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阿片耐药的系统内调节机制
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作者 刘晓艳(综述) 孙莉(审校) 《麻醉与监护论坛》 2008年第1期34-36,共3页
疼痛治疗目前仍主要依赖阿片药物,但阿片药物的耐药性给病人增加了极大的痛苦,严重影响了阿片药物的应用。目前的研究结果表明,阿片耐药的产生分为系统内和系统间两种机制。本文仅从阿片受体的系统内调节的角度,对阿片耐药的机制进... 疼痛治疗目前仍主要依赖阿片药物,但阿片药物的耐药性给病人增加了极大的痛苦,严重影响了阿片药物的应用。目前的研究结果表明,阿片耐药的产生分为系统内和系统间两种机制。本文仅从阿片受体的系统内调节的角度,对阿片耐药的机制进行阐述,总结系统内调节机制的研究进展和热点问题。 展开更多
关键词 阿片药物 受体耐药 系统内调节
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Role of nuclear receptor NR4A2 in gastrointestinal inflammation and cancers 被引量:7
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作者 Yi-Fang Han Guang-Wen Cao 《World Journal of Gastroenterology》 SCIE CAS CSCD 2012年第47期6865-6873,共9页
NR4A2 is a transcription factor belonging to the steroid orphan nuclear receptor superfamily.It was originally considered to be essential in the generation and maintenance of dopaminergic neurons,and associated with n... NR4A2 is a transcription factor belonging to the steroid orphan nuclear receptor superfamily.It was originally considered to be essential in the generation and maintenance of dopaminergic neurons,and associated with neurological disorders such as Parkinson's disease.Recently,NR4A2 has been found to play a critical role in some inflammatory diseases and cancer.NR4A2 can be efficiently trans-activated by some proinflammatory cytokines,such as tumor necrosis factor-α,interleukin-1β,and vascular endothelial growth factor(VEGF).The nuclear factor-κB signaling pathway serves as a principal regulator of inducible NR4A expression in immune cells.NR4A2 can trans-activate Foxp3,a hallmark specifically expressed in regulatory T(Treg) cells,and plays a critical role in the differentiation,maintenance,and function of Treg cells.NR4A2 in T lymphocytes is pivotal for Treg cell induction and suppression of aberrant induction of Th1 under physiological and pathological conditions.High density of Foxp3 + Treg cells is significantly associated with gastrointestinal inflammation,tumor immune escape,and disease progression.NR4A2 is produced at high levels in CD133 + colorectal carcinoma(CRC) cells and significantly upregulated by cyclooxygenase-2-derived prostaglandin E 2 in a cyclic adenosine monophosphate(cAMP)/protein kinase A(PKA)-dependent manner in CRC cells.The cAMP/PKA signaling pathway is the common pathway of NR4A2-related inflammation and cancer.NR4A2 trans-activates osteopontin,a direct target of the Wnt/β-catenin pathway associated with CRC invasion,metastasis,and poor prognosis.Knockdown of endogenous NR4A2 expression attenuates VEGF-induced endothelial cell proliferation,migration and in vivo angiogenesis.Taken together,NR4A2 emerges as an important nuclear factor linking gastrointestinal inflammation and cancer,especially CRC,and should serve as a candidate therapeutic target for inflammation-related gastrointestinal cancer. 展开更多
关键词 NR4A2 INFLAMMATION Immune cells Signaling pathway Gastrointestinal carcinoma
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