Department of Clinical Pharmacy, West China Hospital of Sichuan University, Chengdu 610041, China.
J Tradit Chin Med. 2019 Apr;39(2):166-173.
To investigate the effect of Chaiqin Chengqi decoction (CQCQD) on acute pancreatitis (AP) by janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway in vitro and in vivo.
AP was induced by caerulein both in AR42J cells and in mice. AR42J cells were divided into five groups: the control group, the AP group, the CQCQD group, JAK/STAT signaling pathway inhibitor AG490 group, and the CQCQD and AG490 group. After induction, cellular supernatant of five groups were collected for measuring the concentrations of inflammatory cytokine amylase, interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), nuclear factor κB (NF-κB) by enzyme-linked immunosorbent assay and the expression of JAK-2, STAT-3 signaling transduction proteins by Western blot, respectively. Experiments in mice were performed similar to that of in AR42J cells.
Treatment of AR42J cells with CQCQD reduced the pancreatic injury and negatively regulated the activities of amylase, as well as inhibited expression of several inflammatory cytokines such as IL-6, TNF-α, IL-1β, NF-κB. Administration of CQCQD significantly inhibited JAK-2 activation and down-regulated phosphorylation of downstream substrate STAT-3 the same as AG490, resulting in inhibition of inflammatory mediators and amelioration of pancreatitis.
The results suggested that CQCQD exerted anti-inflammatory effects on AP via reducing expression and phosphorylation of JAK and STAT.
通过 Janus 激酶/信号转导与转录激活因子(JAK/STAT)信号通路研究柴芩承气汤(CQCQD)对体外和体内急性胰腺炎(AP)的影响。
用胆酸钠诱导 AR42J 细胞和小鼠的 AP。将 AR42J 细胞分为五组:对照组、AP 组、CQCQD 组、JAK/STAT 信号通路抑制剂 AG490 组和 CQCQD+AG490 组。诱导后,收集五组细胞上清液,采用酶联免疫吸附试验测定炎症细胞因子淀粉酶、白细胞介素 6(IL-6)、肿瘤坏死因子 α(TNF-α)、白细胞介素 1β(IL-1β)、核因子 κB(NF-κB)的浓度,Western blot 法检测 JAK-2、STAT-3 信号转导蛋白的表达。在小鼠中的实验与 AR42J 细胞中的实验类似。
CQCQD 处理 AR42J 细胞可减轻胰腺损伤,负调控淀粉酶活性,并抑制白细胞介素 6、肿瘤坏死因子 α、白细胞介素 1β、NF-κB 等多种炎症细胞因子的表达。CQCQD 给药与 AG490 一样,明显抑制 JAK-2 激活并下调下游底物 STAT-3 的磷酸化,从而抑制炎症介质并改善胰腺炎。
结果表明,CQCQD 通过降低 JAK 和 STAT 的表达和磷酸化对 AP 发挥抗炎作用。