Department of Gastroenterology, the Shidong Hospital of Shanghai, Anhui Medical University, Shanghai, China.
Department of Emergency, the Tenth People's Hospital of Shanghai, Tongji University, Shanghai, China.
Int Immunopharmacol. 2018 Mar;56:18-28. doi: 10.1016/j.intimp.2018.01.011. Epub 2018 Jan 9.
A various of pharmacological effects of astaxanthin has been confirmed. However, the mechanism underlying protective effect of astaxanthin on acute pancreatitis (AP) induced by cerulein still unclear. The present study is to investigate the mechanism underlying the effect of astaxanthin on autophagy and apoptosis via the JAK/STAT3 pathway.
Intraperitoneal injection of cerulein at hourly intervals followed by lipopolysaccharide injection were used in Balb/C mice. Vehicle or astaxanthin, which intraperitoneal injected in two doses (20 mg/kg and 40 mg/kg), were injected in mice 1 h before the first cerulein injection. At 3 h after the last injection, when the pathological changes were most severe, pancreatic tissue was analyzed by pathologically scored and hematoxylin and eosin (H&E) staining. The severity of AP was assessed by histological grading, proinflammatory cytokine levels, biochemistry, myeloperoxidase (MPO) activity, and analysis of JAK/STAT3 activity.
Astaxanthin administration markedly reduced serum digestive enzyme activities, pancreatic histological scores, proinflammatory cytokine levels (tumor necrosis factor-α (TNF-α), Interleukin-1β (IL-1β), and Interleukin-6 (IL-6)), MPO and JAK/STAT3 activity.
Collectively, these results indicate that astaxanthin inhibits pancreatic injury in AP by targeting JAK/STAT3-mediated apoptosis and autophagy.
虾青素具有多种药理作用。然而,虾青素对雨蛙肽诱导的急性胰腺炎(AP)的保护作用的机制尚不清楚。本研究旨在通过 JAK/STAT3 通路探讨虾青素对自噬和细胞凋亡的作用机制。
采用雨蛙肽间隔 1 小时腹腔注射,再给予脂多糖注射的方法建立 Balb/C 小鼠 AP 模型。在第一次雨蛙肽注射前 1 小时,腹腔注射 vehicle 或虾青素(20mg/kg 和 40mg/kg 两种剂量)。末次注射后 3 小时,当病理变化最严重时,通过病理评分和苏木精-伊红(H&E)染色分析胰腺组织。通过组织学分级、促炎细胞因子水平、生化、髓过氧化物酶(MPO)活性和 JAK/STAT3 活性分析来评估 AP 的严重程度。
虾青素给药可显著降低血清消化酶活性、胰腺组织学评分、促炎细胞因子水平(肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)和白细胞介素-6(IL-6))、MPO 和 JAK/STAT3 活性。
综上所述,这些结果表明虾青素通过靶向 JAK/STAT3 介导的细胞凋亡和自噬抑制 AP 中的胰腺损伤。