Ohkawara Tatsuya, Nishihira Jun, Takeda Hiroshi, Miyashita Kencho, Kato Kanji, Kato Mototsugu, Sugiyama Toshiro, Asaka Masahiro
Department of Gastroenterology and Hematology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Scand J Gastroenterol. 2005 Sep;40(9):1049-57. doi: 10.1080/00365520510023161.
Geranylgeranylacetone (GGA) has recently been reported to induce heat shock protein (HSP) 70, which has a protective function against inflammation. We investigated the therapeutic effects of oral administration of GGA on dextran sulfate sodium (DSS)-induced colitis in mice.
BALB/c mice were given 3% DSS solution orally for 7 days to induce colitis. The disease activity of colitis was assessed clinically every day, and histology in the colon was evaluated at 7 days post-DSS. The levels of myeloperoxidase (MPO) activity, tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma in the colon tissues were also examined. In addition, expression of HSPs 25, 40, 70 and 90 in the colon tissue was determined by Western blot analysis. Mice were orally administered GGA (50-500 mg/kg) when treatment of DSS started.
It was found that GGA significantly reduced the clinical severity of colitis and suppressed the levels of MPO activity, TNF-alpha and IFN-gamma induced by DSS in the colon. On the other hand, GGA enhanced the expression of HSP70 in the colon of mice given DSS.
Taken together, these results suggest that GGA is a new anti-inflammatory drug that could be useful in the treatment of colitis such as inflammatory bowel disease.
最近有报道称香叶基香叶基丙酮（GGA）可诱导具有抗炎保护功能的热休克蛋白（HSP）70。我们研究了口服GGA对葡聚糖硫酸钠（DSS）诱导的小鼠结肠炎的治疗作用。
给BALB/c小鼠口服3% DSS溶液7天以诱导结肠炎。每天临床评估结肠炎的疾病活动情况，并在给予DSS后7天评估结肠组织学。还检测了结肠组织中髓过氧化物酶（MPO）活性、肿瘤坏死因子（TNF）-α和干扰素（IFN）-γ的水平。此外，通过蛋白质印迹分析测定结肠组织中HSPs 25、40、70和90的表达。当开始用DSS治疗时，给小鼠口服GGA（50 - 500 mg/kg）。
发现GGA显著降低了结肠炎的临床严重程度，并抑制了DSS诱导的结肠中MPO活性、TNF-α和IFN-γ的水平。另一方面，GGA增强了给予DSS的小鼠结肠中HSP70的表达。
综上所述，这些结果表明GGA是一种新型抗炎药物，可能对治疗诸如炎症性肠病等结肠炎有用。
