Shi Chenyuan, Hou Chaoqun, Zhu Xiaole, Huang Dongya, Peng Yunpeng, Tu Min, Li Qiang, Miao Yi
Pancreas Centre, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China; Pancreas Institute, Nanjing Medical University, Nanjing, Jiangsu Province, China.
Pancreas Centre, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China; Pancreas Institute, Nanjing Medical University, Nanjing, Jiangsu Province, China.
Biomed Pharmacother. 2018 Dec;108:50-57. doi: 10.1016/j.biopha.2018.09.035. Epub 2018 Sep 11.
Severe acute pancreatitis (SAP) is a medical emergency that is often associated with multiple organ failure and high mortality. Although an SAP diagnosis requires prompt treatment, therapeutic options remain limited. SRT1720 is a newly formulatedSIRT1 activator that exerts multiple pharmacological activities with beneficial health effects. However, its potential as an SAP treatment has not been explored. The current study assessed the effect of SRT1720 on a rat model of sodium taurocholate-induced SAP and explored the underlying mechanism. SAP was induced in rats by retrograde injection of a 3.5% sodium taurocholate solution (1 ml/kg) in the biliopancreatic duct. SRT1720 (5 mg/kg) was administered intraperitoneally after sodium taurocholate exposure. Serum samples were analysed for inflammatory cytokine levels and select enzymatic activities using the enzyme-linked immunosorbent assay and commercial enzyme activity assay kits, respectively; protein expression levels were evaluated by western blotting; mRNA levels of biomarkers were determined by quantitative real-time PCR; histopathological changes were analysed by haematoxylin and eosin staining and immunohistochemistry.SRT1720 treatment significantly reduced serum amylase, lipase, pancreatic histological scores, proinflammatory cytokine (TNF-α and IL-6) levels, and expression of NF-κB and p65 in sodium taurocholate-induced SAP rats. Importantly, the treatment stimulated SIRT1 and IκBα levels in pancreatic tissue. Our data suggest that SRT1720 protects rats from sodium taurocholate-induced SAP by suppressing the NF-κB signalling pathway.
重症急性胰腺炎（SAP）是一种医疗急症，常伴有多器官功能衰竭和高死亡率。尽管SAP诊断需要及时治疗，但治疗选择仍然有限。SRT1720是一种新配制的SIRT1激活剂，具有多种药理活性，对健康有益。然而，其作为SAP治疗药物的潜力尚未得到探索。本研究评估了SRT1720对牛磺胆酸钠诱导的SAP大鼠模型的影响，并探讨了其潜在机制。通过在大鼠胆胰管逆行注射3.5%牛磺胆酸钠溶液（1 ml/kg）诱导SAP。在暴露于牛磺胆酸钠后腹腔注射SRT1720（5 mg/kg）。分别使用酶联免疫吸附测定法和商业酶活性测定试剂盒分析血清样本中的炎性细胞因子水平和选定的酶活性；通过蛋白质印迹法评估蛋白质表达水平；通过定量实时PCR测定生物标志物的mRNA水平；通过苏木精和伊红染色以及免疫组织化学分析组织病理学变化。SRT1720治疗显著降低了牛磺胆酸钠诱导的SAP大鼠的血清淀粉酶、脂肪酶、胰腺组织学评分、促炎细胞因子（TNF-α和IL-6）水平以及NF-κB和p65的表达。重要的是，该治疗刺激了胰腺组织中SIRT1和IκBα的水平。我们的数据表明，SRT1720通过抑制NF-κB信号通路保护大鼠免受牛磺胆酸钠诱导的SAP的影响。
