| BackgroundDiabetic nephropathy(DN)is a clinical syndrome characterized by persistent proteinuria and progressive decline in renal function.It is a common secondary glomerular disease and has become the most common cause of end-stage renal disease.Inflammation plays a key role in the pathogenesis of DN and renal fibrosis,and interleukin-6(IL-6)is an important inflammatory factor,but its regulatory mechanism in DN is still unclear.IL-6 is not only regulated by classical signaling pathways,but also regulated by epigenetic mechanisms.Studies have found that histone modifications in epigenetic regulation play an important role in DN.Therefore,the relationship among IL-6 and histone modifications and renal fibrosis is worthy of further investigation.ObjectiveTo explore the relationship between the expression of IL-6 and histone deacetylase 4(HDAC4)in kidney tissue of type 2 diabetic rats and renal fibrosis,it is expected to provide a new strategy basis for the treatment of diabetic nephropathy.Methods56 healthy male SD rats,weighing 170-190 g,and about 7 weeks old.They were randomly divided into control group(Con group,n=28)and diabetic nephropathy group(DN group,n=28).The Con group had normal diet and water,and the DN group was pre-fed with high-fat and high-sugar feed for 6 weeks,and then intraperitoneally injected streptozotocin(STZ)at a dose of 40mg/kg.The blood glucose and blood glucose in the tail vein of the rats were measured at 72 hours after injection.Higher than 16.7mmol/L indicates that the establishment of the diabetes model is successful,and the rats whose blood glucose is not up to the standard have an additional injection of STZ(30mg/kg).The diabetic rats continued to be fed with high-fat and high-sugar feed for 4 weeks,and the ratio of urine microalbuminuria to creatinine was determined to be higher than 30mg/g,indicating that the model of diabetic nephropathy rats was successfully established.The urinary protein,urinary creatinine,urinary glucose and blood glucose values of each group of rats were measured regularly.After successful modeling,the Con group and DN group rats were killed in batches every 4 weeks(0,4,8,12 weeks),whichever was larger Mouse kidney tissues were stained with related pathology and IL-6,HDAC4,Transforming growth factor-1(TGF-β1)were stained with immunohistochemistry to detect the expression level,and finally the results were comprehensively analyzed and compared.Results1.General biochemical indicators: A total of 22 rats in the DN group were successfully modeled with diabetic nephropathy.During the entire feeding process,it was observed that the rats in the DN group showed typical symptoms of polydipsia,polyphagia,and polyuria,and the hair color was yellow and dull;Con The rats in the group were in good condition and gradually gained weight.During the experiment,the blood glucose level and urine microalbumin-creatinine ratio of the DN group were significantly higher than those of the Con group.At the 12 th week,the average blood glucose level of the DN group was maintained at(22.85±4.96)mmol/L,and the urine microalbumin-creatinine ratio was(80.67±12.69)mg/g(P<0.05).2.Pathological staining: The pathological staining of the kidney tissues of the two groups of rats was observed under a light microscope,and it was found that the renal interstitium,glomeruli and tubules of the Con group rats were not significantly abnormal;the renal tissues of the DN group rats were visible between the kidneys.The mass is scattered in the inflammatory cells,part of the glomerulus increases in volume,and part of the mesangial area of ? ? the glomerulus and stromal cells proliferate.3.Immunohistochemistry: The expression of IL-6 and HDAC in renal tissue under light microscope is mainly distributed in the renal tubules.TGF-β1 is expressed in renal tubules and glomeruli.The expression levels of IL-6,HDAC4 and TGF-β1 in the kidney tissue of rats in the DN group were higher than those in the Con group during the same period(P<0.05).4.There was no significant correlation between the expression of IL-6 and HDAC4 and TGF-β1 in rat kidney tissue.there was a significant positive correlation between HDAC4 and TGF-β1(r=0.736,P<0.05).5.Rat blood glucose,urine albumin and creatinine ratio are positively correlated with the expression of HDAC4 and TGF-β1 in kidney tissue(P<0.05).ConclusionInflammation is involved in the pathogenesis of DN rats.The increased expression of IL-6 in renal tissue may be related to the key enzyme HDAC4 of histone deacetylation.HDAC4 can promote the process of renal fibrosis in DN rats,anti-inflammatory and expression.Epigenetic regulation is expected to provide a new target for DN therapy. |
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