Pregnancy and sex steroid hormones enhance circulating calcitonin gene-related peptide concentrations in rats

Calcitonin-gene-related peptide (CGRP) is a 37 amino acid neuropeptide synthesized primarily in dorsal root ganglia (DRG) and distributed widely in the perivascular nerves, suggesting that this peptide may play a role in the regulation of peripheral vascular tone. Since female sex steroid hormones have been implicated in the regulation of peripheral vascular tone during pregnancy, we postulated that they may alter the concentration of CGRP in the circulation and thus modulate the increased blood flow observed during pregnancy. In the present study, we measured changes in plasma concentrations of CGRP in non-pregnant, pregnant, and post-partum rats. Groups of ovariectomized rats were treated s.c. for 3 days either with 17beta-oestradiol (2.5 microg per injection twice daily), progesterone (2 mg per injection twice daily), or vehicle. Another group of adult, non-pregnant rats at dioestrus stage of the oestrous cycle was also used in this study. Plasma concentrations of CGRP were higher (P < 0.05) in rats on day 19 of pregnancy (22.0 +/- 3.0 pmol/l) compared to that during delivery (5. 0 +/- 2.0), post-partum day 2 (2.0 +/- 0.7) or in non-pregnant (4.9 +/- 1.6) state. Furthermore, in adult ovariectomized (6.0 +/- 0.6) rats, plasma CGRP concentrations were increased significantly (P < 0. 05) by oestradiol (10.0 +/- 1.0), progesterone (9.5 +/- 1.0) and oestradiol + progesterone (14.0 +/- 1.0). Thus, circulating concentrations of CGRP are elevated during pregnancy and by oestrogen and progesterone, suggesting that the elevated concentrations of CGRP may play an important role in vascular adaptations that occur during pregnancy.     

降钙素基因相关肽在大鼠纹状体内分布的生后发育研究

目的：了解大鼠纹状体内的钙离子基因相关肽（ＣＧＲＰ）在纹状体和苍白球内分布的生后发育变化。方法：对出生后１天至１年的大鼠脑行冠状组织切片,尔后进行ＣＧＲＰ的ＡＢＣ法免疫细胞化学染色。结果：ＣＧＲＰ在纹状体的近尾侧部主要分布在纹状体的边缘区,为大量的密度很高的免疫反应阳性纤维,在纹状体的远尾侧部几乎遍布整个尾壳核,但以其外侧缘和腹侧为多,在尾壳核的外侧部形成一条浓密的阳性纤维带。苍白球内可见少量的ＣＧＲＰ免疫反应纤维存在,多靠近苍白球的内侧缘。ＣＧＲＰ在纹状体内分布的生后发育特征为：Ｐ０１时边缘区有少量阳性纤维分布,Ｐ０５时形成带状纤维分布,Ｐ１０时尾壳核腹外侧部有阳性纤维分布,Ｐ３０以后同成年。结论：ＣＧＲＰ在纹状体和苍白球内具有独特的分布特征和生后发育规律。     

降钙素基因相关肽在哮喘豚鼠内脏传入系统的定量分析

本文应用放射免疫分析方法研究了实验性哮喘豚鼠与下呼吸道有关的内脏传入系统内降钙素基因相关肽含量的变化 ,藉以探讨降钙素基因相关肽在哮喘发病时的作用机制。结果表明 ,哮喘豚鼠与下呼吸道有关的内脏传入系统 (结状神经节、C7～T5 节段脊神经节和脊髓后角、孤束核等处 )中的降钙素基因相关肽含量明显高于各对照组 ( P<0 .0 5)。本研究提示 ,下呼吸道和肺的内脏传入成分中的降钙素基因相关肽可能参与哮喘发病的病理生理过程。     

妊高征患者血浆AM、CGRP、sICAM-1及THcy水平变化的意义

目的：探讨妊娠高血压综合征（妊高征）患者血浆肾上腺髓质素（AM）、降钙素基因相关肽（CGRP）、细胞间黏附分子-1（sICAM-1）及总同型半胱氨酸（THcy）水平的变化与患者发病及其进展的关系。方法：35名非孕妇女、34名正常孕妇（对照组）及35例妊高征患者的血浆AM和CGRP含量采用放射免疫分析;血浆sI-CAM-1水平采用酶联免疫分析。THcy则应用化学发光免疫分析法测定。结果：表1可见,血浆AM水平对照组较非孕妇女组水平略升高,但无显著统计学意义（P〉0.05）;治疗前组与对照组比较升高非常显著（P〈0.01）;治疗后水平下降明显,但与对照组比较升高仍存在显著性（P〈0.05）。CGRP水平对照组略低于非孕妇女组,但并不存在统计差异（P〉0.05）,治疗前组与对照组比较下降非常显著（P〈0.01）;经治疗水平显著升高,与对照组比较已无显著差异（P〉0.05）。sICAM-1水平对照组较非孕妇女组水平略高,但无显著统计学意义（P〉0.05）;治疗前组与对照组比较升高显著（P〈0.05）;治疗后水平下降明显,但与对照组比较差异已无显著性（P〉0.05）。THcy水平的统计学变化与sICAM-1一致。结论：妊高征患者血浆四项指标的测定对于了解和认识其发病机理及预估病情有帮助。     

运动对大鼠冠状血管系统降钙素基因相关肽的影响

目的探讨不同强度运动对降钙素基因相关肽（CGRP）在冠状血管组织中表达的影响及其作用机制。方法健康雄性SD大鼠60只,随机分为对照组、小强度运动组、中等强度运动组和大强度运动组。建立8周不同强度运动训练动物模型,采用免疫组织化学法和计算机图像分析技术对冠状血管组织CGRP的表达进行分析。结果小强度运动组冠状血管组织CGRP表达较对照组变化不明显,中等强度运动组冠状血管组织CGRP表达明显高于对照组（P〈0．05）,大强度运动组冠状血管组织CGRP表达明显低于对照组（P〈0．05）。结论长期中等强度运动使冠状血管组织CGRP分泌增加,改善冠状循环和心肌的血液供应,增强了CGRP对心脏的保护作用。     

Transient receptor potential vanilloid 1 expression and function in splenic dendritic cells: a potential role in immune homeostasis

Neuro‐immune interactions, particularly those driven by neuropeptides, are increasingly implicated in immune responses. For instance, triggering calcium‐channel transient receptor potential vanilloid 1 (TRPV1) on sensory nerves induces the release of calcitonin‐gene‐related peptide (CGRP), a neuropeptide known to moderate dendritic cell activation and T helper cell type 1 polarization. Despite observations that CGRP is not confined to the nervous system, few studies have addressed the possibility that immune cells can respond to well‐documented ‘neural’ ligands independently of peripheral nerves. Here we have identified functionally relevant TRPV1 on primary antigen‐presenting cells of the spleen and have demonstrated both calcium influx and CGRP release in three separate strains of mice using natural agonists. Furthermore, we have shown down‐regulation of activation markers CD80/86 on dendritic cells, and up‐regulation of interleukin‐6 and interleukin‐10 in response to CGRP treatment. We suggest that dendritic cell responses to neural ligands can amplify neuropeptide release, but more importantly that variability in CGRP release across individuals may have important implications for immune cell homeostasis.     

血浆ET-1和CGRP含量测定对脑出血病人的应用价值

目的 :探讨血浆内皮素 (ET)和降钙素基因相关肽 (CGRP)在脑出血病人急性期与恢复期中的变化。方法 :采用放射免疫分析技术 ,对 4 2例脑出血病人的急性期与恢复期 ,分别测定血浆ET和CGRP含量 ,并用 35例健康对照人员作比较。结果 :脑出血病人血浆ET含量明显高于对照组 (p <0 0 1) ,治疗后有所下降 ;而血浆CGRP含量 ,在脑出血的急性期 ,显著高于对照组 (p <0 0 1) ,恢复期降为正常。结论 :血浆ET和CGRP在脑出血的急性期显著升高 ,并与脑损伤程度有关 ,提示神经肽参与出血性脑损伤的发生发展过程     

降钙素治疗延缓卵巢切除大鼠腰椎间盘退变

目的:观察降钙素对卵巢切除大鼠腰椎骨量及椎间盘退变的影响。方法:SD大鼠分为基线对照组、假手术组、卵巢切除组及降钙素治疗组,进行腰椎节段骨密度和骨形态计量学分析,观察椎间盘的组织形态学改变。结果:卵巢切除组骨量较对照组和降钙素治疗组显著下降,骨转化指标明显提高。降钙素治疗组的腰椎间盘组织学评分较卵巢切除组显著下降。结论:卵巢切除大鼠椎间盘退变可能是骨量减少引起的脊柱力学改变所致,降钙素治疗可以预防骨量丢失并延缓其腰椎间盘退变。     

Stimulus-evoked release of neuropeptides is enhanced in sensory neurons from mice with a heterozygous mutation of the Nf1 gene

Neurofibromatosis type I is a common autosomal dominant disease characterized by formation of multiple benign and malignant tumors. People with this disorder also experience chronic pain, which can be disabling. Neurofibrinomin, the protein product of the NF1 gene (neurofibromin gene (human)), is a guanosine triphosphate activating protein for p21(ras). Loss of NF1 results in an increase in activity of the p21(ras) transduction cascade. Because of the growing evidence suggesting involvement of downstream components of the p21(ras) transduction cascade in the sensitization of nociceptive sensory neurons, we examined the stimulus-evoked release of the neuropeptides, substance P and calcitonin gene-related peptide, from primary sensory neurons of mice with a mutation of the Nf1 gene (neurofibromin gene (mouse)) (Nf1+/-). Measuring immunoreactive substance P and immunoreactive calcitonin gene-related peptide by radioimmunoassay, we demonstrated that capsaicin-stimulated release of neuropeptides is three to five-fold higher in spinal cord slices from Nf1+/- mice than from wildtype mouse tissue. In addition, the potassium and capsaicin-stimulated release of immunoreactive calcitonin gene-related peptide from cultures of sensory neurons isolated from Nf1+/- mice was more than double that from cultures of wildtype neurons. Treatment of wildtype sensory neurons with nerve growth factor for 5-7 days mimicked the enhanced stimulus-evoked release observed from the Nf1+/- neurons. When nerve growth factor was removed 48 h before conducting release experiments, nerve growth factor-induced augmentation of immunoreactive calcitonin gene-related peptide release from Nf1+/- neurons was more pronounced than in Nf1+/- sensory neurons that were treated with nerve growth factor continuously for 5-7 days. Thus, sensory neurons from mice with a heterozygous mutation of the Nf1 gene that is analogous to the human disease neurofibromatosis type I, exhibit increased sensitivity to chemical stimulation. This augmented responsiveness may explain the abnormal pain sensations experienced by people with neurofibromatosis type I and suggests an important role for guanosine triphosphate activating proteins, in the regulation of nociceptive sensory neuron sensitization.     

Procalcitonin in sepsis and systemic inflammation: a harmful biomarker and a therapeutic target

The worldwide yearly mortality from sepsis is substantial, greater than that of cancer of the lung and breast combined. Moreover, its incidence is increasing, and its response to therapy has not appreciably improved. In this condition, the secretion of procalcitonin (ProCT), the prohormone of calcitonin, is augmented greatly, attaining levels up to thousands of fold of normal. This hypersecretion emanates from multiple tissues throughout the body that are not traditionally viewed as being endocrine. The serum values of ProCT correlate with the severity of sepsis; they recede with its improvement and worsen with exacerbation. Accordingly, as highlighted in this review, serum ProCT has become useful as a biomarker to assist in the diagnosis of sepsis, as well as related infectious or inflammatory conditions. It is also a useful monitor of the clinical course and prognosis, and sensitive and specific assays have been developed for its measurement. Moreover, it has been demonstrated that the administration of ProCT to septic animals greatly increases mortality, and several toxic effects of ProCT have been elucidated by in vitro experimental studies. Antibodies have been developed that neutralize the harmful effects of ProCT, and their use markedly decreases the symptomatology and mortality of animals that harbour a highly virulent sepsis analogous to that occurring in humans. This therapy is facilitated by the long duration of serum ProCT elevation, which allows for a broad window of therapeutic opportunity. An experimental groundwork has been established that suggests a potential applicability of such therapy in septic humans.