Effects of cannabinoid HU210 on experimental acute pancreatitis and possible relationship with Toll-like receptor 4 signaling pathway
10.3969/j.issn.1000-4718.2017.06.025
- VernacularTitle:大麻制剂HU210对实验性急性胰腺炎的干预作用及其与Toll样受体4信号通路的可能关系
- Author:
Ruiqin ZHANG
;
Sisi LIN
;
Min LI
;
Li SHEN
;
Kun LI
;
Yongyu LI
- Keywords:
Acute pancreatitis;
Cannabinoids;
Toll-like receptor 4;
Inflammatory mediators
- From:
Chinese Journal of Pathophysiology
2017;33(6):1112-1118
- CountryChina
- Language:Chinese
-
Abstract:
AIM:Using Toll-like receptor 4 gene knockout (tlr4-/-) mice and the wild-type (WT) mice with the same C57BL/10J genetic background, the effects of HU210, a cannabis preparation, on caerulein (CAE)-induced acute pancreatitis (AP) and the potential mechanisms were investigated.METHODS:WT or tlr4-/-mice were randomly divided into AP group, AP+HU210 group and control group.AP was induced by intraperitoneal injection of CAE (50 μg·kg-1·h-1) for a total of 6 times and lipopolysaccharide (LPS) at 10 mg/kg 6 h after the first injection of CAE.HU210 (50 μg/kg) was given 30 min before and 4 h after the first injection of CAE in AP+HU210 group.The animals in control group were given normal saline instead of CAE and LPS in the same way.The mice were sacrificed 3 h after the last injection.The blood, the pancreas, the lungs and the intestinal Peyer's patches were harvested.RESULTS:Compared with control group, the pancreatic pathological score and P38 protein expression, plasma amylase activity and inflammatory mediator levels, and lung MPO activity were significant increased (P<0.05) in both WT and tlr4-/-mice with AP.Compared with the WT mice with AP, the tlr4-/-mice with AP showed significantly low levels of IL-6, TNF-α and MCP-1 in the plasma, low expression levels of pancreatic P38 and p-P38 protein (P<0.05), and mild alterations of CD3+ T-lymphocytes, CD4+ T-lymphocytes and the ratio of CD4+/CD8+ (P<0.05).The administration of HU210 attenuated the pancreatic pathological changes and the lung MPO activity in both stains of mice with AP (P<0.05).However, the inhi-bitory effects of HU210 on the increased amylase activity in the plasma and the increased protein levels of pancreatic P38 and p-P38 were remarkable (P<0.05) in WT mice instead of in tlr4-/-mice.CONCLUSION:TLR4 is mainly involved in AP-related systemic inflammatory response and its mechanism may be dependent on TLR4-P38 MAPK signaling pathway.The intervention of HU210 in AP plays a protective role mainly by inhibiting the infiltration of inflammatory cells, and the relationship with TLR4 signaling pathway is not obvious.
