清胰汤调节重症急性胰腺炎纤维化通路的组织学和分子研究

Shayan Chen , Zhihuang Wu , Wendie Yu , Di Zou , Jiongtang Lu
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引用次数: 0

摘要

清胰汤(QYD)是一种由大柴胡汤衍生而来的中药制剂,用于治疗严重急性胰腺炎(SAP)。虽然QYD的成分,大黄和柴胡,具有已知的抗纤维化特性,但它们在SAP中的机制尚不清楚。本研究在脂多糖(LPS)和蓝蛋白诱导的小鼠sap模型中探讨了清芪多糖的抗纤维化作用及其机制。方法通过腹腔注射蓝蛋白和LPS诱导小鼠sap。芪黄酮+SAP组口服芪黄酮,剂量为临床剂量的2倍。在建模和QYD治疗后,采集胰腺组织,用组织学方法检查纤维化参数。此外,采用Western blotting和激光扫描共聚焦显微镜观察芪黄酮对胰腺组织的抗纤维化作用。结果SAP小鼠胰腺组织组织学检查显示明显的组织损伤。然而,QYD治疗改善了SAP的组织学严重程度。此外,QYD降低了胰腺纤维化和PSC激活标志物(包括α-SMA、胶原和纤维连接蛋白)的表达,同时提高了胰腺腺泡细胞的存活率,恢复了外分泌胰腺功能。在机制上,QYD治疗抑制JNK、ERK和p38 MAPK通路的激活,并阻止胰腺组织中i - κ b α的降解。结论本研究证实SAP患者存在轻度胰腺纤维化,并揭示清芪多糖通过抑制JNK、ERK、p38 MAPK信号通路及抑制i- κ b α降解而具有抗纤维化作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Qingyi decoction modulates fibrotic pathways in severe acute pancreatitis: A histological and molecular study

Qingyi decoction modulates fibrotic pathways in severe acute pancreatitis: A histological and molecular study

Background

Qingyi Decoction (QYD), a traditional Chinese medicine (TCM) formulation derived from Dachaihu Decoction, is used to treat severe acute pancreatitis (SAP). While QYD's components, rhubarb and bupleurum, possess known anti-fibrotic properties, their mechanisms in SAP remain unclear. This study investigated QYD's anti-fibrotic effects and underlying mechanisms in a lipopolysaccharide (LPS)- and cerulein-induced mouse model of SAP.

Methods

SAP was induced in mice by intraperitoneal injection of cerulein and LPS. The QYD+SAP group received oral administration of QYD at twice the clinical dosage. Following modeling and QYD treatment, pancreatic tissues were harvested for examination of fibrotic parameters using histological methods. Additionally, the anti-fibrogenic effects of QYD on pancreatic tissue were investigated using Western blotting and laser scanning confocal microscopy.

Results

In SAP mice, histological examination of pancreatic tissues revealed significant tissue damage. However, QYD treatment ameliorated the histological severity of SAP. Furthermore, QYD decreased the expression of pancreatic fibrosis and PSC activation markers, including α-SMA, collagen, and fibronectin, while enhancing pancreatic acinar cell survival and restoring exocrine pancreatic function. Mechanistically, QYD treatment inhibited the activation of JNK, ERK, and p38 MAPK pathways, as well as prevented IκBα degradation in pancreatic tissues.

Conclusion

This study demonstrates the presence of mild pancreatic fibrosis in SAP and reveals QYD's anti-fibrotic effects through the inhibition of JNK, ERK, and p38 MAPK signaling pathways and the prevention of IκBα degradation.
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