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茵陈蒿汤减轻大鼠重症急性胰腺炎:网络靶点预测的实验验证

Yin-Chen-Hao Tang Attenuates Severe Acute Pancreatitis in Rat: An Experimental Verification of Network Target Prediction.

作者信息

Xiang Hong, Wang Guijun, Qu Jialin, Xia Shilin, Tao Xufeng, Qi Bing, Zhang Qingkai, Shang Dong

机构信息

College (Institute) of Integrative Medicine, Dalian Medical University Dalian, China.

Department of General Surgery, The First Affiliated Hospital of Jinzhou Medical University Jinzhou, China.

出版信息

Front Pharmacol. 2016 Oct 13;7:378. doi: 10.3389/fphar.2016.00378. eCollection 2016.

DOI:10.3389/fphar.2016.00378
PMID:27790147
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5061810/
Abstract

Yin-Chen-Hao Tang (YCHT) is a classical Chinese medicine compound that has a long history of clinical use in China for the treatment of inflammatory diseases. However, the efficacy and mechanisms of YCHT for the treatment of severe acute pancreatitis (SAP) are not known. The current study investigated the pharmacological properties of YCHT against SAP and its underlying mechanisms. A computational prediction of potential targets of YCHT was initially established based on a network pharmacology simulation. The model suggested that YCHT attenuated SAP progress by apoptosis inducement, anti-inflammation, anti-oxidation and blood lipid regulation. These effects were validated in SAP rats. YCHT administration produced the following results: (1) significantly inhibited the secretion of pancreatic enzymes and protected pancreatic tissue; (2) obviously increased the number of terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive cells and induced apoptosis; (3) markedly inhibited neutrophil infiltration to the impaired pancreas and reduced the inflammatory reaction; (4) notably enhanced the activities of antioxidant enzymes and decreased the nitric oxide synthase levels; (5) significantly reduced the levels of triglycerides, total cholesterol and low-density lipoprotein and increased high-density lipoprotein; and (6) significantly up-regulated peroxisome proliferator-activated receptor-γ (PPARγ) and down-regulated nuclear factor-kappa B (NF-κB). In summary, these results demonstrated that YCHT attenuated SAP progress by inducing apoptosis, repressing inflammation, alleviating oxidative stress and regulating lipid metabolism partially via regulation of the NF-κB/PPARγ signal pathway.

摘要

茵陈蒿汤(YCHT)是一种经典的中药复方,在中国有着悠久的治疗炎症性疾病的临床应用历史。然而,茵陈蒿汤治疗重症急性胰腺炎(SAP)的疗效和机制尚不清楚。本研究调查了茵陈蒿汤对SAP的药理特性及其潜在机制。最初基于网络药理学模拟建立了茵陈蒿汤潜在靶点的计算预测模型。该模型表明,茵陈蒿汤通过诱导细胞凋亡、抗炎、抗氧化和调节血脂来减轻SAP的进展。这些作用在SAP大鼠中得到了验证。给予茵陈蒿汤产生了以下结果:(1)显著抑制胰腺酶的分泌并保护胰腺组织;(2)明显增加末端脱氧核苷酸转移酶dUTP缺口末端标记(TUNEL)阳性细胞的数量并诱导细胞凋亡;(3)显著抑制中性粒细胞向受损胰腺的浸润并减轻炎症反应;(4)显著增强抗氧化酶的活性并降低一氧化氮合酶水平;(5)显著降低甘油三酯、总胆固醇和低密度脂蛋白水平并升高高密度脂蛋白;(6)显著上调过氧化物酶体增殖物激活受体γ(PPARγ)并下调核因子κB(NF-κB)。总之,这些结果表明,茵陈蒿汤通过诱导细胞凋亡、抑制炎症、减轻氧化应激和部分通过调节NF-κB/PPARγ信号通路调节脂质代谢来减轻SAP的进展。

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