舒洛地特对早期糖尿病肾病的干预效应

目的观察舒洛地特对糖尿病早期肾病患者的疗效,为糖尿病肾病的治疗寻求新途径。方法60例2型糖尿病肾病患者,24 h尿白蛋白排泄率(UAER)30～300 mg,不伴有高血压,其中男30例,女30例,年龄43～70 a,糖尿病病程0.5～30 a。待代谢控制稳定后,维持原糖尿病治疗方案不变,随机分为常规治疗组、氯沙坦钾组(50 mg,po,qd),舒洛地特组(舒洛地特600 LSU,iv或im,bid,疗程4 wk;然后续惯250 LSU,po,bid,疗程8 wk),比较治疗3 mo前后指标变化。所检测指标包括UAER(于治疗前、后第4 wk测定1次)、血压、空腹血糖(FPG)、糖化血红蛋白(HbAlc)、空腹C肽、总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、丙氨酸转氨酶(ALT)、r-谷氨酞转移酶(r-GT)、尿素氮(BUN)、肌酐(Cr)、血液黏度、血细胞比容(Hct)、纤维蛋白原(FIB)、血浆纤溶酶原激活剂抑制物-1(PAI-1)、血浆内皮素(ET)、血清一氧化氮(NO)。结果常规治疗组用药前后UAER变化不明显,统计学分析无显著差异。氯沙坦钾组用药前后UAER从治疗前(90.33±35.56) mg·24 h~(-1)下降到治疗后的(58.76±33.21)mg·24 h~(-1);舒洛地特组UAER从(88.83±43.18)mg·24 h~(-1)下降到(56.64±32.96)mg·24 h~(-1)。用药前后比较,2组UAER差异均有高度统计学意义(P值均<0.01)。氯沙坦钾组治疗3 mo后UAER下降34.04%,舒洛地特组下降33.62%,2组间比较无显著性差异。氯沙坦钾组、舒洛地特组2组患者UAER随治疗时间的延长均呈逐渐减少趋势,治疗后2组UAER同常规治疗组比较,具有明显差异。舒洛地特组用药后,血清NO明显增高,PAI-1、FIB、ET等指标有一定程度的下降;氯沙坦钾组血浆ET水平在治疗后显著下降。3组DN患者用药前后FPG、HbAlc、TC、TG、HDL-C、LDL-C、ALT、r-GT、BUN、Cr、空腹C肽、Hct和血压等指标差异无统计学意义。结论舒洛地特能够减少微量白蛋白尿期2型糖尿病肾病患者的尿白蛋白排泄,延缓甚至逆转肾病进展,且用药时间越长,受益越大。

Effects of sulodexide on early diabetic nephropathy

AIM To observe the effect of sulodexide on early diabetic nephropathy , and to seek new treatment method for diabetic nephropathy. METHODS The treatment research was made within 60 cases of type 2 diabetic nephropathy patients (with 30 male, and 30 female aging from 43- 70 a), their urine albumin excretion rote (UAER) within 24 h was 30 - 300 rag, and non was accompanied by hypertension, the illness course of them was from 6 mo to 30 a. After the metabolic control was stabilized, the original treatment plan was maintained. The patients were divided randomly into 3 treatment groups: routine group,losartan group (50 mg po,qd), and sulodexide group (using 600 LSU,iv,or ira, bid, sulodexide for 4 wk; and then continuing with 250 LSU, po ,bid, for 8 wk), and compared the index changes after 3 mo treatment. The test index includesd: UAER (be tested every 4 wk before and after the treatments), BP, FPG,HbAlc, C peptide on an empty stomach, TC, TG, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), ALT, r-GT, BUN, Cr, blood viscosity, Hct, FIB, blood plasminogen activator inhibitor (PAI-1),endothelin (ET), serum nitric oxide(NO). RESULTS The results showed that the UAER change of routine group was not obvious, and the statistic analysis showed no obvious difference. The UAER of losartan group dropped from (90.33 ± after the use of this drug ( P values were both less than 0.01 ). After 3 mo treatment the UAER of losartan group dropped by 34.04%, while that of sulodexide group dropped by 33.62%, there was no obvious difference between these 2 groups. The UAER of these 2 groups decreased as the treatment was prolonged, and the after treatment UAER was obviously different from that of conventional treatment group. After applying the drag, and serum NO was obviously increased,blood viscosity, whole blood deoxidized viscidity, and index of PAI-1, FIB, ET, etc, all had certain decrement. The blood plasma ET level of losartan group dropped obviously after the treatment. However, there was no obvious change with the index like FPG, HbAIc,TC, TG, HDL-C, LDL-C, ALT, r-GT, BUN, Cr, C peptide on an empty stomach,Hct, and BP for these 3 groups. CONCLUSION Sulodexide can reduce the UAER of type 2 early diabetic nephropathy,and postpone or even reverse the development of nephropathy. The longer the drug is applied, the more the patient can benefit. The effect of sulodexide on diabetic nephropathy is realized through decreasing blood viscosity, PAI-1, FIB, and ET level in circulation, as well as increasing sertan NO. It can help maintain the selective permeability function of blood vessel wall, prevent various macro-molecule (for example albumin, fibrinogen, and lipoprotein) leak through the blood vessel wall;preserve the normal negative charge on blood vessel wall; and control cell multiplication as well as the afterward occurring function loss of blood vessel wall basement memberane, and extracellular matrix (ECM).