清胰化积汤通过调控 circHipk3/miR-193a-5p/NLRP3 通路抑制胰腺腺泡细胞焦亡。
Qingjie Huagong decoction inhibits pancreatic acinar cell pyroptosis by regulating circHipk3/miR-193a-5p/NLRP3 pathway.
机构信息
The First Clinical School of Medicine, Guangxi University of Traditional Chinese Medicine, Nanning 530000, China.
Department of Gastroenterology, Chongqing Traditional Chinese Medicine Hospital, Chongqing 400021, China.
出版信息
Phytomedicine. 2024 Apr;126:155265. doi: 10.1016/j.phymed.2023.155265. Epub 2023 Dec 7.
BACKGROUND
Safer and more effective drugs are needed for the treatment of acute pancreatitis (AP). Qingjie Huagong decoction (QJHGD) has been applied to treat AP for many years and has shown good clinical effects. However, the potential mechanism has not yet been determined.
PURPOSE
To investigate the role and underlying mechanism of the effects of QJHGD on AP both in vitro and in vivo.
METHODS
QJHGD was characterized by UHPLC-Q-Orbitrap-MS. The protective effect of QJHDG and the underlying mechanism were investigated in MPC-83 cells in vitro. A caerulein-induced AP model was established to evaluate the protective effect of QJHGD in mice. CCK-8 assays were used to detect cell viability. The contents of inflammatory mediators were determined by ELISA. Expression levels of circRNA, miRNA and mRNA were determined by qRT-PCR. Protein expression was determined using Western blot. Pancreatic tissues were assessed by hematoxylin and eosin staining as well as immunohistochemical and immunofluorescence analyses. Pull-down and luciferase activity assays were performed to determine the regulatory relationships of circHipk3, miR-193a-5p and NLRP3.
RESULTS
Our results confirmed that mmu-miR-193a-5p was sponged by mmu-circHipk3, and NLRP3 was a target of miR-193a-5p. In vitro experiments showed that QJHGD enhanced MPC-83 cell viability by regulating circHipk3 sponging mir-193a-5 targeting NLRP3 and inhibiting pyroptosis-related factors. Finally, we showed that QJHGD ameliorated pancreatic tissue injury in AP mice via this pathway.
CONCLUSION
This study demonstrate that QJHDG exerted its anti-AP effects via the circHipk3/miR-193a-5p/NLRP3 pathway, revealing a novel mechanism for the therapeutic effect of QJHDG on AP.
背景
急性胰腺炎（AP）的治疗需要更安全、更有效的药物。清胰化积汤（QJHGD）已应用于治疗 AP 多年，显示出良好的临床疗效。然而，其潜在机制尚未确定。
目的
探讨 QJHGD 在体外和体内治疗 AP 的作用及其潜在机制。
方法
采用 UHPLC-Q-Orbitrap-MS 对 QJHGD 进行表征。在 MPC-83 细胞体外研究 QJHDG 的保护作用及其潜在机制。建立胰酶诱导的 AP 模型，评估 QJHGD 在小鼠中的保护作用。CCK-8 法检测细胞活力。ELISA 法测定炎症介质含量。qRT-PCR 检测 circRNA、miRNA 和 mRNA 的表达水平。Western blot 检测蛋白表达。采用苏木精和伊红染色以及免疫组化和免疫荧光分析评估胰腺组织。采用 pull-down 和荧光素酶活性测定法确定 circHipk3、miR-193a-5p 和 NLRP3 的调控关系。
结果
本研究证实 mmu-miR-193a-5p 是 mmu-circHipk3 的海绵体，NLRP3 是 miR-193a-5p 的靶标。体外实验表明，QJHGD 通过调节 circHipk3 海绵 miR-193a-5 靶向 NLRP3 并抑制细胞焦亡相关因子，增强 MPC-83 细胞活力。最后，我们表明 QJHGD 通过该途径改善 AP 小鼠的胰腺组织损伤。
结论
本研究表明，QJHDG 通过 circHipk3/miR-193a-5p/NLRP3 途径发挥其抗 AP 作用，揭示了 QJHDG 治疗 AP 的治疗作用的新机制。
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