Mechanism of the antiulcerogenic effect of Ganoderma lucidum polysaccharides on indomethacin-induced lesions in the rat
Mechanism of the antiulcerogenic effect of Ganoderma lucidum polysaccharides on indomethacin-induced lesions in the rat
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DOI：
10.1016/s0024-3205(02)02301-9
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发表时间：
2002-12-27
期刊：
影响因子：
6.1
通讯作者：
Xu, AL
中科院分区：
文献类型：
--
作者：
Gao, YH;Zhou, SF;Xu, AL
已知许多细胞因子，特别是肿瘤坏死因子（TNF）-α在由各种因素如药物和幽门螺杆菌感染引起的胃粘膜病变的发病机制中起重要作用。我们以前的研究表明，从灵芝子实体（GLPS）分离的多糖组分防止消炎痛和乙酸诱导的大鼠胃粘膜病变。然而，其机制仍不清楚。本研究旨在探讨GLPS是否对消炎痛治疗的大鼠具有直接的粘膜愈合作用，并通过测定胃粘膜TNF-α的mRNA和蛋白水平以及鸟氨酸脱羧酶（ODC）活性来探讨其可能的机制。此外，还观察了GLPS对大鼠胃细胞（RGM-1）增殖、ODC和c-Myc蛋白表达及粘液合成的影响。本研究表明，GLPS在250和500 mg/kg的胃内输入引起大鼠溃疡愈合的影响，这是伴随着TNF-α基因表达的显着抑制，但与ODC活性增加。0.05、0.25和1.0mg/ml的GLPS浓度依赖性地促进RGM-1细胞[3 H]胸腺嘧啶核苷掺入和ODC活性。然而，这些作用通过添加ODC抑制剂DL-α-二氟甲基-鸟氨酸（DFMO）而消除。0.25 - 1.0 mg/ ml的GLPS还增加粘液合成，正如RGM-1细胞中D-[6-H-3]葡萄糖胺掺入增加所表明的那样。0.05- 1.0mg/ml的GLPS可促进c-Myc蛋白的表达。这些结果表明，GLPS在大鼠模型中产生粘膜愈合作用，可能部分归因于TNF-α的抑制和c-myc和ODC基因的诱导。(C)2002年爱思唯尔科技有限公司All rights reserved.
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 [3 H]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-H-3]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. (C) 2002 Elsevier Science Inc. All rights reserved.