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Role of sensory neurons to gender difference in the responses against stress.

感觉神经元在应激反应中性别差异的作用。

基本信息

批准号：
16591810
负责人：
UCHIBA Mitsuhiro
金额：
$ 2.37万
依托单位：
Kumamoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

项目摘要

Sensory neurons play a critical role in reducing stress-induced gastric mucosal injury by releasing calcitonin gene-related peptide (CGRP) through an increase in gastric mucosal levels of prostacyclin (PGI2). Since estrogen enhances the nerve growth factor-mediated CGRP production in sensory neurons, we hypothesized that stress-induced gastric mucosal injury occurs less in females than in males. Gastric ulcer index (UI), gastric myeloperoxidase (MPO) activity, gastric tissue levels of CGRP and 6-keto-PGF1α, a stable metabolite of PGI2, were determined in male and female wild-type (CGRP+/+) mice, CGRP knockout (CGRP-/-) mice and Wistar rats subjected to stress. Results : UI and MPO activities were lower and gastric tissue levels of 6-keto-PGF1α were higher in females than in males in CGRP+/+ mice, while there were no such gender differences in CGRP-/- mice. Gastric tissue levels of CGRP in rats were significantly higher in females than in males. Gender differences seen in CGRP+/+ mice were also observed in rats, but they were eliminated by pretreatment with capsazepine (CPZ), a vanilloid receptor antagonist, and by ovariectomy (OVX) in female rats. Reversal of gender differences by OVX was not observed in estradiol-treated female rats. Levels of CGRP mRNA in dorsal root ganglion neurons isolated from female rats were decreased by OVX and these decreases were reversed by estradiol replacement. in conclusions, estrogen-mediated increases in CGRP levels in sensory neurons might contribute to reduce stress-induced gastric mucosal injury by attenuating inflammatory responses. This might at least partly explain the gender difference observed in the development of stress-induced gastric mucosal injury in rodents.

感觉神经元通过增加胃粘膜前列环素（PGI2）水平释放降钙素基因相关肽（CGRP），在减轻应激性胃粘膜损伤中起关键作用。由于雌激素增强了感觉神经元中神经生长因子介导的CGRP的产生，我们假设应激性胃粘膜损伤在女性中的发生率低于男性。测定应激条件下雄性、雌性野生型（CGRP+/+）小鼠、CGRP敲除型（CGRP-/-）小鼠和Wistar大鼠的胃溃疡指数（UI）、胃髓过氧化物酶（MPO）活性、胃组织中CGRP和PGI2稳定代谢产物6-酮- pgf1 α水平。结果：CGRP+/+小鼠胃组织中6-酮- pgf1 α在雌性比雄性高，UI和MPO活性较低，而CGRP-/-小鼠则无性别差异。雌性大鼠胃组织CGRP水平明显高于雄性大鼠。在大鼠中也观察到CGRP+/+小鼠的性别差异，但通过辣椒素（一种香草受体拮抗剂）预处理和雌性大鼠卵巢切除术（OVX）消除了这种差异。在雌二醇处理的雌性大鼠中未观察到OVX对性别差异的逆转。雌性大鼠背根神经节神经元CGRP mRNA水平在OVX作用下下降，雌二醇替代可逆转这种下降。综上所述，雌激素介导的感觉神经元CGRP水平升高可能通过减轻炎症反应来减轻应激性胃粘膜损伤。这至少可以部分解释啮齿动物应激性胃粘膜损伤发生过程中观察到的性别差异。

项目成果

期刊论文数量（44）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Inhibition of lipopolysaccharide-induced tissue factor expression in monocytes by urinary trypsin inhibitor in vitro and in vivo.

体外和体内尿胰蛋白酶抑制剂抑制单核细胞中脂多糖诱导的组织因子表达。

DOI：
发表时间：
2005
期刊：
Thromb Haemost 94
影响因子：
0
作者：
Hidaka S;Kawamoto M;Kurita S;Yuge O.;Kurata M;Harada N;Harada N;Harada N;Okajima K;Kitamura T;Okajima K;Harada. N;Molor-Erdene P;Okajima K;Molor-Erdene P
通讯作者：
Molor-Erdene P

Antithrombin reduces ischemia/reperfusion-induced liver injury in rats by activation of cyclooxygenase-1.

抗凝血酶通过激活 cyclooxygenase-1 减少大鼠缺血/再灌注引起的肝损伤。