Role of p38MAPK intflammatory pathway in the pathogenesis of nonalcoholic steatohepatitis
10.3760/cma.j.issn.1003-9279.2015.01.006
- VernacularTitle:p38MAPK炎症通路在非酒精性脂肪性肝炎发病中的作用研究
- Author:
Ling LI
1
;
Junping SHI
;
Jing LIU
;
Shufei ZANG
;
Xiaojie MA
Author Information
1. 浙江中医药大学护理学院
- Keywords:
Inflamation;
Models,animals
- From:
Chinese Journal of Experimental and Clinical Virology
2015;29(1):16-18
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the expression and significance of p38MAPKin the pathogenesis of nonalcoholic steatohepatitis (NASH).Methods Sixty mice which were 6-weeks-old were randomized by bodyweight into high lipid high fructose group and control group with 30 mice in each and were given the corresponding feed.The nice were sacrificed respectively at the end of weeks 4,8,and 16,and their NASH-related parameters such as liver function,blood lipid etc.were determined,and the liver histopathological changes were evaluated after HE and oil red O staining of liver tissue specimens and NAS scoring was performed; immunohistochemistry and Western Blotting were applied to determine expression of p38MAPK in the model mice at weeks 4,8 and 16,at the same time,RT-PCR was used to determine mRNA expression levels of p38MAPK,TNF-a,MCP-1,IL-1,IL-6 and IL-8.Results As compared with the control mice at the same stage,the oil red O stained area and density increased in the high lipid high fructose group; HE staining showed that foci of different degree occurred with time after the model was established.The NAS score at the end of model establishment was 5-8 points,which reached the diagnostic criterion for NASH.At the end of 4th and 8th weeks,total cholesterol,high density lipoprotein,low density lipoprotein significantly increased as compared to the control group.At the end of the 16th week,the liver function tests and blood lipid of the high lipid high fructose group significantly increased.MCP-1 and IL-1 markedly increased at the early stage,TNF-α and IL-8 increased at the end of the 8th week,while p38MAPK and IL-6 showed a trend of increase,and increased significantly at the end of 16th week.Immunohistochemistry for p-p38MAPK showed nuclear stainingat 8th and 16th weeks; Western Blotting showed significant increase of p38MAPK expression in the model group at 4,8,and 16th weeks in the liver tissue as compared with the control group.Conclusion Mouse model of NASH was successfully established by using modified western food-like feed,and in the model group p38MAPK and inflammatory factors play roles in formation of NASH,and p38MAPK and IL-6 may be used as a basis for assessment of targeted therapy of NASH.
