| Objective:Diabetic nephropathy(diabetic nephropathy,DN)is one of the most common and severe chronic complications of diabetes,the mechanism of diabetic nephropathy is unclear,and the curative effect is not satisfactory.Clarifying the mechanism of diabetic kidney damage has an important clinical significance to explore the prevention and control measures.Rosiglitazone(Rosiglitazone)Margaret ketone compounds Thiazolidinediones(TZD use)is a synthetic PPAR gamma agonist(the ligand),which is a new type of insulin sensitization.Rosiglitazone can competitive with PPAR gamma(receptor)in combination with the activation,thus play a role of many physiological regulation.Foreign scholars based on a cellular level,found the PPAR gamma activation had a direct and indirect protection effect on diabetic nephropathy,the mechanism had not yet been elucidated.Autophagy(autophagy)is a kind of protective mechanism of clearing damaged cells or aging organelles or biological macromolecules.herefore,a new therapeutic target to combat diabetic nephropathy is required.Autophagy is a catabolic process that degrades damaged proteins and organelles inmammalian cells and plays a critical role inmaintaining cellular homeostasis.he accumulation of proteins and organelles damaged by hyperglycemia and other diabetes-related metabolic changes is highly associated with the development of diabetic nephropathy.Recent studies have suggested that autophagy activity is altered in both podocytes and proximal tubular cells under diabetic conditions.Autophagy activity is regulated by both nutrient state and intracellular stresses.Under diabetic conditions,an altered nutritional state due to nutrient excessmay interfere with the autophagic response stimulated by intracellular stresses,leading to exacerbation of organelle dysfunction and diabetic nephropathy.Mammals rapamycin target protein(m TOR)can integrate all sorts of signals inside and outside the cells,regulate cell growth and metabolism which is the center of molecules.All sorts of stimulation inside and outside cells such as energy,amino acids,glucose,insulin,growth factor,stress and hypoxia through the m TOR with other molecules to form compounds regulating protein translation,lipid synthesis,mitochondrial energy metabolism and physiological processes of cell growth and multiplication.The m TOR is at the centre of the life activities in the cell control status.Existing studies have shown that PPAR gamma can through regulating m TOR-autophagy signaling pathway to maintain articular cartilage metabolism balance,so whether PPAR gamma is through regulating m TOR-autophagy signaling pathways play a role in the DN?In this study,we use type 2 diabetic nephropathy rats model,studies the m TOR and the role of autophagy in diabetic nephropathy;Bying using Rosiglitazone and rapamycin intervention in diabetic model rats respectively,we observe the influence on diabetic nephropathy,discusses the role Rosiglitazone on diabetic nephropathy,and to study the pathogenesis and treatment of diabetic nephropathy open up new avenues.Methods:(1)the rats were divided into normal group and the control group,using STZ to manufactue model of type 2 diabetic nephropathy.Executed after 8 weeks when the diabetes rats model was sucessful,the general condition,blood,biochemical,pathological changes and autophagy activity and the change of the m TOR signaling pathways were observed in two groups of rats.(2)with rosiglitazone and rapamycin intervention respectively on model rats after 8weeks.Intervention in 4,8 weeks after the death of rat,fasting insulin,blood lipid,renal function,urinary microalbuminuria(Mau).Light microscopy glomerular morphology.Western blot method is to observe the renal LC3 and PS6 expression.Statistical analysis using SPSS17.0 statistics software.Results:(1)diabetic rats model was established successfully.Model of rat urine trace albumin increase;Light visible glomerular hypertrophy,mesangial membrane increased cell proliferation and mesangial matrix;Western blot found that diabetic rats kidney tissues of autophagy activity significantly decreased,characterized by LC3A/B;MTOR is activated,the performance P-S6 levels.(2)after the intervention on diabetic model rats,we found that rosiglitazone intervention can enhance autophagy activity and Inhibit m TOR signaling pathways.Rapamycin intervention can enhance the overall autophagy activity from the LC3A/B rise and m TOR signaling pathways suppression but rapamycin intervention does not reduce the kidney damage.Discuss:(1)the general function of autophagy in diabetic rat kidney tissues is reduced,the possible mechanisms through the activation of m TOR.(2)the intervention of rosiglitazone can inhibit m TOR activity,enhance autophagy activity,delay the progress of diabetic nephropathy.(3)after the Rapamycin intervention,autophagy activity is enhanced,but no obvious reduce diabetic rats kidney damage,which suggests there may be other mechanisms.This study explores the role of rosiglitazone in diabetic nephropathy,rosiglitazone control m TOR-autophagy pathway to protect of diabetic nephropathy,the new theory is of great importance for diabetic nephropathy prevention. |
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