺），完整的人体形态生物文字形象体系，由经络相串通，构成人的生命体。1909年至1949年，四十年的“西学东渐”与时俱进，五次世界诺贝尔医学奖授给了西学者，华夏古老的中医学体系固步自封出现了“数典忘祖”。尽管“古为今用喊的甚响，但中医发展远不如“西为中用”。本文对《素问》的‘素’字，“古为今用”，破译出华夏祖先对人们生物体——脑垂，它主宰着生命焦点，中医古老的精华。

EFFECTS OF DOPAMINE,ESTRADIOL AND TESTOSTERONE ON GONADOTROPIN RELEASE FROM THE PITUITARY FRAGMENTS OF Rana rugulosa

To understand the regulatory mechanisms of gonadotropin secretion in Rana rugulosa ,this study investigated the effects of dopamine (DA),estradiol (E 2) and testosterone (T) on the in vitro release of luteinizing hormone (LH) and follicle stimulating hormone (FSH) from the pituitary fragments of female Rana rugulosa using a static incubation system and radio immunoassay (RIA). The results indicated that DA at the concentration from 0 1?μmol/L to 10?μmol/L inhibited the release of LH and FSH from the pituitary fragments of sexually pre mature or hibernating individuals,and the inhibitory effects enhanced with increasing concentrations of DA. E 2 at 1?μmol/L and 10?μmol/L significantly stimulated the release of LH of sexually pre mature individuals,but inhibited their FSH release at 0 1?μmol/L to 10?μmol/L;T had no obvious effects on their FSH release,but significantly inhibited their LH release at 10?μmol/L. Neither E 2 nor T,at the concentration from 0 1?μmol/L to 100?μmol/L,had obvious effects on the release of LH and FSH of hibernating individuals. The data suggest that DA and sexual steroids may have direct regulatory actions on LH and FSH release at the pituitary level in Rana rugulosa ,and the action of sexual steroids may relate to the gonadal development stages (seasons).

EFFECTS OF ACUPUNCTURE ON THE HYPOTHALAMUS-PITUITARY-OVARY AXIS IN RATS WITH DYSMENORRHEA

Objective To observe the influence of acupuncture on hypothalamus-pituitary-ovary axis （HPOA） in rats with primary dysmenorrhea, and to explore its mechanisms. Methods Effects of acupuncture on the concentration level of β-endorphin （β-EP）, hypothalamic hormone （gonadotropin-releasing hormone, GnRH）, pituitary hormone （GnRH receptor GnRH-R, follicle stimulating hormone FSH, luteinizing hormone LH） and ovarian hormone （estrodiol E2, estrodiol receptor ER, progesterone P and progesterone receptor PR） were observed in dysmenorrheic rats. Results After receiving acupuncture treatment, the levels of 13- EP, GnRH, GnRH-R, FSH, LH, E2, ER, P and PR were changed, and this suggested that acupuncture had a regulative action on HPOA in dysmenorrheic rats. Conclusion The mechanism of acupuncture acting on the HPOA with primary dysmenorrhea might be its regulating role to the gonadal hormone of HPOA and its corresponding receptor expression.

Distribution of Oxytocin Hypothamic-Picuitary-Ovary Axis in Guangxi Local Buffalo

To study the association of oxytocin (OT)'s distribution in hypothalamatic,pituitary and ovary,and understand how the OT secrete releasing in hypothalamus,pituitary and ovaries,the paraffin section immunohistochemistry SuperPicTureTM two step method was used to detect the distribution of OT in hypothalamatic-pituitary-ovary axis of five femal Guangxi local buffalo. The test results could provide morphology according to study the OT's synthesis and mechanism of action,and could play reference and directions part in breeding Guangxi local buffalo. The test results display:oxytocin immuno reactive (OT-IR) neuronsw eremainly distributed arcuate nucleus,supraoptic nucleus and paraventricular nucleus,and OT-IR neurons was also found in ventromedial nucleus,ventrolateralis nucleus,suprachiasmaticus nucleus,dorsomedial nucleus,mamillary body,anterior hypothalamic nucleus and so on. The OT immunoactive production was found in pituitary and few OT-IR nerve fibers extended to post pituitary from hypophyseal stalk and medium eminence. In ovaries,OT immunoactive productions were only distributed in germinal epithelium cells,granulosa cells and lutein cells. The OT was first discovered in singulorum link of hypothalamatic-pituitary-ovary axis of Guangxi local buffalo. The OT immunoactive neurons were first discovered in every main nucleus of Guangxi local buffalo hypothalamus,especially distributed in arcuate nucleus,supraoptic nucleus and paraventricular nucleus.

Regulative Actions of the Chinese Drugs for Tonifying the Kidney on Gene Expression of the Hypothalamic GnRH,Pituitary FSH,LH and Osteoblastic BGP

It is found that the drugs for nourishing yin to reduce pathogenic fire can significantly down-regulate,and the drugs for tonifying the kidney to replenish essence can up-regulate mRNA expression of the hypothalamic GnRH,pituitary FSH,LH and osteoblastic BGP,indicating that the Chinese drugs for tonifying the kidney can regulate gene expression of the hypothalamic GnRH,pituitary FSH,LH,and osteoblastic BGP,which is possibly one of the main mechanisms of the Chinese drug for tonifying the kidney,regulating ephebic development process and improving skeletal development in sexual precocity children.

Pituitary hormone circadian rhythm alterations in cirrhosis patients with subclinical hepatic encephalopathy

AIM:To analyze pituitary hormone and melatonin circadian rhythms, and to correlate hormonal alterations with clinical performance, hepatic disease severity and diagnostic tests used for the detection of hepatic encephalopathy in cirrhosis. METHODS:Twenty-six patients with cirrhosis were enrolled in the study. Thirteen patients hospitalized for systemic diseases not affecting the liver were included as controls. Liver disease severity was assessed by the Child-Pugh score. All patients underwent detailed neurological assessment, electroencephalogram (EEG), brain magnetic resonance imaging (MRI), assays of pituitary hormone, cortisol and melatonin, and complete blood chemistry evaluation. RESULTS: Pituitary hormone and melatonin circadian patterns were altered in cirrhosis patients without clinical encephalopathy. Circadian hormone alterations were different in cirrhosis patients compared with controls. Although cortisol secretion was not altered in any patient with cirrhosis, the basal cortisol levels were lowand correlated with EEG and brain MRI abnormalities. Melatonin was the only hormone associated with the severity of liver insufficiency. CONCLUSION: Abnormal pituitary hormone and melatonin circadian patterns are present in cirrhosis before the development of hepatic encephalopathy. These abnormalities may be early indicators of impending hepatic encephalopathy. Factors affecting the human biologic clock at the early stages of liver insufficiency require further study.

IN VITRO CELL CULTURE AND HORMONE RADIOIMMUNOASSAY OF HUMAN PITUITARY ADENOMAS

Tissues from 30 human pituitary adenomas are monolayer-cell-cultured in vitro.Hormone secretion of GH, PRL, TSH, LH and FSH by cells into medium is detected by radioimmunoassay. The pattern and amount of hormone(s) in the medium are used to determine the nature of the cells and thus to establish functional classification of pituitary adenomas. The results show that cell culture technique provides an easy and suitable mode for investigating the nature of pituitary adenomas. Hormone radioimmunoassay of culture medium is precise and reliable and represents the whole adenoma tissue. Further studies can lead to clearer understandings of the pathology of pituitary adenomas.

MAGNETIC RESONANCE IMAGES OF THE HYPOTHALAMIC-PITUITARY AREA IN IDIOPATHIC GROWTH DEFICIENCY

In order to describe the magnetic resonance imaging (MRI) findings in hypothalamic-pituitary area and its clinical relevance in patients with idiopathic growth hormone deficiency (IGHD), the MR imagings of 26 patients with IGHD were analyzed. On MRI, 24 out of 26 cases (92. 3%) showed apparent pituitary upper margin depression; 8 out of 26 cases (30. 8%) showed definite pituitary stalk transection; 22 out of 26 cases (84. 6%) showed absence of the normal posterior pituitary bright spot. The bright lipidlike signal on T1W1 images at the median eminence distal to the breaking point (so-called ectopic posterior lobe) was found in 4 out of 26 cases (15. 4%). According to the MRI findings of the pituitary stalks, the 26 cases were divided into three groups; group A of 8 cases (31%) characterized by the definite transaction of stalk; group B of 13 cases (50%) defined by the possible stalk transection; and group C of 5 cases (19%) with no definite stalk transection.MRI findings were consistent with the clinical and endocrine tests. The stalk transection was statistically significantly difference in insulin test, L-dopa/p test, and height standard deviation score (P< 0.05). The MRI of hypothalamic-pituitary area may differentiate partial IGHD form stalk-transected, doubtful transection and without transection.

Pituitary prolactin adenoma with Toxoplasma gondii infection

Objective: To report two recent cases of pituitary adenoma associated with Toxoplasma gondii (T.Gondii) infection.Methods: Histological changes were observed in H & E and PAS staining sections microscopically.Immunohistochemistry was performed to classify the pituitary tumors and to confirm the diagnosis of T.gondii.Results: The cases were 43- and 19-year-old females, in which the latter one was a recurring case, and radiology examination showed that tumors existed in sellar region.Microscopically, the tumors consisted of small homogenous polygonal or round cells with abundant eosinophilic granular cytoplasm.Immunohistochemistry revealed they were prolactin-producing adenomas.Interestingly, we found toxoplasma infection in the tumor tissues, being confirmed by T.gondii sepicific antibody immunohistochemistry.Conclusion: The association of pituitary adenoma with toxoplasma raises the possibility that T.gondii may be involved in the development of certain cases of pituitary adenoma.

Effects of repetitive transcranial magnetic stimulation on hypothalamic-pituitary-adrenal axis of patients with depression

Objective： To investigate the effects of sleep electroencephalogram-modulated repetitive transcranial magnetic stimulation （SEM-rTMS） and conventional rTMS （C-rTMS） on the activity of hypothalamic-pituitary-adrenal （HPA） axis in patients with depression. Methods： In a double-blind, randomized controlled trial, 164 patients diagnosed with depression were randomized to treatment with SEM-rTMS （n=57）, C-rTMS （n=55） or sham rTMS （n=52） for 30 rain every day for 10 d. Before and after treatment plasma concentrations of adrenocorticotropic hormone （ACTH） and cortisol （CORT） were measured, and the 24-item Hamilton Depression Rating Scale （HAMD-24） was used for assessment. Results： The HAMD-24 scores and plasma ACTH and CORT concentrations of these depressive patients before treatment were significantly different from those of the normal control group （P〈0.05）. The HAMD-24 scores and plasma ACTH and CORT concentrations in the SEM-rTMS group and conventional rTMS group were decreased significantly （P〈0.05）. There was a significant positive correlation between the HAMD-24 scores and plasma ACTH （n=240, r=0.105, P=0.048） and CORT concentrations （n-240, r=0.126, P=0.023） in the patients with depression before and after treatment. Conclusion： The antidepressant effect of rTMS, including SEM-rTMS, may be related to its decreasing HPA axis activity. （This trail was registered. No： ChiCTR-TRC-00000465）

Increased expression level of corticotropin-releasing hormone in the amygdala and in the hypothalamus in rats exposed to chronic unpredictable mild stress

Objective Corticotropin-releasing hormone（CRH）plays an important role in neuroendocrine,autonomic and behavioral responses to stressors.In the present study,the effect of chronic unpredictable mild stress（CUMS）on CRH neurons was investigated in rat brain.Methods The rats were exposed to one of the stressors each day for 21 d.Immunostaining was performed to detect the CRH-positive neurons in the paraventricular nucleus（PVN）of the hypothalamus and in amygdala.Results After the stress protocol,the animals showed a reduction in body weight gain as well as reduced sucrose preference and locomotor activity.Interestingly,the CRH neurons in both PVN and central nucleus of the amygdala（CeA）were stimulated by CUMS.The densities of CRH-containing neurons in both PVN and CeA were significantly higher than those in control group.Conclusion The CRH systems in PVN and CeA may both contribute to depression-like behaviors during CUMS.

Sini Powder extract produces antidepressant-like effects in a chronic social defeat stress model of depression in tree shrews

Sini Power（SP） is a famed traditional Chinese formula that has long been used to treat depression. Here, we investigated the effects and possible mechanisms of SP extract on an established model of depression： chronic stressed tree shrew, which mimics the human condition of social stress. The animals were divided into 4 groups. Except for the na？ve group, the other animals were subjected to daily social defeat stress for 5 weeks, and during the last 4 weeks treated with SP extract（3.6 g/kg/d）, fluoxetine（15 mg/kg/d）, and vehicle, respectively. The results showed that SP extract could reverse body weight loss to a certain extent and reduce the levels of urine/serum cortisol that were initially increased by chronic social defeat. In addition, SP extract increased hippocampus norepinephrine concentrations. Our data suggested that SP extract had positive effects on the main depression symptoms in the chronic stressed tree shrew model and that it may be used to help control hypothalamic-pituitary-adrenal axis hyperactivity.

Regulatory mechanism of hormones of the pituitary-target gland axes in kidney-Yang deficiency based on a support vector machine model

OBJECTIVE:To study the development mechanism of kidney-Yang deficiency through the establishment of support vector machine models of relevant hormones of the pituitary-target gland axes in rats with kidney-Yang deficiency syndrome.METHODS:The kidney-Yang deficiency rat model was created by intramuscular injection of hydrocortisone,and contents of the hormones of the pituita- ry-thyroid axis:thyroid stimulating hormone(TSH),3,3',5-triiodothyronine(T_3) and thyroxine(T_4);hormones of the pituitary-adrenal gland axis:adrenocorticotropic hormone(ACTH) and Cortisol(CORT);and hormones of the pituitary-gonadal axis:luteinizing hormone(LH),follicle-stimulating hormone(FSH),and testosterone(T),were determined in the early,middle,and advanced stages.Ten support vector regression(SVR) models of the hormones were established to analyze the mutual relationships among the hormones of the three axes.RESULTS:The feedback control action of the pituitary-adrenal axis began to lose efficacy from the middle stage of kidney-Kong deficiency.The contents all hormones of the three pituitary-target gland axes decreased in the advanced stage.Relative errors of the jackknife test of the SVR models all were less than 10%.CONCLUSION:Imbalances in mutual regulation among the hormones of the pituitary-target gland axes,especially loss of effectiveness of the pituitary-adrenal axis,is one pathogenesis of kidney-Yang deficiency.The SVR model can accurately reflect the complicated non-linear relationships among pituitary-target gland axes in rats with of kidney-Yang deficiency.

Influence of Acupuncture on HPA Axis in a Rat Model of Chronic Stress-induced Depression

Objective： To investigate the neurobiological mechanism of depression pathogenesis and reveal the mechanism of acupuncture treatment of depression. Methods： Wistar rats were selected for subjects. A rat model of depression was made by individually housing with unpredicted chronic moderate stimuli. Changes in behavior and hypothalamus-pituitaryadrenocortical axis were examined in rat models of stress-induced depression. Meanwhile, the intervening effect of acupuncture was evaluated and the curative effects of different acupuncture methods compared. Results： CORT and ACTH contents of serum were significantly higher in the model and normal saline groups than in the control group （P〈0.05）, significantly lower in the hand acupuncture and electroacupuncture groups than in the model group （P〈0.05） and significantly lower in the medication group than in the normal saline group （P〈0.05）. There were no significant differences between the hand acupuncture, electroacupuncture and medication groups. Conclusion： Acupuncture of Baihui（GV 20） and Taichong （LR 3） has a marked antidepressant effect. Its mechanism may be related to the regulation of HPA axis by acupuncture.

Effects of neuro-immuno-modulation on healing of wound combined with local radiation injury in rats

Purpose： To investigate effects of neuro-immuno-modulation on wound healing by observing changes of cytokines and hypothalamic-pituitary-adrenal （HPA） axis hormones in acute stress reaction in rats with wound and combined local radiation injury. Methods： Sixty female Wistar rats （weighting 200 ± 20 g） were randomly divided into normal control group, wound group and combined wound-local radiation （CWR） group （25 Gy local radiation post wound）, 20 rats in each group. Contents of IL-1β, IL-6 and IFN-γ and IL-4 in serum were measured and changes of adrenocorticotropic hormone （ACTH） and glucocorticoid （GC） in serum were analyzed by using enzyme-linked immunosorbent assay and radioimmunologic assay, respectively at different time points post wound and radiation. Results： （1） The level of IFN-γ, one of the Thl cell cytokines increased significantly at 14 d post CWIL which was markedly higher than that in control group and wound group. However, the level of IL-4, IL-1β and IL-6, one of the Th2 cell cytokines, did not show obvious change. （2） Ratio of Thl/Th2 （IFN-γ/IL-4） in wound group and CWR group increased significantly at 7 d after wound and radiation, which suggested that Thl/Th2 balance drifted to Thl immune response. The ratio of Thl/Th2 in wound group returned to the normal level up to 14 d after the wound and radiation, while the Thl/Th2 ratio in CWR group increased persistently and was much higher than that in control and wound groups. （3） Level of serous ACTH and CC in CWR group increased at 3 d post wound and radiation, and among them, level of CC showed statistically significant increase, which was much higher than that in control and wound groups. Conclusion： Level of serous neurohormone CC in rats increased significantly immediately after wound and radiation; while the level of IFN-γ showed significant increase only up to 14 d after wound and radiation, and the Th1/Th2 imbalance sustained till 28 d post wound and radiation. In order to reduce acute damage caused by CWR, organic immune system and nerve system showed up a marked regulate effects simultaneously and mutually. Nonetheless, the excessive stress induced by CWR causes distur- bance of immunoregulation, which is one of the key reasons for delayed wound healing in CWR.

Effects of Electro-acupuncture on Hypothalamic-PituitaryAdrenal Index and Corticotropin Releasing Hormone mRNA Expression of Rats with Chronic Fatigue Syndrome

Objective： To investigate the mechanism of electroacupuncturein treating chronic fatigue syndrome（CFS） in term of the neuro-endocrine system by observing the regulative effect of EA on hypothalamic-pituitary-adrenal index （HPA index） and corticotropin releasing hormone mRNA （CRH mRNA） in CFS model rats. Methods： The rats were randomly divided into control group, model group, and electroacupuncture group. Model and electroacupuncture groups were forced to swim in cold water to make CFS model, while rats in electroacupuncture group were treated with electroacupuncture treatment at the same time. Electroacupuncture group was given at Baihui（GV 20） and Zusanli（ST 36）. Evaluation of the model was processed according to the behavior changes of the rats. Hypothalamic, pituitary, and adrenal were weighted to calculate HPA index. CRH mRNA in hypothalamic was measured by fluorescence quantitative polymerase chain reaction （FQPCR）. Results： The model rats had behavior changes, and both physical and mental fatigue was observed. HPA index raised and expression of CRH mRNA in hypothalamus increased in CFS rats. After electroacupuncture treatment, the physical and mental fatigue was improved, and the hypothalamic index and CRH mRNA decreased significantly, while the pituitary and adrenal index only had little decrease. Conclusion： Cold water swim press could mimic the pathogenesis and make similar manifestations in rats with the common clinical symptoms. CFS has close relationship with increase of HPA index and CRH mRNA expression. Electroacupuncture can regulate the function of HPA axis to deal with CFS.