Effect and mechanisms of sacral nerve stimulation on visceral hypersensitivity mediated by nerve growth factor

To investigate the efficacy of sacral nerve stimulation (SNS) on nerve growth factor (NGF) mediated visceral sensitivity in normal rat and visceral hypersensitivity model rats. 120 male newborn rats were randomly divided into 6 groups: group A was normal model group; group B ~ F were all sensitized with acetic acid enema and grouped again. Group c2 was given NGF antagonist, d2 group was given NGF agonist, e2 group was given PI3K inhibitor, and f2 group was given PLC‐γ inhibitor. After treatment, the expression of NGF, TrKA, PI3K, AKT, PLC‐γ, NF‐κB, TRPV1, pTRPV1 and intracellular Ca²⁺ content were detected. The expression of protein TRPV1 and pTRPV1 was increased, and Ca²⁺ was increased in the visceral hypersensitive group. NGF, TrKA in NGF antagonist group, PI3K, AKT, NF‐κB in PI3K inhibitor group, PLC‐γ in PLC‐γ inhibitor group were all almost not expressed. The relative expression of NGF, TrKA, PI3K, AKT, PLC‐γ and NF‐κB in NGF antagonist group was lower than that in visceral hypersensitivity group and NGF activator group (P < .01). The relative expression of NGF, TrKA, PI3K and AKT mRNA in NGF antagonist group was lower than that in the normal model group (P < .01). There was no significant difference in the relative expression of PLC‐γ and NF‐κB mRNA (P > .05). The expression level of MAPK, ERK1 and ERK2 in visceral hypersensitivity group was higher than that in PI3K inhibitor group and PLC‐γ inhibitor group. The normal group Ca²⁺ curve was flat, and the NGF agonist group had the highest Ca²⁺ curve peak. Calcium concentration in visceral hypersensitivity group was higher than that in PI3K inhibitor group and that in PLC‐γ inhibitor group was higher than that in NGF antagonist group. The binding of TrkA receptor to NGF activates the MAPK/ERK pathway, the PI3K/Akt pathway and the PLC‐γ pathway, causing changes in the fluidity of intracellular and extracellular Ca²⁺, resulting in increased sensitivity of visceral tissues and organs.     

Anti-inflammatory effect of acute stress on experimental colitis is mediated by cholecystokinin-B receptors

We aimed to investigate the effects of electric shock (ES) on the course of experimental colitis and the involvement of possible central and peripheral mechanisms. In Sprague-Dawley rats (n = 190) colitis was induced by intracolonic administration 2,4,6-trinitrobenzenesulfonic acid (TNBS). The effects of ES (0.3-0.5 mA) or the central administration of corticotropin-releasing factor (CRF; astressin, 10 microg/kg) or cholecystokinin (CCKB; 20 microg/kg) receptor antagonists and peripheral glucocorticoid receptor (RU-486; 10 mg/kg) or ganglion (hexamethonium; 15 mg/kg) blockers on TNBS-induced colitis were studied by the assessment of macroscopic score, histological analysis and tissue myeloperoxidase activity. ES reduced all colonic damage scores (p < 0.05-0.01), while central CRF (p < 0.05-0.001) and CCKB receptor (p < 0.05-0.01) blockers or peripheral hexamethonium (p < 0.05-0.01) and RU-486 (p < 0.05) reversed stress-induced improvement. ES demonstrated an anti-inflammatory effect on colitis, which appears to be mediated by central CRF and CCK receptors with the participation of hypothalamo-pituitary-adrenal axis and the sympathetic nervous system.     

Angiotensinergic neurons in sympathetic coeliac ganglia innervating rat and human mesenteric resistance blood vessels

In contrast to the current belief that angiotensin II (Ang II) interacts with the sympathetic nervous system only as a circulating hormone, we document here the existence of endogenous Ang II in the neurons of rat and human sympathetic coeliac ganglia and their angiotensinergic innervation with mesenteric resistance blood vessels. Angiotensinogen - and angiotensin converting enzyme-mRNA were detected by using quantitative real time polymerase chain reaction in total RNA extracts of rat coeliac ganglia, while renin mRNA was untraceable. Cathepsin D, a protease responsible for cleavage beneath other substrates also angiotensinogen to angiotensin I, was successfully detected in rat coeliac ganglia indicating the possibility of existence of alternative pathways. Angiotensinogen mRNA was also detected by in situ hybridization in the cytoplasm of neurons of rat coeliac ganglia. Immunoreactivity for Ang II was demonstrated in rat and human coeliac ganglia as well as with mesenteric resistance blood vessels. By using confocal laser scanning microscopy we were able to demonstrate the presence of angiotensinergic synapses en passant along side of vascular smooth muscle cells. Our findings indicate that Ang II is synthesized inside the neurons of sympathetic coeliac ganglia and may act as an endogenous neurotransmitter locally with the mesenteric resistance blood vessels.     

世界遗产视角下的国外自然圣境保护实践进展与代表性方法研究

自然圣境（sacred natural sites,简称SNS）是自然保护地体系的重要构成,也是典型的文化景观。它们作为人与自然互动的历史记录,所蕴藏的文化价值是其赖以存在的根基。从单纯的自然保护到融合文化价值的整体性保护,反观国外SNS保护工作的方向性转变,有助于在全球发展主义时代背景下从“术”的层面重新审视中国SNS保护工作中面临的诸多挑战,对于推进中国生态文明建设具有重大意义。从世界遗产角度,在阐述SNS概念的基础上,全面梳理不同国际组织机构参与下的SNS保护实践进展;总结目前在其保护中涉及的景观方法和生物文化多样性方法等主流保护方法;最后指出在国家公园体制背景下,充分开展本土SNS基础调研,完善相关规划并确立保护条例,在遗产地可持续发展的基础上协调SNS中的人际间及人与其他物种的公平关系是中国SNS保护成功的关键。