| Objectives:Diabetes mellitus(DM) can lead to a host of pathological alterations characterized by multiple organ dysfunctions, of which the diabetic nephropathies(DN) are a major cause of morbidity and mortality. However, there is no more effective measures to delay the development of diabetic nephropathy. This study aimed to investigate the effect of atorvastatin on the urinary protein and serum Rho A in type 2 diabetes mellitus patients and clarify a contribution of the atorvastatin in the effect and possible pathogenesis of diabetic nephropathy, finally to provide new therapies for clinical treatment of early diabetic nephropathy.Methods: From January 2015 to August 2015, a total of 76 patients with diabetes mellitus who were admitted to the second Hospital, Hebei Medical University, were enrolled in this study. They were then divided into the following 2 groups: 20 patients with simple diabetes mellitus(Group B), 56 patients with diabetic nephropathy(Group C). 20 healthy volunteers were selected as normal control group(Group A). All patients with diabetes received diabetes education and management, and the blood glucose of the patients were kept at the desired level. Fasting blood glucose(FBG), glycatedhemoglobin(Hb A1c), total cholesterol(TC), triglyceride(TG), urea nitrogenurea(BUN), creatinine(Cr), alanineaminotransferase(ALT), aspertate aminotransferase(AST), urinary albumin and creatinine ratio(ACR) in the three groups were determined respectively. The level of Rho A, TGFβ1 in serum and levels of TGFβ1, 8-OHd D in serum were determined by enzyme-linked immunosorbent assay. All the above indicators in the three groups were determined and compared respectively. Patients with diabetic nephropathy were divided into atorvastatin calcium treatment group(n=30, 20mg/d, was administered for three months, Group C1) and benazepril hydrochloride treatment group(n=26, 10 mg/d, was administered for three months, Group C2). In addition, it is necessary to give ezetimibe to the group C2 for three months. All the above indicators before and after the treatment in the two groups were determined and compared respectively. All statistical data were dealt with SPSS13.0, and P<0.05 was considered statistically significant.Results: 1 Baseline data analysis 1.1 Blood glucose level, blood lipids level, renal function and liver function index:Compared with the control group, the level of FBG, Hb A1 c, TC, TG in the diabetes group and diabetic nephropathy group increased markedly(P<0.01). But there was no significant difference in the above indicators between the two groups(P>0.05); there was no significant difference in the level of BUN, Cr, ALT and AST between the three groups(P>0.05). 1.2 The urine protein content:ACR in the diabetic nephropathy group increased significantly compared with the control group and the diabetes group(P<0.01); compared with the control group, there was no significant difference in ACR in diabetes group(P>0.05). 1.3 The level of Rho A and TGFβ1 in the serum: The level of Rho A and TGFβ1 in the serum of the diabetes group and diabetic nephropathy group increased significantly compared with the control group(24.92±4.04pg/ml and 13.48±6.62pg/ml vs. 7.12±12.24pg/ml, 6178.09±1096.54pg/ml and 3840.63±874.38pg/ml vs. 2065.49±498.51pg/ml, P<0.01). The level of Rho A and TGFβ1 in the serum of the diabetic nephropathy group was markedly higher than that of the diabetes group(24.92±4.04pg/ml vs. 13.48±6.62pg/ml, 6178.09±1096.54pg/ml vs. 3840.63±874.38pg/ml, P<0.01). 1.4 The level of TGFβ1 and 8-OHd G in the urine: The level of TGFβ1 and 8-OHd G in the urine of the diabetes group and diabetic nephropathy group increased significantly compared with the control group(367.44±43.64pg/ml and 196.16±65.74pg/ml vs. 80.43±32.09pg/ml, 450.57±99.68pg/ml and 292.13±89.99pg/ml vs. 151.74±61.04pg/ml, P<0.01). The level of TGFβ1 and8-OHd G in the urine of the diabetic nephropathy group was markedly higher than that of the diabetes group(367.44±43.64pg/ml vs. 196.16±65.74pg/ml, 450.57±99.68pg/ml vs. 292.13±89.99pg/ml, P<0.01). 2 The comparison between and within the two groups before and after the treatment: 2.1 The comparison between the two groups before and after the treatment: Before the treatment, compared with benazepril group, there was no significant difference in FBG, Hb A1 c,TC,TG, BUN, Cr,ALT, AST, ACR, and the level of Rho A and TGFβ1 in serum, TGFβ1 and 8-OHd G in urine in the Atorvastatin group(P>0.05); After the treatment, ACR and Hb A1 c in Atorvastatin group decreased significantly compared with benazepril group(9.22±4.22mg/mmol vs. 12.22±3.92mg/mmol, 8.04±1.1 vs. 6.7±0.91, P<0.01); after the treatment, the level of Rho A and TGFβ1 in serum, TGFβ1 and 8-OHd G in urine in Atorvastatin group decreased significantly compared with benazepril group(9.14±2.22pg/ml vs. 12.71±3.84pg/ml, 3924±684.55pg/ml vs. 4666.53±1028.3pg/ml, 140.96±30.11pg/ml vs. 225.83±98.5pg/ml, 112.31±55.46pg/ml vs. 216.96±35.58pg/ml, P<0.01); and there was no significant difference in FBG, TC, TG, BUN, Cr, ALT and AST between the two groups(P>0.05). 2.2 The comparison within the two groups before and after the treatment: For Atorvastatin group, after the treatment, Hb A1 c, TC and TG declined significantly P<0.01; but there was no significant difference in the level of BUN, Cr, ALT, AST compared with that before the treatment(P>0.05). For Atorvastatin group, after the treatment, ACR were reduced significantly(9.22±4.22mg/mmol vs. 17.17±6.82mg/mmol, P<0.01); the level of Rho A and TGFβ1 in serum, TGFβ1 and 8-OHd G in urine decreased significantly(9.14±2.22pg/ml vs. 25.02±3.6pg/ml, 3924±684.55pg/ml vs. 5956.18±1207.21pg/ml, 140.96±30.11pg/ml vs. 351.81±31.93pg/ml, 112.31±55.46pg/ml vs. 447.09±102.55pg/ml, P<0.01). For benazepril group, after the treatment, Hb A1 c, TC and TG declinedsignificantly P<0.01; but there was no significant difference in the level of BUN, Cr, ALT, AST compared with that before the treatment(P>0.05). For benazepril group, after the treatment, ACR were reduced significantly(12.22±3.92mg/mmol vs. 15.67±5.08mg/mmol, P<0.01); the level of Rho A and TGFβ1 in serum, TGFβ1 and 8-OHd G in urine decreased significantly(12.71±3.84pg/ml vs. 24.79±4.55pg/ml, 4666.53±1028.3pg/ml vs. 6434.13±909.67pg/ml, 225.83±98.5pg/ml vs. 385.48±48.74pg/ml, 216.96±35.58pg/ml vs. 454.59±98.11pg/ml, P<0.01). 3 Adverse effects Patients were not present gastrointestinal reactions such as nausea, vomiting, does not appear the unwell symptom such as muscle pain, edema, check liver function abnormality was not found. There were no adverse effects in the patients in Atorvastatin group.Conclusions: 1 High blood sugar can increase oxidative stress,enhance Rho A protein activity and raise the expression of TGFβ1 in renal of patients with type 2 diabetes, which may be involved in the formation and progress of type 2 diabetic nephropathy. 2 Atorvastatin can reduce urinary albumin in type 2 diabetes patients with early nephropathy, which has protection of renal function. This effect may be accomplished through inhibiting renal oxidative stress and the excessive activation of Rho A/ROCK pathway partly. |
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