Neovascularization aggravated hepatic fibrosis in combined hypoxia NASH rat model
10.3760/cma.j.issn.1007-3418.2017.07.008
- VernacularTitle: 新生血管生成促进合并缺氧的非酒精性脂肪性肝炎大鼠肝纤维化形成的研究
- Author:
Jiang LIU
1
;
Wei WU
1
;
Donghua GU
1
;
Chunyan LIU
1
;
Quan DONG
1
;
Yunliang YAO
2
;
Chunsheng WANG
2
;
Xiaoping CHEN
3
;
Hongxia YANG
3
Author Information
1. Department of Gastroenterology, Huzhou central Hospital, Zhejiang 313000, China
2. Huzhou University, Zhejiang 313000, China
3. Huzhou Food and Drug Control Institute, Zhejiang 313000, China
- Publication Type:Journal Article
- Keywords:
Anoxia;
Fibrosis;
Neovascularization
- From:
Chinese Journal of Hepatology
2017;25(7):517-522
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To optimize the construction of combined hypoxia NASH rat model on the basis of preliminary work, and to explore the role of neovascularization in the process of hepatic fibrosis.
Methods:32 rats were divided randomly to four groups that were null control group(A group ), hypoxia group(B group), high fat diet group(C group ) and high fat diet plus hypoxia group (D group ),treated with null , Intraperitoneal injection of NaNO2, high fat diet and high fat diet plus Intraperitoneal injection of NaNO2 respectively. Every group was observed for 16 weeks, B and D group was treated with Intraperitoneal injection of NaNO2 20 mg/kg.d at the laster 8 weeks. Liver histology NASH activity score(NAS) and Fibro score(FibroS), biochemical index were detected in this combined hypoxia NASH rat model(D group), meanwhile the changes of HIF1α, inflammatory factor and neovascularization were measured by ELISA, realtime PCR and immunohistochemistry.
Results:Liver tissue NAS > 4 was seen in C and D group. D group showed NASH characteristics, including significantly steatosis at liver acinar 3 area(mostly a microvesicular type fat droplets mixed with macrovesicular type), hepatocyte balloon degeneration, obvious lobular inflammation, while fibrosis score increased significantly, including visible hepatic sinusoid fibrosis, fibrosis around portal vein, and bridging fibrosis in a considerable portion of the rats. Compared with C group, biochemical indicators of aspartate aminotransferase (AST), HIF1α, neovascularization-related VEGFA, VEGFR2 mRNA level increased obviously and the expression of immunohistochemistry VEGFR2, CD34 enhanced markedly in D group(p < 0.05).
Conclusion:A combined hypoxia NASH rat model can be established throught feeding 16 weeks’ high-fat diet then intraperitoneal injection of NaNO2 20 mg / kg.d at the laster 8 weeks, meanwhile chronic hypoxia can accelerate this combined hypoxia NASH model liver fibrosis process. In this process neovascularization promoted the formation of hepatic fibrosis in this model.
