沒食子酸丙酯對indomethacin誘導Wistar大鼠胃黏膜損傷之保護作用

胃黏膜損傷為常見的疾病之一，而造成胃黏膜損傷的危險因子有藥物、過量飲酒、吸煙和壓力等，上述因子使胃黏膜發炎並破壞黏膜完整性。Indomethacin為常見的非類固醇消炎止痛藥 (non-steroidal anti-inflammatory drugs, NSAIDs)，其通過抑制環氧化酶活性達到消炎、鎮痛之效果，但同時也會抑制黏膜增生，導致胃酸及其他因子直接侵蝕胃黏膜。沒食子酸丙酯 (propyl gallate, PG) 屬於酚類化合物家族，具有優良的抗氧化和抗發炎特性，被廣泛用於食品添加劑中。本研究旨在探討PG對indomethacin誘導大鼠產生的胃黏膜損傷是否具保護作用。此實驗以6週齡雄性Wistar大鼠作為實驗動物，將其分為6組：(1) 控制組 (C)；(2) vehicle組 (vehicle)；(3) 低劑量PG組 (20 mg/kg PG, LPG)；(4) 中劑量PG組 (40 mg/kg PG, MPG)；(5) 高劑量PG組 (100 mg/kg PG, HPG)；(6) 正控藥物組 (30 mg/kg omeprazole, OM)。實驗為期7天，第2至6組於第7天管餵100 mg/kg的indomethacin，並在6小時之後進行犧牲，採集血液與臟器樣本後，進行後續相關分析。由結果可觀察到，vehicle組的大鼠胃黏膜有顯著性的潰瘍發生，其潰瘍面積達21.90±3.52 mm2。而PG與OM處理組的潰瘍面積皆有下降之趨勢，分別為LPG：7.46±0.59 mm2、MPG：6.28±0.81 mm2、HPG：1.85±0.24 mm2及OM：0.14±0.07 mm2。發炎路徑相關蛋白之分析結果顯示，vehicle組大鼠胃黏膜組織的NF-κB、COX-2、TNF-α、IL-6和iNOS蛋白表現皆顯著高於控制組的大鼠 (p<0.05)，而給予PG預處理可顯著性降低發炎相關蛋白的表現 (p<0.05)。除此之外，PG的給予也能顯著提升胃黏膜中前列腺素E2 (prostaglandin E2, PGE2) 的含量 (p<0.05)。在抗氧化物質方面，vehicle組的GSH含量在與控制組相比之下呈現顯著性的下降 (p<0.05)，而PG的處理可顯著的提高GSH的含量 (p<0.05)；而在SOD活性分析的結果中，vehicle組與控制組相比SOD活性呈下降之趨勢，且具顯著性差異 (p<0.05)，而PG預處理可顯著性提高SOD的活性 (p<0.05)；CAT活性分析中則顯示，vehicle組具有較高之活性，PG的處理可以讓大鼠胃黏膜CAT活性回復至相似於控制組的數值。綜合上述的結果，PG可藉由其抗氧化及抗發炎的特性，達到減緩indomethacin所誘導的胃黏膜損傷之保護效果。

關鍵字

胃黏膜損傷； Indomethacin ；沒食子酸丙酯；抗氧化酵素

並列摘要

Gastric mucosal damage is one of the common diseases, and the main risk factors for gastric mucosal damage include drugs, excessive drinking, smoking and stress. These factors cause gastric mucosal inflammation and destroy the integrity of the mucosa. Indomethacin is a kind of common non-steroidal anti-inflammatory drugs (NASIDs), which achieves anti-inflammatory and analgesic effects by inhibiting cyclooxygenase activity, but it also inhibits proliferation of mucosal cells, causing gastric mucosal erosion directly caused by gastric acid and other factors. Propyl gallate (PG) belongs to the family of phenolic compounds and is widely used in food additives due to its excellent antioxidant and anti-inflammatory properties. This study was aimed to investigate whether PG has a protective effect on indomethacin-induced gastric mucosal injury in rats. In this experiment, 6-week-old male Wistar rats were used as experimental animals, and they were divided into 6 groups: (1) control group (C); (2) vehicle group (vehicle); (3) low dose PG group (20 mg/kg of PG, LPG); (4) medium dose PG group (40 mg/kg of PG, MPG); (5) high dose PG group (100 mg/kg of PG, HPG); (4) positive control group (30 mg/kg of omeprazole, OM). The experimental period is 7 days, and the rats in groups 2 to 6 were orally fed with 100 mg/kg of indomethacin at day 7. All rats were then sacrificed 6 hours later, and the blood and organ samples were collected for further analysis. It can be observed from the results that significant ulcers occurred in the gastric mucosa of rats in the vehicle group, with an ulcer area of 21.90±3.52 mm2. The gastric mucosal ulcer area of rats in the PG and OM treatment groups had a tendency to decrease and their ulcer area were LPG: 7.46±0.59 mm2, MPG: 6.28±0.81 mm2, HPG: 1.85±0.24 mm2, and OM: 0.14±0.07 mm2. Results of protein analysis related to inflammation pathways showed that the expressions of NF-κB, COX-2, TNF-α, IL-6 and iNOS in the gastric mucosal tissue of rats in the vehicle group were significantly higher than those in the control group (p<0.05), while pretreatment with PG significantly reduced the expression of inflammation-related proteins (p<0.05). Moreover, the administration of PG also significantly increased the content of prostaglandin E2 (PGE2) in the gastric mucosa of rats. In terms of antioxidant system, the GSH content of the vehicle group showed a significant decrease compared with the control group (p<0.05), while the treatment of PG significantly enhanced the GSH content (p<0.05). The results of superoxide dismutase (SOD) activity analysis, the vehicle group showed a decreasing trend of SOD activity compared with the control group, and there was a significant difference (p<0.05), while PG pretreatment can significantly increase the SOD activity (p<0.05). Catalase (CAT) activity analysis showed that the CAT of gastric mucosa of vehicle group had a higher activity, while treatment of PG can restore the CAT activity of the rats to a value similar to that of the control group. According to the above results, PG can achieve the protective effects on alleviation of the gastric mucosal damage induced by indomethacin through its anti-oxidant and anti-inflammatory properties.

並列關鍵字

Gastric mucosal injury ； Indomethacin ； Propyl gallate ； Antioxidant enzyme

參考文獻

Abdel-Tawab, M. S., O. Mostafa Tork, G. Mostafa-Hedeab, M. Ewaiss Hassan, and D. Azmy Elberry. 2020. Protective effects of quercetin and melatonin on indomethacin Induced Gastric Ulcers in Rats. Reports of biochemistry & molecular biology. 9(3): 278-290.

Google Scholar

AlKreathy, H. M., M. K. Alghamdi, and A. Esmat. 2020. Tetramethylpyrazine ameliorates indomethacin-induced gastric ulcer in rats: Impact on oxidative, inflammatory, and angiogenic machineries. Saudi Pharm J. 28(8): 916-926.

Google Scholar

Athaydes, B. R., G. M. Alves, A. Assis, J. V. D. Gomes, R. P. Rodrigues, B. P. Campagnaro, B. V. Nogueira, D. Silveira, R. M. Kuster, T. M. C. Pereira, R. R. Kitagawa, and R. C. R. Gonçalves. 2019. Avocado seeds (Persea americana Mill.) prevents indomethacin-induced gastric ulcer in mice. Food Res Int. 119: 751-760.

Google Scholar

Bampidis, V., G. Azimonti, M. de Lourdes Bastos, H. Christensen, B. Dusemund, M. Kos Durjava, M. Kouba, M. López-Alonso, S. López Puente, F. Marcon, B. Mayo, A. Pechová, M. Petkova, F. Ramos, Y. Sanz, R. E. Villa, R. Woutersen, G. Aquilina, G. Bories, J. Gropp, C. Nebbia, and M. L. Innocenti. 2020. Safety and efficacy of propyl gallate for all animal species. Efsa j. 18(4): e06069.

Google Scholar

Baumgartner, H. K., and M. H. Montrose. 2004. Regulated alkali secretion acts in tandem with unstirred layers to regulate mouse gastric surface pH. Gastroenterology. 126(3): 774-783.

Google Scholar

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