Targeted deletion of neuropeptide Y (NPY) modulates experimental colitis.
Targeted deletion of neuropeptide Y (NPY) modulates experimental colitis.
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DOI：
10.1371/journal.pone.0003304
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发表时间：
2008-10-01
期刊：
影响因子：
3.7
通讯作者：
Srinivasan S
中科院分区：
文献类型：
--
作者：
Chandrasekharan B;Bala V;Kolachala VL;Vijay-Kumar M;Jones D;Gewirtz AT;Sitaraman SV;Srinivasan S
神经源性炎症在炎症性肠病（IBD）的发病机制中起着重要作用。我们研究了神经肽Y （NPY）和神经元一氧化氮合酶（nNOS）在调节结肠炎中的作用。用葡聚糖硫酸钠（3% DSS）或链霉素预处理鼠伤寒沙门菌（S.T.）诱导野生型（WT）和NPY （NPY−/−）基因敲除小鼠结肠炎。结肠炎通过临床评分、组织学评分和髓过氧化物酶活性进行评估。免疫染色法检测NPY和nNOS的表达。通过测量过氧化氢酶活性、谷胱甘肽和亚硝酸盐水平来评估氧化应激。用等长肌肉记录法测定WT和dss处理小鼠的结肠运动。DSS / s.t。诱导WT小鼠肠神经元NPY和nNOS表达增加。与NPY - / -相比，WT小鼠更容易发生炎症，这可以从更高的临床和组织学评分以及髓过氧化物酶（MPO）活性（p<0.01）中看出。DSS-WT小鼠亚硝酸盐增加，谷胱甘肽（GSH）水平降低，过氧化氢酶活性增加，表明氧化应激加重。s.t.t治疗的nNOS - / -和NPY- / - /nNOS - / -小鼠的组织学评分、MPO和趋化因子KC较低，支持了NPY诱导的nNOS减轻炎症的发现。炎症导致DSS-WT小鼠结肠运动功能的慢性损害。NPY处理的大鼠肠神经元体外亚硝酸盐和TNF-α的产生增加。NPY介导的nNOS增加是氧化应激和随后的炎症的决定因素。我们的研究强调了神经元NPY和nNOS作为IBD炎症过程介质的作用。
Neurogenic inflammation plays a major role in the pathogenesis of inflammatory bowel disease (IBD). We examined the role of neuropeptide Y (NPY) and neuronal nitric oxide synthase (nNOS) in modulating colitis. Colitis was induced by administration of dextran sodium sulphate (3% DSS) or streptomycin pre-treated Salmonella typhimurium (S.T.) in wild type (WT) and NPY (NPY−/−) knockout mice. Colitis was assessed by clinical score, histological score and myeloperoxidase activity. NPY and nNOS expression was assessed by immunostaining. Oxidative stress was assessed by measuring catalase activity, glutathione and nitrite levels. Colonic motility was assessed by isometric muscle recording in WT and DSS-treated mice. DSS/S.T. induced an increase in enteric neuronal NPY and nNOS expression in WT mice. WT mice were more susceptible to inflammation compared to NPY−/− as indicated by higher clinical & histological scores, and myeloperoxidase (MPO) activity (p<0.01). DSS-WT mice had increased nitrite, decreased glutathione (GSH) levels and increased catalase activity indicating more oxidative stress. The lower histological scores, MPO and chemokine KC in S.T.-treated nNOS−/− and NPY−/−/nNOS−/− mice supported the finding that loss of NPY-induced nNOS attenuated inflammation. The inflammation resulted in chronic impairment of colonic motility in DSS-WT mice. NPY –treated rat enteric neurons in vitro exhibited increased nitrite and TNF-α production. NPY mediated increase in nNOS is a determinant of oxidative stress and subsequent inflammation. Our study highlights the role of neuronal NPY and nNOS as mediators of inflammatory processes in IBD.
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影响因子：
3.1
作者：
Gaudio, E;Taddei, G;Caprilli, R
通讯作者：
Caprilli, R
影响因子：
3.1
作者：
Barthel, M;Hapfelmeier, S;Hardt, WD
通讯作者：
Hardt, WD
影响因子：
15.9
作者：
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通讯作者：
Srinivasan, S
DOI：
10.1152/ajpgi.1995.268.4.g673
发表时间：
1995-04-01
影响因子：
4.5
作者：
HOGABOAM, CM;JACOBSON, K;BLENNERHASSETT, MG
通讯作者：
BLENNERHASSETT, MG
DOI：
10.1016/s0169-328x(03)00131-1
发表时间：
2003-05-26
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Li, Q;Goodchild, AK;Pilowsky, PM
通讯作者：
Pilowsky, PM