Stable Nucleic Acid Lipid Nanoparticle-encapsulated SiRNA For The Treatment Of Non-alcoholic Steatohepatitis

The harm caused by nonalcoholic Steatohepatitis to the human body has caused more and more attention and research.Many scholars have focused their research on antioxidant and lipid metabolism,but ignored the role of inflammation in the progression of NASH disease.Studies have shown that the severity of NASH disease is positively related to inflammation.It can be seen that if the inflammation is effectively controlled,NASH disease can be effectively alleviated.HMGB1 is a DNAbinding nuclear protein and an important late-stage inflammatory factor,which is closely related to many inflammatory diseases.In non-alcoholic Steatohepatitis,a large amount of fat accumulated in the liver can cause lipid peroxidation,which leads to damage and apoptosis of liver cells.Apoptosis releases a variety of cytokines while activating liver macrophages,and recruits a large number of bone marrow-derived macrophages to the liver.HMGB1 released by macrophages is a molecular model related to prototype damage.In vivo(such as TLRs,RAGE)combined with activation of signal pathways such as NF-κB to mediate inflammatory responses,may promote the progression of NASH disease,leading to disease deterioration.In this study,experiments showed that the content of HMGB1 in liver parts of NASH mice is increased and is positively related to the disease.After that,we successfully constructed a siRNA delivery system(HMGB1-siRNA @ SNALP-mannose)targeting liver macrophages for Silence the expression of HMGB1.The experimental results show that HMGB1-siRNA @ SNALP-mannose can effectively target macrophages through the mannose receptor and can effectively silence the expression of HMGB1.The experimental results show that silencing the expression of HMGB1,NASH Hepatic lobular inflammation and bullous steatosis in the liver of mice were effectively alleviated,providing a new idea for the treatment of NASH disease in the future.