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Updated: Dec 8, 2025
Colon Ascendens Stent Peritonitis CASP - a Standardized Model for Polymicrobial Abdominal Sepsis
Published on: December 18, 2010
Berberine reduces gut-vascular barrier permeability via modulation of ApoM/S1P pathway in a model of polymicrobial
Yanning Li1, Jun Zhou1, Jiasheng Qiu1
1Department of Gastrointestinal Surgery, Maoming People's Hospital, Maoming Clinical Medical College, Guangdong Medical University, Guangdong Province, China.
Aims:
The hyperpermeability of gut-vascular barrier (GVB) plays a role in gut-derived sepsis. The goal of this study was to evaluate if berberine might improve hepatic apolipoprotein M (ApoM) generation and raise plasma ApoM level to protect the compromised GVB.
Materials And Methods:
The compromised GVB was induced by sepsis. Hepatic ApoM mRNA and phosphoenolpyruvate carboxykinase (PEPCK) mRNA and plasma ApoM level were assayed by qRT-PCR and ELISA, respectively. The permeability of intestinal capillary in vivo and of rat intestinal microvascular endothelial cells (RIMECs) in vitro was assayed by FITC-dextran. The blood glucose was detected by a glucometer. Plasma insulin, TNF-α and IL-1β were assayed by ELISA. The plasmalemma vesicle-associated protein-1 (PV1), β-catenin and occludin in RIMECs were assayed by Western blot.
Key Findings:
Sepsis decreased hepatic ApoM mRNA and plasma ApoM level, but raised hepatic PEPCK mRNA and plasma glucose, insulin, TNF-α, and IL-1β levels. The increased vascular endothelial permeability was abrogated by recombinant rat ApoM in vivo or ApoM-bound S1P in vitro. ApoM-bound S1P decreased PV1 but increased occludin and β-catenin expression in LPS-treated RIMECs. Berberine in a dose-dependent manner raised hepatic ApoM mRNA and plasma ApoM level, but decreased septic hyperglycemia, insulin resistance and plasma TNF-α and IL-1β levels. Berberine reduced sepsis-induced PEPCK and TLR4 mRNA overexpression in the liver.
Significance:
This study demonstrated berberine inhibited TLR4-mediated hyperglycemia, insulin resistance and proinflammatory molecule production, thereby increasing ApoM gene expression and plasma ApoM. Berberine protected the damaged GVB via modulation of ApoM/S1P pathway.
