Shanghai Institute of Geriatrics, Huadong Hospital, Fudan University, Shanghai, 200040, PR China.
Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200030, PR China.
Biochem Biophys Res Commun. 2019 Feb 5;509(2):421-428. doi: 10.1016/j.bbrc.2018.12.108. Epub 2018 Dec 26.
Acute pancreatitis (AP) is a severe and frequently lethal disorder, but the precise mechanisms are not well understood and there is lack of effective drugs. Therefore, our study examined the in vivo intervention effects of genistein and elucidated its mechanism in acute experimental pancreatitis models. We used cerulein or taurocholate to induce acute pancreatitis (AP) in Sprague-Dawley rats with prior genistein treatment. Histological examination of the pancreas was performed and the expression of unfolded protein response (UPR) components and apoptotic mediators like caspase 12 and c-Jun N-terminal protein kinase (JNK) were measured. The amount of apoptosis in pancreatic acinar cells was also determined. Our studies found that the severity of cerulein- or taurocholate-induced AP was rescued by prior genistein treatment. Genistein stimulated the activation of multiple endoplasmic reticulum (ER) stress-related regulators like GRP78, PERK, eIF2α, and upregulated the expression of the apoptotic genes, caspase 12 and CHOP. Moreover, TUNEL assays showed that genistein treatment promoted acinar cell apoptosis. Taken together, we speculated that ER stress-associated apoptotic pathways in AP are induced by genistein, which showed cytoprotective capacity in the exocrine pancreas. These data suggest novel therapeutic strategies that employ genistein in the prevention of AP.
急性胰腺炎（AP）是一种严重且常致命的疾病，但确切的发病机制尚未完全阐明，且缺乏有效的治疗药物。因此，我们的研究检测了染料木黄酮在体内对急性实验性胰腺炎模型的干预作用，并阐明了其作用机制。我们使用鹅去氧胆酸或牛磺胆酸钠诱导 Sprague-Dawley 大鼠急性胰腺炎（AP），并用染料木黄酮预先处理。对胰腺进行组织学检查，并测量未折叠蛋白反应（UPR）成分和凋亡介质（如 caspase 12 和 c-Jun N-末端蛋白激酶（JNK））的表达。还测定了胰腺腺泡细胞的凋亡量。我们的研究发现，染料木黄酮预处理可挽救鹅去氧胆酸或牛磺胆酸钠诱导的 AP 的严重程度。染料木黄酮刺激多种内质网（ER）应激相关调节剂的激活，如 GRP78、PERK、eIF2α，并上调凋亡基因 caspase 12 和 CHOP 的表达。此外，TUNEL 测定表明染料木黄酮处理促进了腺泡细胞凋亡。总之，我们推测 ER 应激相关的凋亡途径在 AP 中被染料木黄酮诱导，其在胰腺外分泌中显示出细胞保护能力。这些数据提示了一种新的治疗策略，即在预防 AP 中使用染料木黄酮。
