Study On The Mechanism Of EPO Alleviating Acute Kidney Injury By Promoting Kidney Lymphangiogenesis

Background:1.Acute kidney injury happens after being hit by trauma,infection,drug toxicity and other factors.Acute renal injury which has led to many patients becoming renal transplant recipient is also an inevitable blow for kidney transplant patients.In addition,it is also an important reason for shortening the life span of the graft.Therefore,strengthening the research on acute kidney injury can provide new targets for the diagnosis and treatment of it and protect health of patients.2.In recent years,with the discovery of a series of lymphatic markers,the research on lymphatic vessels has entered a fast lane.As an important tube for immune cells and fluids,lymphatic vessels play an important role in the pathological process of various acute organ injuries.At present,the research on lymphatic vessels in acute renal injury is still in the early stage,and the function of lymphatic vessels in acute renal injury is still controversial.Exploration of related regulatory mechanisms is needed.We hope to explore the changes of lymphatic vessels and its function after acute renal injury.3.EPO is an important hormone secreted by the kidney,which plays an important role in maintaining the normal level of red blood cells.In addition,EPO has many other functions,such as anti-inflammatory,anti-aging,promoting tissue repair,etc.These new functions make EPO have the potential to play an important protective role in acute kidney injury.As a commonly used drug in clinic,we hope to verify the protective effect of EPO on kidney injury,observe the related changes in inflammation and immunity of acute kidney injury after EPO intervention.Focus on this.,our research can provide evidence and theoretical basis for EPO in the prevention and treatment of acute kidney injury.Besides,we hope to promote the transformation of EPO’s new scene application,and provide new ideas and perspectives for EPO’s related research,especially in the field of acute kidney injury.Materials and methods:1.Construct renal ischemia-reperfusion model and folic acid acute kidney injury model.Use PCR,immunofluorescence and other techniques to observe inflammatory.2.Comparing the renal pathological and serological results of EPO group and control group to determine whether EPO is safe for the kidneys.Immunofluorescence was used to observe the effect of EPO on renal lymphatic vessels.QPCR was used to explore potential regulatory pathway genes.Changes in the spleen showed the side effects of EPO.3.Comparing the renal pathological and serological results of acute kidney injury mice with or without EPO intervention to determine whether EPO has a protective effect on AKI.Immunofluorescence and flow cytometry were used to detect renal immune cells.Infiltration changes were described,and q PCR technology was used to detect the levels of inflammatory factors,lymphatic markers and related pathway genes in the tissue.4.LYVE-1 antibody was used to explore the importance of lymphatic vessels in the protection of EPO’s acute renal injury.We described the immune infiltration of tissues by immunofluorescence technology,and detect the transcription of inflammatory factors,lymphatic vessel markers and related regulatory pathway genes in tissues by q PCR technology.5.In vitro experiments verify EPO can promote the proliferation of human lymphatic endothelial cells.And EPO concentration gradient experiment is used to confirm the best working concentration of EPO to stimulate lymphatic endothelial proliferation.The possible regulatory pathway EPOR-Akt pathway was verified by comparing the transcription level of EPOR and Akt phosphorylation between EPO-stimulated group and control group.Results:1.After acute kidney injury,the kidney is destroyed and kidney lymphangiogenesis happens.Immune infiltration intensifies and the level of inflammatory factors increases.Besides the transcription levels of VEGF-c and EPOR increase.2.EPO can promote lymphangiogenesis in the kidney and up-regulate the transcription levels of VEGF-C and EPOR in the tissue.The side effect of EPO promoting spleen enlargement is reversed after stopping the drug.3.The supplementation of exogenous EPO can alleviate acute kidney injury,reduce tissue immune infiltration,and promote the proliferation and repair of renal tubules.4.After the lymphatic vessels lose their function,the protective effect of EPO pretreatment on acute kidney injury is weakened,and the promotion effect of EPO on the proliferation and repair of renal tubules is weakened.5.EPO promotes the proliferation of human lymphatic endothelial cells through the EPOR-Akt pathway.Conclusion:1.EPO can safely and effectively reduce the damage of renal structure and function after acute kidney injury.The level of inflammatory factors and the infiltration of T cells and macrophages are reduced.Besides,EPO can enhance the proliferation and repair of kidney tubules after injury.2.EPO can alleviate acute kidney injury by promoting the lymphangiogenesis and expanding the lumen area.The mechanism may be that the proliferating lymphatic vessels enhance the drainage of immune cells and inflammatory factors,and effectively reduce the level of renal inflammation and immune infiltration after injury.3.EPO is expected to play an important role in the prevention and treatment of acute kidney injury through clinical transformation,protecting the damaged kidney and maintaining the health of patients.