背景:左金丸(ZJP)自古以来就是中国治疗胃肠道疾病的经典方剂。但其对非甾体类抗炎药(NSAIDs)所致胃损伤(GI)的作用尚不清楚。
目的:本研究旨在探讨ZJP对吲哚美辛(IDO)所致胃损伤的治疗作用及其分子机制。
方法:通过口服5mg/kgIDO在大鼠中诱导GI。然后用ZJP(1.26,2.52,5.04g/kg,ig)。食物摄入的变化,体重,进行了胃pH和一般状态观察以确定ZJP在IDO诱导的GI中的改善:HE染色和AB-PAS染色以表征胃粘膜的厚度和微粘膜损伤;为了阐明ZJP对IDO诱导的炎症损伤的影响,MPO免疫组化法观察胃组织炎性浸润,和TNF-α的含量,测量IL-6和IL-10。此外,在网络药理学的帮助下,预测了ZJP治疗IDO诱导的GI的调节机制,以及关键蛋白ERK的表达水平,p-ERK,P38,p-P38,JNK,测定p-JNK以阐明ZJP的分子机制。
结果:目前的数据有力地表明,ZJP减轻了食物摄入量的减少,IDO引起的体重减轻和胃损伤,使胃pH和粘膜厚度恢复正常。此外,ZJP可以降低MPO水平以减轻胃组织的炎性浸润。同时,ZJP可以下调TNF-α和IL-6的表达,上调IL-10的表达,从而减轻炎症损伤,创造一个疗愈的环境。此外,ZJP能显著抑制ERK的磷酸化,p38和JNK,导致炎症因子的增加和胃黏膜的损伤。
结论:ZJP通过抑制MAPK信号通路改善局部炎症,对IDO诱导的胃肠道有良好的治疗作用。本研究对ZJP防治NSAID所致胃损伤的研究具有借鉴意义。此外,ZJP可能是预防和治疗NSAID引起的胃病的新治疗选择。
BACKGROUND: Zuojin Pill (ZJP) has been a classic prescription for the treatment of gastrointestinal diseases in China since ancient times. But its effect on non-steroidal anti-inflammatory drugs (NSAIDs) induced gastric injury (GI) is still uncharted.
OBJECTIVE: This study aims to investigate the therapeutic effect and molecular mechanism of ZJP on indomethacin (IDO) induced gastric injury.
METHODS: GI was induced in rat by oral administration of 5 mg/kg IDO. Then the rats were treated with ZJP (1.26, 2.52, 5.04 g/kg, ig). The changes of food intake, body weight, gastric pH and general state observation were carried out to determine the improvement of ZJP in IDO-induced GI: HE staining and AB-PAS staining was analyzed to characterize the thickness of gastric mucosa and micro mucosal injury; in order to elucidate the effect of ZJP on IDO-induced inflammatory injury, the inflammatory infiltration of gastric tissue was observed by MPO immunohistochemical method, and the contents of TNF-α, IL-6 and IL-10 were measured. Furthermore, the regulatory mechanism of ZJP in treating IDO-induced GI was predicted with the help of network pharmacology, and the expression levels of key proteins ERK, p-ERK, P38, p-P38, JNK, p-JNK were determined to elucidate the molecular mechanism of ZJP.
RESULTS: Current data strongly demonstrated that ZJP alleviated food intake reduction, weight loss and gastric injury caused by IDO and made gastric pH and mucosal thickness return to normal. In addition, ZJP could reduce the level of MPO to alleviate the inflammatory infiltration of gastric tissue. Simultaneously, ZJP could down regulate the expression of TNF-α and IL-6 and up regulate the expression of IL-10 to reduce the damage caused by inflammatory, and create a healing environment. Furthermore, ZJP could significantly inhibit the phosphorylation of ERK, p38 and JNK, which leaded to the increase of inflammatory factors and the damage of gastric mucosa.
CONCLUSIONS: ZJP improved local inflammation by inhibiting MAPK signaling pathway, and had a good therapeutic effect on IDO-induced GI. This study has reference significance for the study of ZJP in the prevention and treatment of NSAID induced gastric injury. In addition, ZJP may be a new treatment option for the prevention and treatment of NSAID induced gastric disease.