Department of Surgical Intensive Care Unit (SICU), Department of General Surgery, Jinling Hospital, Medical School of Southeast University, No. 305 Zhongshan East Road, Nanjing, 210002 Jiangsu, China.
Pancreatic Center, Department of Gastroenterology, Affiliated Hospital of Yangzhou University, No. 368 Hanjiang Media Road, Yangzhou, 225000 Jiangsu, China.
Mediators Inflamm. 2021 Mar 9;2021:6680456. doi: 10.1155/2021/6680456. eCollection 2021.
Repeated caerulein injection was used to induce AP and chronic pancreatitis (CP) models in mice. The histopathological and serological changes were examined for evaluating the severity of the AP model, and flow cytometry was used for detecting macrophage phagocytosis and phenotype. Meanwhile, clodronate liposomes were used for macrophage depletion in mice. Finally, the CP model was adopted to further observe the protective effect of MaR1.
MaR1 administration manifested the improved histopathological changes and the lower serum levels of amylase and lipase. However, MaR1 played no protective role in the pancreatic acinar cell line . It obviously reduced the macrophage infiltration in the injured pancreas, especially M1-type macrophages. After macrophage clearance, MaR1 showed no further protection . This study also demonstrated that MaR1 could alleviate fibrosis to limit AP progression in the CP model.
Our data suggests that MaR1 was a therapeutic and preventive target for AP in mice, likely operating through its effects on decreased macrophage infiltration and phenotype switch.
采用重复注射蛙皮素的方法诱导小鼠急性胰腺炎(AP)和慢性胰腺炎(CP)模型。通过观察组织病理学和血清学变化来评估 AP 模型的严重程度,并采用流式细胞术检测巨噬细胞的吞噬作用和表型。同时,使用氯膦酸盐脂质体对小鼠进行巨噬细胞耗竭。最后,采用 CP 模型进一步观察 MaR1 的保护作用。
MaR1 给药可改善组织病理学变化,降低血清淀粉酶和脂肪酶水平。然而,MaR1 在胰腺腺泡细胞系中无保护作用。它明显减少了损伤胰腺中的巨噬细胞浸润,尤其是 M1 型巨噬细胞。清除巨噬细胞后,MaR1 没有进一步的保护作用。本研究还表明,MaR1 可减轻纤维化,从而限制 CP 模型中 AP 的进展。
我们的数据表明,MaR1 可能通过减少巨噬细胞浸润和表型转换来减轻纤维化,从而成为治疗和预防小鼠 AP 的靶点。