Gao Yihuai, Zhou Shufeng, Wen Jianbo, Huang Min, Xu Anlong
New Zealand Institute of Natural Medicines, Auckland, New Zealand.
Life Sci. 2002 Dec 27;72(6):731-45. doi: 10.1016/s0024-3205(02)02301-9.
Many cytokines, in particular tumor necrosis factor (TNF)-alpha have been known to play an important role in the pathogenesis of gastric mucosal lesions caused by various factors such as drugs and Helicobacter pylori infection. Our previous studies have shown that the polysaccharide fractions isolated from the fruiting bodies of Ganoderma lucidum (GLPS) prevented indomethacin- and acetic acid-induced gastric mucosal lesions in the rat. However, the mechanisms remain unclear. This study aimed to investigate whether GLPS had a direct mucosal healing effect in the indomethacin-treated rat, and to explore the possible mechanisms by determining the gastric mucosal mRNA and protein levels of TNF-alpha and ornithine decarboxylase (ODC) activity. In addition, the effects of GLPS on the cellular proliferation, ODC and c-Myc protein expression and mucus synthesis in the rat gastric cell culture (RGM-1) were examined. The present study demonstrated that GLPS at 250 and 500 mg/kg by intragastric input caused ulcer-healing effect in the rat; this was accompanied with a significant suppression of TNF-alpha gene expression, but with an increased ODC activity. In RGM-1 cells, GLPS at 0.05, 0.25 and 1.0 mg/ml significantly enhanced [3H]thymidine incorporation and ODC activity in a concentration-dependent manner. However, these effects were abrogated by the addition of the ODC inhibitor, DL-alpha-difluoromethyl-ornithine (DFMO). GLPS at 0.25-1.0 mg/ml also increased mucus synthesis, as indicated by the increased D-[6-3H]glucosamine incorporation in RGM-1 cells. Furthermore, GLPS at 0.05-1.0 mg/ml increased the c-Myc protein expression. These findings indicated that GLPS produced a mucosal healing effect in the rat model, perhaps due partly to the suppression of TNF-alpha and induction of c-myc and ODC gene.
许多细胞因子，尤其是肿瘤坏死因子（TNF）-α，在由药物和幽门螺杆菌感染等各种因素引起的胃黏膜病变发病机制中发挥重要作用。我们之前的研究表明，从灵芝子实体中分离得到的多糖组分（GLPS）可预防吲哚美辛和乙酸诱导的大鼠胃黏膜损伤。然而，其机制仍不清楚。本研究旨在探讨GLPS对吲哚美辛处理的大鼠是否具有直接的黏膜愈合作用，并通过测定胃黏膜TNF-α的mRNA和蛋白水平以及鸟氨酸脱羧酶（ODC）活性来探索可能的机制。此外，还研究了GLPS对大鼠胃细胞培养物（RGM-1）中细胞增殖、ODC和c-Myc蛋白表达以及黏液合成的影响。本研究表明，经胃内给予250和500 mg/kg的GLPS可使大鼠产生溃疡愈合作用；这伴随着TNF-α基因表达的显著抑制，但ODC活性增加。在RGM-1细胞中，0.05、0.25和1.0 mg/ml的GLPS以浓度依赖的方式显著增强[3H]胸腺嘧啶核苷掺入和ODC活性。然而，添加ODC抑制剂DL-α-二氟甲基鸟氨酸（DFMO）可消除这些作用。0.25 - 1.0 mg/ml的GLPS也增加了黏液合成，RGM-1细胞中D-[6-3H]葡萄糖胺掺入增加表明了这一点。此外，0.05 - 1.0 mg/ml的GLPS增加了c-Myc蛋白表达。这些发现表明，GLPS在大鼠模型中产生了黏膜愈合作用，这可能部分归因于对TNF-α的抑制以及c-myc和ODC基因的诱导。
