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Objective:Blood-brain barrier is the key barrier of brain in the innate immune.It can prevent the harmful substances from the blood into the brain.In order to keep the brain in a relatively stable environment and maintain the normal function of the nervous system,it can also pump harmful substances or excess substances outside the brain selectively.Among them,brain microvascular endothelial cell tissue is a key part in the blood-brain barrier’s function.The number of the patients with central nervous system(CNS)diseases increased year by year.The therapeutic drug is usually inhibited by the blood-brain barrier and is difficult to work.Therefore,how to modify the drug and to make it easier to cross the blood brain barrier is the key point to cure CNS.At present,more than 95%research focus only on how nano drugs can enter the cell,the way and efficiency to enter the cell and the research of effect of nano drug etc.For the process of drug carrier in endocytosis,intracellular transport and release and regulation of research are rarely reported.Clathrin and P-glycoprotein are related protein in endocytosis and exocytosis with nano drug.Clathrin is located on the plasma membrane.It participates in endocytosis of some nutrients,and maybe the entry into the cell of some drugs.P-glycoprotein is located in the membrane of cerebral capillary endothelial cells.It can efflux drugs relying on ATP.Although there is a certain understanding of the cell in the inner swallow and efflux.But the process of the liposome drug is not clear.To solve the above problems,using colloidal gold liposome nano materials to trace liposome’s transport and regulation mechanism in brain microvascular endothelial cells,and study endocytosis,release,distribution and regulation mechanism of nano liposomes in brain microvascular.The solution of this problem can guide to construct reasonable drug carrier,and look forward to clarifing the molecular basis and mechanism of nano drug carriers across the BBB.This work has important theoretical and practical significance for the development and application of liposomes in the future.Results:For untreated cerebral microvascular endothelial cells,the cells incubated with colloidal gold liposomes can uptake of liposome colloidal gold,and with the extension of time,there are gold colloids in the plasma membrane,endoplasmic reticulum,Golgi apparatus and lysosomes in order,and finally colloidal gold liposome exports out of the cell.For cerebral microvascular endothelial cells treated by sodium azide,compared with untreated cells,the cells incubated with colloidal gold liposomes,cannot be observed liposome colloidal gold in them.For cerebral microvascular endothelial cells treated by reserpine,the cells incubated with colloidal gold liposomes,compared with untreated cells,colloidal gold liposome cannot export out of the cell.Conclusions:The uptake of liposomes in brain microvascular endothelial cells require clathrin’s participation.The excretion of liposomes from brain microvascular endothelial cells require P-glycoprotein’s participation.After colloidal gold liposome entering brain microvascular endothelial cells,it moves into the endoplasmic reticulum,Golgi apparatus and lysosomes in order.Finally colloidal gold liposome exports out of the cell.
Objective: Blood-brain barrier is the key barrier of brain in the innate immune. It can prevent the harmful substances from the blood into the brain. Order to keep the brain in a relatively stable environment and maintain the normal function of the nervous system. , it can also pump harmful substances or excess substances outside the brain selectively. Among them, brain microvascular endothelial cell tissue is a key part in the blood-brain barrier’s function. The number of the patients with central nervous system (CNS) diseases increased year by the year.The therapeutic drug is usually done by the blood-brain barrier and is difficult to work. Herefore, how to modify the drug and to make it easier to cross the blood brain barrier is the key point to cure CNS. At present, more than 95% research focus only on on nano drugs can enter the cell, the way and efficiency to enter the cell and the research of effect of nano drug etc. for the process of drug carrier in endocytosis, intracellular transport and release and regulation of research are rarely reported. Clathrin and P-glycoprotein are related proteins in endocytosis and exocytosis with nano drug. Clathrin is located on the plasma membrane. Particip participates in endocytosis of some nutrients, and maybe the entry into the cell of some drugs.P-glycoprotein is located in the membrane of cerebral capillary endothelial cells. It can efflux drugs relying on ATP .Although there is a certain understanding of the cell in the inner swallow and efflux.But the process of the liposome drug is not clear .To solve the above problems, using colloidal gold liposome nano materials to trace liposomes transport and regulation mechanism in brain microvascular endothelial cells, and study endocytosis, release, distribution and regulation mechanism of nano liposomes in brain microvascular. The solution of this problem can guide to construct reasonable drug carrier, and look forward to clarifying the molecular basis and mechanism of nano drug carriers across the BBB.This work has important theoretical and practical significance for the development and application of liposomes in the future. Results: For untreated cerebral microvascular endothelial cells, the cells incubated with colloidal gold liposomes can uptake of liposome colloidal gold, and with the extension of time, there are gold colloids in the plasma membrane, endoplasmic reticulum, Golgi apparatus and lysosomes in order, and finally colloidal gold liposome exports out of the cell. For cerebral microvascular endothelial cells treated by sodium azide, compared with untreated cells, the cells incubated with colloidal gold liposomes, can not be observed observed liposome colloidal gold in them. For cerebral microvascular endothelial cells treated by reserpine, the cells incubated with colloidal gold liposomes, compared with untreated cells, colloidal gold liposome can not export out of the cell. Conclusions: The uptake of liposomes in brain microvascular endothelial cells require clathrin’s participation.The excretion of liposomes from brain microvascular endothelial cells require P-glycoprotein’s participation. After colloidal gold liposomes entering brain microvascular endothelial cells, it moves into the endoplasmic reticulum, Golgi apparatus and lysosomes in order. Finally colloidal gold liposome exports out of the cell.