| Objective: Diabetic nephropathy is the most common and the most serious microvascular complications caused by diabetes and also one of the most important causes of death in diabetic patients. The pathogenesis of diabetic nephropathy is quite complicated, and there are no clinically effective steps to prevent its occurrence and progress. The purpose of this study is to investigate protection effects of fasudil on kidneys through the exploration of the effects of fasudil on Smad1 level in the blood and urine and albumin of type 2 diabetes patients with early diabetic nephropathy, thereby proposing new ways to the prevention and control of diabetic nephropathy.Methods: Sixty-two type 2 diabetes patients with early diabetic nephropathy hospitalized from January 2015 to December 2015 in endocrinology department of our hospital were selected as the microalbuminuria group, 20 outpatients with type 2 diabetes but no acute or chronic complications as the diabetes group, and 20 healthy volunteers as the control group. 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), glycated hemoglobin(Hb A1c), total cholesterol(TC), triglyceride(TG), urea nitrogen(BUN), creatinine(Cr), alanine aminotransferase(ALT), aspertate aminotransferase(AST), urinary microalbumin(MALB), urinary albumin and creatinine ratio(ACR) in the three groups were determined respectively; double antibody sandwich ABC-ELISA method was applied to determine the Smad1 level in the blood and urine of the three groups, and all the indicators in the three groups were analyzed. Patients of microalbuminuria group were randomly subdivided into two groups which were treated with alprostadil group(30 cases) and fasudil group(32 cases), respectively. For the former group, besides the conventional treatment, 10μg alprostadil in the drip chamber was administered for 14 days with once per day; for the latter group, 30 mg fasudil hydrochloride with 100 ml nomal saline solution was administered through intravenous injection for 14 days with twice per day. All the above indicators and platelet aggregation rate(PAg R) before and after the treatment in the two groups were determined and compared respectively.Results:1 The comparison between the three groups at baseline1.1 Blood glucose, blood lipids, 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 microalbuminuria 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: MALB content and ACR in the microalbuminuria 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 MALB and ACR in diabetes group(P>0.05).1.3 The level of Smad1 in the blood and urine: The level of Smad1 in the blood and urine of the microalbuminuria group and diabetes group increased significantly compared with the control group(83.49±4.54pg/ml and 40.42±2.46pg/ml vs 20.77±3.13pg/ml, 65.61±4.50pg/ml and 21.35±2.06pg/ml vs 10.12±1.61pg/ml, P<0.01); the level of Smad1 in the blood and urine of the microalbuminuria group was markedly higher than that of the diabetes group(83.49±4.54pg/ml vs 40.42±2.46pg/ml, 65.61±4.50pg/ml vs 21.35±2.06pg/ml,P<0.01).1.4 Correlation analysis: The level of Smad1 in the urine was positively correlated with ACR(r=0.847, P<0.01); there’s no correlation between the level of blood Smad1 and ACR(r=0.179, P>0.05).2 The comparison between and within the two groups before and after the treatment2.1 The comparison between the two groups before and after the treatment: Before the treatment, compared with alprostadil group, there was no significant difference in FBG, Hb A1 c, TC, TG, BUN, Cr, ALT, AST, PAg R, MALB, ACR, and the level of Smad1 in the blood and urine in the fasudil group(P>0.05); after the treatment, MALB and ACR in fasudil group decreased significantly compared with alprostadil group(14.46±3.09mg/L vs 38.55±3.83mg/L, 1.84±0.36mg/mmol vs 3.90±0.30mg/mmol, P<0.01); after the treatment, the level of Smad1 in the blood and urine in fasudil group decreased significantly compared with alprostadil group(39.26±3.86pg/ml vs 81.73±5.39pg/ml, 16.32 ± 1.99pg/ml vs 63.58±5.34pg/ml, P<0.01); PAg R in alprostadil group decreased significantly compared with fasudil group(60.89±4.57% vs 74.09±5.85%, 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 each group before and after the treatment: For fasudil group, after the treatment, MALB and ACR declined significantly(14.46±3.09mg/L vs 121.48±8.70mg/L, 1.84±0.36mg/mmol vs 8.26±0.79mg/mmol, P<0.01); the level of Smad1 in the blood and urine declined significantly(39.26±3.86pg/ml vs 84.10±4.28pg/ml, 16.32±1.99pg/ml vs 66.28±4.03pg/ml, P<0.01); PAg R decreased markedly(74.09±5.85% vs 87.10±4.07%, P<0.01); but there was no significant difference in the level of FBG, TC, TG, BUN, Cr, ALT, AST, systolic blood pressure(SBP) and diastolic blood pressure(DBP) compared with that before the treatment(P>0.05). For alprostadil group, after the treatment, MALB and ACR were reduced significantly(38.55±3.83mg/L vs 118.46±13.31mg/L, 3.90±0.30mg/mmol vs 8.04±0.93mg/mmol, P<0.01); there was no significant difference in the level of Smad1 in the blood and urine(P>0.05); PAg R was reduced significantly(60.89±4.57% vs 88.05±3.60%, P<0.01); there was no significant difference in the level of FBG, TC, TG, BUN, Cr, ALT, AST, SBP and DBP compared with that before the treatment(P>0.05).3 Adverse effectsPain and flush occurred at the intravenous injection site of three patients in alprostadil group and the pain eased as the injection speed slowed down. There were no adverse effects in the patients in fasudil group.Conclusion:1 For healthy people, patients with type 2 diabetes and type 2 diabetes patients with early diabetic nephropathy, the chang of Smad1 level in the blood and urine and the correlation analysis between Smad1 and ACR in the urine suggests maybe the involvement of Smad1 protein in the occurrence and development of type 2 diabetic nephropathy.2 Fasudil, as ROCK specific inhibitors, can effectively reduce the level of Smad1 in the blood and urine in type 2 diabetes patients with early diabetic nephropathy and reduce urinary albumin, which has a protective effect on diabetic nephropathy. And there was no noticeable adverse effects for the clinical application of fasudil. |
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