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大柴胡汤通过抑制慢性胰腺炎中巨噬细胞浸润来改善胰腺纤维化。

Dachaihu decoction ameliorates pancreatic fibrosis by inhibiting macrophage infiltration in chronic pancreatitis.

机构信息

Department of Pathophysiology, Shaanxi University of Chinese Medicine, Xianyang 712046, Shaanxi Province, China.

Medical Experiment Center, Shaanxi University of Chinese Medicine, Xianyang 712046, Shaanxi Province, China.

出版信息

World J Gastroenterol. 2017 Oct 28;23(40):7242-7252. doi: 10.3748/wjg.v23.i40.7242.

Abstract

AIM

To explore the role of macrophages in chronic pancreatitis (CP) and the effect of Dachaihu decoction (DCHD) on pancreatic fibrosis in mice.

METHODS

KunMing mice were randomly divided into a control group, CP group, and DCHD group. In the CP and DCHD groups, mice were intraperitoneally injected with 20% L-arginine (3 g/kg twice 1 d/wk for 6 wk). Mice in the DCHD group were administered DCHD intragastrically at a dose of 14 g/kg/d 1 wk after CP induction. At 2 wk, 4 wk and 6 wk post-modeling, the morphology of the pancreas was observed using hematoxylin and eosin, and Masson staining. Interleukin-6 (IL-6) serum levels were assayed using an enzyme-linked immunosorbent assay. Double immunofluorescence staining was performed to observe the co-expression of F4/80 and IL-6 in the pancreas. Inflammatory factors including monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α) and IL-6 were determined using real time-polymerase chain reaction. Western blot analysis was used to detect fibronectin levels in the pancreas.

RESULTS

Compared with the control group, mice with 20% L-arginine-induced CP had obvious macrophage infiltration and a higher level of fibrosis. IL-6 serum concentrations were significantly increased. Double immunofluorescence staining showed that IL-6 and F4/80 were co-expressed in the pancreas. With the administration of DCHD, the infiltration of macrophages and degree of fibrosis in the pancreas were significantly attenuated; IL-6, MCP-1 and MIP-1α mRNA, and fibronectin levels were reduced.

CONCLUSION

The dominant role of macrophages in the development of CP was mainly related to IL-6 production. DCHD was effective in ameliorating pancreatic fibrosis by inhibiting macrophage infiltration and inflammatory factor secretion in the pancreas.

摘要

目的

探讨巨噬细胞在慢性胰腺炎(CP)中的作用及大柴胡汤(DCHD)对小鼠胰腺纤维化的影响。

方法

昆明小鼠随机分为对照组、CP 组和 DCHD 组。CP 组和 DCHD 组小鼠腹腔注射 20%L-精氨酸(3 g/kg,每周 2 次,共 6 周)。CP 诱导后 1 周,DCHD 组小鼠给予 DCHD 灌胃,剂量为 14 g/kg/d。建模后 2、4、6 周,采用苏木精-伊红和 Masson 染色观察胰腺形态。采用酶联免疫吸附试验测定血清白细胞介素-6(IL-6)水平。采用双免疫荧光染色观察胰腺中 F4/80 和 IL-6 的共表达。采用实时聚合酶链反应检测单核细胞趋化蛋白-1(MCP-1)、巨噬细胞炎性蛋白-1α(MIP-1α)和 IL-6 等炎症因子。采用 Western blot 分析检测胰腺中纤维连接蛋白水平。

结果

与对照组相比,20%L-精氨酸诱导的 CP 小鼠巨噬细胞浸润明显,纤维化程度更高。IL-6 血清浓度显著升高。双免疫荧光染色显示,IL-6 和 F4/80 在胰腺中共同表达。给予 DCHD 治疗后,胰腺巨噬细胞浸润和纤维化程度明显减轻;IL-6、MCP-1 和 MIP-1αmRNA 及纤维连接蛋白水平降低。

结论

巨噬细胞在 CP 发展中的主导作用主要与 IL-6 的产生有关。DCHD 通过抑制胰腺中巨噬细胞浸润和炎症因子的分泌,有效改善胰腺纤维化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c172/5677205/80e0027d3833/WJG-23-7242-g001.jpg

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