| BackgroundDiabetic nephropathy is one of the most common microvascular diseases in diabetes.More and more studies have shown that inflammation and histone acetylation play an extremely important role in the occurrence and development of DN.IL-10 is currently recognized as an anti-inflammatory and immunosuppressive factor,involved in Inflammation and immune regulation;TGF-β1 As a pro-fibrotic inflammatory mediator,it plays a central role in the occurrence and development of DN renal fibrosis;HDAC4 As a key enzyme that mediates histone acetylation modification.Regarding whether there is an internal link between inflammation and histone acetylation Department is an issue worthy of attention.Therefore,this article takes inflammation and histone acetylation modification as the starting point to explore the expressions of IL-10,TGF-β1,and HDAC4 in DN rats and their clinical significance.ObjectiveTo explore the expression of IL-10,TGF-β1,and HDAC4 in rats with type 2 diabetic nephropathy,to analyze the relationship between IL-10,TGF-β1 and HDAC4,and to understand the inflammatory reaction and histone acetylation of DN in the early stage,which is expected to provide new therapeutic targets and strategies.Methods64 healthy male SD rats,6-8 weeks old,weighing 180-200 g,adaptive feeding for 1week Randomly divided into normal control group(NC group,n=32),diabetic nephropathy model group(DN group,n=32),The establishment of a diabetic nephropathy model induced by high-fat and high-sugar combined with 1% streptozotocin.The random blood glucose in the tail vein was measured at 72 hours >16.7mmol/L,and the urine protein was positive,which means that the model was successful.After successful modeling,rats were sacrificed at the end of 0,4,8 and 12 weeks,body weight,blood glucose,urine microalbumin and urine creatinine were measured before sacrifice.After execution,the kidney weight was calculated to calculate the kidney Index(KI=KW(mg)/BW(g)),parallel HE,PAS,PASM,Masson staining to observe the pathological changes of the kidney,Western blot method was used to detect the expression levels of IL-10,TGF-β1and Histone deacetyltransferase 4 in kidney tissue;heart blood was collected and used ELISA to detect the expression of the above indicators,and to analyze the relationship between IL-10,TGF-β1 and HDAC4.Results1.General indicators: The modelling rate of DN is as high as 78%.The blood glucose and urinary microalbuminuria-creatinine ratio of rats in the DN group are significantly higher than those in the NC group during the same period(P<0.01),until the end of the 12 weeks blood glucose of the DN group rats remained at 23.61±2.51mmol/L,the ratio of urine microalbumin and urine to creatinine was as high as 74.0±317.38mg/g;At the end of 8,12 weeks the body weight of rats in DN group was significantly lower than that in NC group at the same time(P<0.01);At the end of 8,12 weeks the KI of rats in the DN group was higher than that in the NC group during the same period(P<0.05,P<0.01).2.Kidney pathology under light microscope: there were no obvious pathological changes in renal tissue morphology and structure in NC group,and mild Mesangial segmental hyperplasia and interstitial inflammatory cell infiltration were seen in DN group at the end of 12 weeks.3.ELISA results showed that compared with the NC group during the same period,the expression levels of IL-10 and HDAC4 in the serum of the DN group at each stage were significantly increased(P<0.01);there was no significant expression of TGF-β1 in the serum of the two groups of rats at the end of the 0 week the difference,compared with the NC group at the same time,the expression of TGF-β1 in the serum of rats in the DN group at the end of the 4,8,and 12 weeks was significantly increased(P<0.01).4.The results of Western blot showed that compared with the NC group during the same period,the expression level of IL-10 in the kidney tissue of the DN group at the end of 0th,12 weeks was significantly increased(P<0.01),and the expression of IL-10 in the DN group at the end of 4,8 weeks was higher than that in the NC group during the same period(P<0.05);There was no significant difference in the expression of TGF-β1 in the kidney tissue of the two groups of rats at the end of 0th week.Compared with the NC group at the same time,the expression of TGF-β1 in the kidney tissue of the DN group at the end of 4,8 and 12 weeks was significantly increased(P<0.01);The expression of HDAC4 in the kidney tissue of rats in the DN group at the end of 0 week was higher than that of the NC group at the same period(P<0.05),Compared with the NC group at the same period,the expression of HDAC4 in the kidney tissue of the DN group at the end of 4,8 and 12 weeks was significantly increased(P<0.01).5.The expression of HDAC4 and TGF-β1 in the kidney tissue of DN rats was positively correlated(r=0.928,p<0.01),and the expression of HDAC4 and IL-10 was negatively correlated(r=-0.648,p<0.01);HDAC4 in the blood was correlated with The expression of TGF-β1 was positively correlated(r=0.638,p<0.01),the expression of HDAC4 and IL-10 was negatively correlated(r=-0.634,p<0.01).However,there was no significant correlation between the expression levels of IL-10 and TGF-β1 in kidney tissue and blood.ConclusionsIn the pathogenesis of DN,inflammation and fibrosis coexist,and histone acetylation is also involved.In the development of DN,histone acetylation modification is related to inflammation and fibrosis. |
PDF Full Text Request