Application of macrophage-targeting RIPK1 and RIPK1 inhibitor in screening and preparing liver injury diagnosis and treatment medicine

Abstract

The invention discloses application of macrophage-targeting RIPK1 and an RIPK1 inhibitor in screening and preparing a liver injury diagnosis and treatment medicine RIPK1 inactivated mouse bone marrow is transplanted into a normal C57 mouse to construct a non-alcoholic fatty liver, cirrhosis and hepatic fibrosis model, a result shows that the liver function of the mouse with transplanted RIPK1 inactivated bone marrow is obviously superior to that of a mouse with transplanted C57 mouse bone marrow, the contents of glutamic-pyruvic transaminase and triglyceride in serum are obviously reduced, a lipid component pathological staining result shows that the mouse with transplanted RIPK1 inactivated bone marrow can obviously relieve fatty liver lesion and significantly reduce lipid accumulation, and it is found that RIPK1 inactivation can significantly reduce inflammation and death of palmitic acid-induced bone marrow macrophages. A macrophage-targeting RIPK1 active site can be used as a medicine target for screening and treating liver injury diseases such as fatty liver, cirrhosis and hepatic fibrosis, and the RIPK1 inhibitor can be used for preparing the medicine for treating the liver injury diseases.

Description

technical field [0001] The invention belongs to the technical field of gene function and application, and relates to a receptor interacting serine / threonine kinase 1 (RIPK1) and its inhibitor in the screening and preparation of drugs for diagnosis and treatment of liver damage Applications. Background technique [0002] Nonalcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterized by fatty degeneration and fat accumulation in hepatic parenchymal cells without a history of excessive alcohol consumption. The disease spectrum varies with the progress of the disease, including Simple fatty liver, nonalcoholic steatohepatitis (NASH), cirrhosis and even hepatocellular carcinoma. NAFLD is strongly associated with obesity, metabolic syndrome, and type 2 diabetes, and is considered a major cause of end-stage liver failure. [0003] Many patients with NAFLD develop a more inflammatory subtype—nonalcoholic steatohepatitis (NASH)—and advanced liver fibrosis ...

AI Technical Summary

Problems solved by technology

Studies have confirmed that the use of Nec-1 to inhibit RIPK1 kinase activity can reduce cell death and inflammation, and play an important role in some inflammatory and necrotic diseases (Takahashi N et al.2012), but in non-alcoholic fatty liver, liver fibrosis There are no related studies in the diseases of liver cancer and liver cirrhosis

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