肠易激综合征患者及三硝基苯磺酸诱导的结肠炎大鼠中血管活性肠肽表达的改变
Altered vasoactive intestinal peptides expression in irritable bowel syndrome patients and rats with trinitrobenzene sulfonic acid-induced colitis.
作者信息
Del Valle-Pinero Arseima Y, Sherwin LeeAnne B, Anderson Ethan M, Caudle Robert M, Henderson Wendy A
机构信息
Arseima Y Del Valle-Pinero, LeeAnne B Sherwin, Wendy A Henderson, Digestive Disorders Unit, Biobehavioral Branch, Division of Intramural Research, National Institute of Nursing Research, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, United States.
出版信息
World J Gastroenterol. 2015 Jan 7;21(1):155-63. doi: 10.3748/wjg.v21.i1.155.
AIM
To investigate the vasoactive intestinal peptides (VIP) expression in irritable bowel syndrome (IBS) and trinitrobenzene sulfonic acid (TNBS) induced colitis.
METHODS
The VIP gene expression and protein plasma levels were measured in adult participants (45.8% male) who met Rome III criteria for IBS for longer than 6 mo and in a rat model of colitis as induced by TNBS. Plasma and colons were collected from naïve and inflamed rats. Markers assessing inflammation (i.e., weight changes and myeloperoxidase levels) were assessed on days 2, 7, 14 and 28 and compared to controls. Visceral hypersensitivity of the rats was assessed with colo-rectal distension and mechanical threshold testing on hind paws. IBS patients (n = 12) were age, gender, race, and BMI-matched with healthy controls (n = 12). Peripheral whole blood and plasma from fasting participants was collected and VIP plasma levels were assayed using a VIP peptide-enzyme immunoassay. Human gene expression of VIP was analyzed using a custom PCR array.
RESULTS
TNBS induced colitis in the rats was confirmed with weight loss (13.7 ± 3.2 g) and increased myeloperoxidase activity. Visceral hypersensitivity to colo-rectal distension was increased in TNBS treated rats up to 21 d and resolved by day 28. Somatic hypersensitivity was also increased up to 14 d post TNBS induction of colitis. The expression of an inflammatory marker myeloperoxidase was significantly elevated in the intracellular granules of neutrophils in rat models following TNBS treatment compared to naïve rats. This confirmed the induction of inflammation in rats following TNBS treatment. VIP plasma concentration was significantly increased in rats following TNBS treatment as compared to naïve animals (P < 0.05). Likewise, the VIP gene expression from peripheral whole blood was significantly upregulated by 2.91-fold in IBS patients when compared to controls (P < 0.00001; 95%CI). VIP plasma protein was not significantly different when compared with controls (P = 0.193).
CONCLUSION
Alterations in VIP expression may play a role in IBS. Therefore, a better understanding of the physiology of VIP could lead to new therapeutics.
目的
研究血管活性肠肽（VIP）在肠易激综合征（IBS）及三硝基苯磺酸（TNBS）诱导的结肠炎中的表达情况。
方法
对符合罗马III标准且IBS病程超过6个月的成年参与者（男性占45.8%）以及TNBS诱导的结肠炎大鼠模型，检测其VIP基因表达及血浆蛋白水平。从未处理和炎症状态的大鼠采集血浆和结肠组织。在第2、7、14和28天评估评估炎症的指标（即体重变化和髓过氧化物酶水平），并与对照组比较。通过直肠扩张和后爪机械阈值测试评估大鼠的内脏超敏反应。IBS患者（n = 12）在年龄、性别、种族和体重指数方面与健康对照者（n = 12）相匹配。采集空腹参与者的外周全血和血浆，采用VIP肽酶免疫分析法检测血浆中VIP水平。使用定制的PCR阵列分析VIP的人类基因表达。
结果
TNBS诱导的大鼠结肠炎表现为体重减轻（13.7 ± 3.2 g）和髓过氧化物酶活性增加，得以证实。TNBS处理的大鼠对直肠扩张的内脏超敏反应在21天内增强，至第28天恢复。在TNBS诱导结肠炎后14天内，躯体超敏反应也增强。与未处理的大鼠相比，TNBS处理后的大鼠模型中，中性粒细胞胞内颗粒中炎症标志物髓过氧化物酶的表达显著升高。这证实了TNBS处理后大鼠炎症的诱导。与未处理的动物相比，TNBS处理后的大鼠血浆中VIP浓度显著升高（P < 0.05）。同样，与对照组相比，IBS患者外周全血中VIP基因表达显著上调2.91倍（P < 0.00001；95%CI）。与对照组相比，VIP血浆蛋白无显著差异（P = 0.193）。
结论
VIP表达的改变可能在IBS中起作用。因此，更好地了解VIP的生理学特性可能会带来新的治疗方法。
Zotero 插件