Chauhan Anil Kumar, Kang Sun Chul
Department of Biotechnology, Daegu University, Kyoungsan, Kyoungbook 712-714, Republic of Korea.
Department of Biotechnology, Daegu University, Kyoungsan, Kyoungbook 712-714, Republic of Korea.
Alcohol. 2015 Nov;49(7):739-45. doi: 10.1016/j.alcohol.2015.08.004. Epub 2015 Oct 20.
In this study, we investigated the potential of thymol and its mode of action to protect against the gastric mucosal injury induced by ethanol consumption in an in vivo model. Moreover, we determined the role of thymol in regulation of matrix metalloproteinase-9 (MMP-9), an enzyme belonging to the metalloproteinase group, which is responsible for the remodeling of injured tissues. Sprague-Dawley rats pretreated with thymol (10 mg/kg body weight) or normal saline were subjected to intragastric administration of 95% ethanol (5 mL/kg body weight). Morphological examination included ulcer index as a measurement of hemorrhages, and hematoxylin and eosin (H&E) staining was performed to analyze severity of gastric mucosal damage. Gelatinase zymography of tissue extract and in situ zymography were performed to demonstrate MMP-9 activity. Results of macroscopic examination suggested that thymol significantly protected gastric mucosa from damage induced by alcohol, which was severe in the case of alcohol-only treatment. H&E data demonstrated necrosis of the corpus region in alcohol-treated rats, which was abrogated in rats pretreated with thymol. Further, thymol protected against the constriction of small arteries and neutrophil infiltration in lymphatic vessels. Expression of antioxidant enzymes increased in the thymol-pretreated group, and downregulation of MMP-9 protein expression was observed by gelatin zymography as well as in situ zymography. The results of this study suggest that thymol protects against gastric mucosa injury induced by ethanol consumption by upregulating the secretion of antioxidant enzymes and downregulating the expression of the MMP-9 protein.
在本研究中,我们在体内模型中探究了百里香酚预防乙醇所致胃黏膜损伤的潜力及其作用机制。此外,我们还确定了百里香酚在调节基质金属蛋白酶-9(MMP-9)中的作用,MMP-9是金属蛋白酶家族的一种酶,负责损伤组织的重塑。用百里香酚(10毫克/千克体重)或生理盐水预处理的Sprague-Dawley大鼠接受95%乙醇(5毫升/千克体重)灌胃。形态学检查包括以溃疡指数衡量出血情况,并进行苏木精和伊红(H&E)染色以分析胃黏膜损伤的严重程度。对组织提取物进行明胶酶谱分析和原位酶谱分析以显示MMP-9活性。大体检查结果表明,百里香酚能显著保护胃黏膜免受酒精所致损伤,仅用酒精处理时损伤严重。H&E数据显示,酒精处理的大鼠胃体部出现坏死,而用百里香酚预处理的大鼠则未出现。此外,百里香酚可防止小动脉收缩和淋巴管中的中性粒细胞浸润。抗氧化酶的表达在百里香酚预处理组中增加,通过明胶酶谱分析和原位酶谱分析均观察到MMP-9蛋白表达下调。本研究结果表明,百里香酚通过上调抗氧化酶的分泌和下调MMP-9蛋白的表达来预防乙醇所致胃黏膜损伤。