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辛伐他汀可减轻三硝基苯磺酸诱导的结肠炎,但对恶唑酮诱导的结肠炎无效。

Simvastatin attenuates trinitrobenzene sulfonic acid-induced colitis, but not oxazalone-induced colitis.

作者信息

Ikeda Maho, Takeshima Fuminao, Isomoto Hajime, Shikuwa Saburo, Mizuta Yohei, Ozono Yoshiyuki, Kohno Shigeru

机构信息

Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.

出版信息

Dig Dis Sci. 2008 Jul;53(7):1869-75. doi: 10.1007/s10620-007-0102-0. Epub 2007 Dec 1.

Abstract

PURPOSE

To determine whether simvastatin is able to inhibit inflammation in trinitrobenzene sulfonic acid (TNBS)-induced or oxazalone (OXA)-induced colitis.

RESULTS

In the prophylactic protocol, simvastatin dose-dependently suppressed the decrease in body weight and inflammatory grade of TNBS-treated mice. In contrast, in the therapeutic protocol, no significant difference in body weight reduction was observed between simvastatin-treated and control mice. IFN-gamma release from LP cells was significantly suppressed in mice receiving high-dose simvastatin in the prophylactic protocol. In contrast to TNBS colitis, even high-dose prophylactic simvastatin had no suppressive effects on either weight reduction or the inflammatory grade in OXA colitis.

CONCLUSION

Our results indicate that simvastatin negatively regulates inflammation in TNBS-induced colitis, but not in OXA-induced colitis. In TNBS-induced colitis, simvastatin suppressed the Th1-polarized immune response. Our findings suggest that simvastatin has potential effects as a therapeutic agent in human inflammatory bowel disease, particularly Crohn's disease.

摘要

目的

确定辛伐他汀是否能够抑制三硝基苯磺酸(TNBS)诱导或恶唑酮(OXA)诱导的结肠炎中的炎症。

结果

在预防性方案中,辛伐他汀剂量依赖性地抑制了TNBS处理小鼠体重的下降和炎症分级。相比之下,在治疗性方案中,辛伐他汀处理的小鼠和对照小鼠之间在体重减轻方面未观察到显著差异。在预防性方案中,接受高剂量辛伐他汀的小鼠中,LP细胞释放的IFN-γ明显受到抑制。与TNBS结肠炎相反,即使是高剂量预防性辛伐他汀对OXA结肠炎的体重减轻或炎症分级也没有抑制作用。

结论

我们的结果表明,辛伐他汀对TNBS诱导的结肠炎中的炎症起负调节作用,但对OXA诱导的结肠炎无效。在TNBS诱导的结肠炎中,辛伐他汀抑制了Th1极化的免疫反应。我们的研究结果表明,辛伐他汀作为一种治疗药物在人类炎症性肠病,特别是克罗恩病中具有潜在作用。

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