Small Intestine Protection of Mica Against Non-Steroidal Anti-Inflammatory Drugs-Injury Through ERK1/2 Signal Pathway in Rats

Small Intestine Protection of Mica Against Non-Steroidal Anti-Inflammatory Drugs-Injury Through ERK1/2 Signal Pathway in Rats
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云母通过 ERK1/2 信号通路保护大鼠小肠免受非甾体抗炎药物损伤

DOI:
10.3389/fphar.2019.00871
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发表时间:
2019-08
期刊:
Front Pharmacol
影响因子:
--
通讯作者:
Zhengyu Fang
Zhengyu Fang
中科院分区:
其他
文献类型:
--
作者:
Shuo Zhang;Yinghua He;Zheng Shi;Jianping Jiang;Beihui He;Sumei Xu;Zhengyu Fang

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目的:非甾体类抗炎药(NSAIDs)对小肠的损伤作用是众所周知的。云母是一种天然粘土,在我国已广泛用于治疗胃病。但云母在小肠损伤中的作用及机制尚不清楚。本研究旨在阐明云母对双氯芬酸所致大鼠肠损伤的影响。研究方法:将大鼠随机分为对照组、模型组、PAR-2激动剂组(SLIGRL-NH 2组)、对照肽组(LRGILS-NH 2组)和ERK阻断剂组(每组8只)。观察小肠黏膜形态学变化,免疫组化和western blot检测类胰蛋白酶、PAR-2和p-ERK 1/2的表达。通过qRT-PCR检测PAR-2 mRNA。将大鼠随机分为对照组、模型组和云母组(每组8只)。观察黏膜形态学变化。免疫组化法检测类胰蛋白酶、PAR-2和p-ERK 1/2的表达。结果:模型组胰蛋白酶、PAR-2、p-ERK 1/2的表达较对照组增加。与模型组相比,SLIGRL-NH 2组PAR-2和p-ERK 1/2表达增加,而LRGILS-NH 2组无明显变化。与SLIGRL-NH 2组相比,ERK阻断剂组PAR-2表达下调。黏膜肉眼可见病变与PAR-2、p-ERK 1/2表达呈正相关。此外,我们还发现云母可以抑制小肠损伤,这是通过改善肉眼可见的损伤来证明的。云母组类胰蛋白酶、PAR-2、p-ERK 1/2表达较模型组下调。结论:云母通过ERK信号通路抑制NSAIDs所致的小肠损伤。
Objective: The impact of non-steroidal anti-inflammatory drugs (NSAIDs) to damage the small intestine has been well known. Mica, one kind of natural clay, has been widely marketed in China for the treatment of gastric diseases. However, the role and mechanism of mica in small intestinal injure is still unknown. The study was designed to declare the effects of mica on intestinal injury induced by diclofenac in rats. Methods: Rats were randomly divided into control, model, PAR-2 agonist group (SLIGRL-NH2group), control peptide group (LRGILS-NH2 group), and ERK blocker group (eight mice per group). Morphological changes of mucous membrane of small intestine were observed, and the expression of tryptase, PAR-2, and p-ERK1/2 was measured by immunohistochemistry and western blot. PAR-2 mRNA was tested by qRT-PCR. Rats were also randomly divided into control, model, and mica group (eight mice per group). Morphological changes of mucous membrane were observed. The expression of tryptase, PAR-2, and p-ERK1/2 was measured by immunohistochemistry. Results: The expression of trypsin, PAR-2, and p-ERK1/2 was increased in model group compared with control. The expression of PAR-2 and p-ERK1/2 was increased in SLIGRL-NH2 group compared with model, but not LRGILS-NH2 group. The expression of PAR-2 was down-regulated in ERK blocker group compared with SLIGRL-NH2 group. Macroscopically visible lesions of mucous membrane were positively correlated with the expression of PAR-2 and p-ERK1/2. Furthermore, we also found that mica could inhibit small intestinal injure, as evidenced by the improvement of macroscopic damage. Tryptase, PAR-2, and p-ERK1/2 expression was down-regulated in mica group compared with model group. Conclusion: Mica inhibit small intestinal injury induced by NSAIDs via ERK signaling pathway.
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影响因子: 9.3
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