上睑下垂
半胱氨酸蛋白酶1
炎症体
急性胰腺炎
腺泡细胞
炎症
药理学
化学
胰腺炎
细胞生物学
细胞凋亡
医学
免疫学
生物
程序性细胞死亡
内科学
生物化学
作者
Hui Chen,Xirong Lu,Beiqi Xu,Gang Cheng,Yuyi Li,Dan Xie
摘要
Abstract Acute pancreatitis represents an inflammatory disease featuring pancreatic necrosis and inflammation. Inflammatory injury of pancreatic acinar cells (PACs) is critically involved in the initiation and progression of acute pancreatitis. Pyroptosis, a new kind of programmed cell death concomitant with a low‐grade inflammatory reaction, plays a function in acute pancreatitis pathology. It is unclear whether saikosaponin d (SSd), a pharmacologically active natural product, could protect PACs by regulating pyroptosis. Here, we established a PAC injury model in vitro using cerulein to treat AR42J cells. SSd restored viability and proliferation and lowered the release of pancreatic enzymes and inflammatory interleukins in cerulein‐treated AR42J cells. Cerulein‐induced pyroptosis was evidenced by typical ultrastructural changes and NLRP3/caspase‐1 activation in AR42J cells, but SSd attenuated cerulein‐induced pyroptosis and inhibited NLRP3/caspase‐1 pathway. Mechanically, SSd reduced mitochondrial damage and mtDNA release, and blocked cGAS‐STING signaling in AR42J cells treated with cerulein, contributing to the inhibition of NLRP3‐mediated pyroptosis. Furthermore, SSd abolished cerulein‐elevated oxidative stress in AR42J cells, leading to the mitigation of mitochondrial damage and inhibition of cGAS‐STING signaling and pyroptosis. In conclusion, SSd protected PACs against cerulein‐induced pyroptosis by alleviating mitochondrial damage and inhibiting the cGAS‐STING pathway, and it could be a therapeutic candidate for acute pancreatitis.
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