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Diabetic nephropathy (DN) is one of the most serious complications of Diabetes mellitus (DM), and also an important cause of death. As one of the main clinical characteristic features, the proteinuria indicates the severity of DN. It predicts that using effective drug to control the proteinuria of DN is important to delay the early DN progression.Objective:In the animal experiment of this study, we applied RAS inhibitor and All-trans Retinoi Acid (ATRA) to clarify the effect on the changes, such as urinary albumin/urine creatinine (UAlb/UCr), kidney weight/body weight (KW/BW). In the clinical study we showed the comparison of the effect by using RAS inhibitor singly and ATRA plus RAS inhibitor. We predict the study could provide a theoretical basis and clinical evidence for the prevention and treatment of DN.Methods:Experimental animal was divided into four groups. 40 adult male wistar rats, adaptability keeping one week, and checked blood glucose (BG) level.Randomly selected 10 rats as control group (Group N, n=10), The remaining 30 rats were given a intraperitoneal injection one time with STZ (55mg/kg, Dissolved in pH4.2,0.1mol/L citrate-sodium citrate buffer, prepared fresh in ice bath), group N was given a injection of equivalent citrate-sodium citrate buffer. After 48 hours, tested the BG of each rat from tail vein. BG of group N is normal, and the remaining 30 rat blood sugar were higher than 16.7mmol/L. The 30 rats were randomly divided into three groups: DN model group (Group DN,n=10), DN+ ATRA treatment group (Group ATRA,n=10) and DN+ACEI treatment group (Group ACEI,n=10). ATRA was given to Group ATRA, 20mg/kg/d, by intragastric administration; Benazepril, 10mg/Kg/d, was given to Group ACEI by intragastric administration; distilled water to Group N. BW and BG were measured at the start and after four weeks when the experiment finished.Urine was collected at the end of the experiment, and then the rats were sacrificed, measured kidney weight, measured BG,BW, UAlb and UCr were assessed by ELISA, UAlb/UCr and KW/BW ratio were calculated. In clinical study, we selected 130 cases of DN patients, divided into 60 cases of early DN group and 70 cases of clinical DN group and each group was divided into ARB treatment group (Group ARB) and ATRA plus ARB group (Group ATRA plus ARB). Valsartan, 80mg/d, was given to Group ARB. Valsartan, 80mg/d and ATRA, 10mg/d was given to Group ATRA plus ARB. Using 24h urinary protein targets as the main observation, we analysed the treatment of early DN group and the clinical DN group by the application of ARB and ATRA plus ARB.Results:The changes of BG, BW, KW, KW/BW, UAlb/UCr in each group: BG of Group DN was significantly increased than Group N (P<0.01); treated by ATRA and ACEI, BG did not change significantly. BW of Group DN was decreased significantly compared with Group N (P<0.01); BW of Group ATRA and Group ACEI did not change significantly compared with Group DN. KW of Group DN was evidently increased than Group N (P<0.01); KW of the two treatment groups was decreased significantly compared with Group DN (P<0.01) and has no significant difference compared with Group N. KW/BW of Group DN was significantly increased than Group N (p<0.01); KW/BW of the two treatment groups decreased significantly compared with Group DN (P<0.05). UAlb/UCr of Group DN was significantly increased than Group N(P<0.01) and in the two treatment groups, UAlb/UCr decreased significantly compared with Group DN (P<0.01). In clinical study, compared with Group ARB, Group ATRA plus ARB got higher remission rate and reduced the proteinuria of DN more obviously.Conclusions:(1)ATRA could reduce the urinary albumin excretion in early DN rat to delay the early DN progression. (2)For the patients of early DN and clinical, ATRA plus ARB treatment could effectively reduce the DN of the urinary protein excretion, and more effectively than ARB monotherapy.
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