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Application of FXR expression interference reagent in preparation of anti-hepatic fibrosis drugs
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An anti-liver fibrosis, reagent technology, applied in the field of biomedicine to achieve the effect of maintaining integrity
Inactive Publication Date: 2018-05-29
CHINA PHARM UNIV
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However, the current research is still limited to the role of FXR transcriptional activity in diseases, ignoring the role of FXR expression in the physiological and pathological process of the liver; therefore, it is also limited to the development of reagents that regulate FXR transcriptional activity, while ignoring the intervention of FXR expression Reagents, including drugs and genes (viral and non-viral vectors) and other reagents
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Embodiment 1
[0023] Example 1 The levels of FXR and its downstream signaling molecules are significantly down-regulated in the state of liver fibrosis
[0024] 1 Experimental materials
[0025] Experimental mice (C57BL / 6) were purchased from the Comparative Medicine Center of Yangzhou University;
[0026] CCl 4 Purchased from Shanghai Lingfeng Chemical Reagent Company, mineral oil was purchased from Sigma-Aldrich Company, TrizolRNAiso plus was purchased from Takara Company, reverse transcription kit and SYBR Green were purchased from Applied Biosystems Company, and the primers used were synthesized by Life Company.
[0027] All other biological materials / reagents can be obtained from commercial sources.
[0029] 2.1 Establishment of mouse liver fibrosis model
[0030] After the animals were adaptively fed for one week, the mice were randomly divided into 2 groups, 8 in each group, 16 in total. The control group and the model group were respectively, and...
Embodiment 2
[0049] Example 2 Injecting mice with FXR adenovirus can significantly improve the symptoms of liver fibrosis
[0050] 1 Experimental materials
[0051] The adenovirus carrying FXR (Ad-FXR) was donated by Professor Frank J Gonzalez of the NIH Center in the United States and amplified by Bailingwei Biotechnology Co., Ltd. The control adenovirus (Ad-Ctrl) was designed, synthesized and amplified by the company;
[0052] Experimental mice were purchased from the Comparative Medicine Center of Yangzhou University;
[0053] Anti-FXR antibody was purchased from Abcam Company, and anti-GAPDH antibody was purchased from Bioworld Company.
[0054] All the other experimental materials are the same as in Example 1.
[0057] After the animals were adaptively fed for one week, the mice were randomly divided into 4 groups, 10 in each group, 40 in total. They were blank control group, FXR Adenovirus group, model ...
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Abstract
The present invention relates to the field of biomedicine. The present invention provides application of a farnesoid X receptor (FXR) expression interference reagent in preparation of anti-hepatic fibrosis drugs. Specifically, the present invention relates to application of FXR for treatment of hepatic fibrosis, by tail intravenous injection of the farnesoid X receptor (FXR) expression interference reagent (namely, an adenovirus carrying FXR plasmid) to mice, the expression level of the FXR in hepatocytes is significantly increased, CCl4-induced hepatic fibrosis can be significantly countered,hepatocyte morphology and structural integrity can be maintained, and serum transaminase level can be reduced. A new approach for clinical treatment of liver diseases especially hepatic fibrosis is provided.
Description
technical field [0001] The present invention relates to the field of biomedicine. Specifically, the present invention belongs to genemedicine in the field of biopharmaceuticals, and in particular relates to a gene therapy drug against liver fibrosis, that is, using a recombinant adenovirus carrying farnesoid X receptor (FXR) in the preparation of liver Application in drugs for the prevention and treatment of fibrotic diseases. technical background [0002] The incidence of liver diseases, especially viral hepatitis, fatty liverdisease, liver fibrosis and liver cancer, remains high worldwide. For example, the incidence rate of NAFLD among ordinary adults in Europe and America is 20-33%, and the incidence rate among obese people reaches 60-90%; the prevalence rate of ordinary adults in China is about 15% (Fan J G, Farrell G C. non-alcoholic fatty liverdisease in China. Journal of Hepatology, 2009, 50(1): 204-10.). Liver fibrosis (Fibrosis) is a pathological state, which ...
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