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目的观察不同剂量二肽基肽酶Ⅳ抑制剂磷酸西格列汀对早期糖尿病肾病患者的肾脏保护作用。方法120例糖尿病肾病Ⅲ期患者随机分为试验组1、试验组2和对照组,每组40例。所有患者均给予氯沙坦钾片+二甲双胍缓释片治疗,4周后,试验组1加用磷酸西格列汀片50 mg,1次/d;试验组2加用磷酸西格列汀片100 mg,1次/d;对照组加用格列齐特缓释片30 mg,2次/d。结果治疗后,3组的体重指数、FPG、2h PG、Hb A1c至第24周均较治疗前显著下降(P<0.05)。治疗后试验组1、试验组2的m ALB、尿蛋白肌酐比值、血清胱抑素C均显著低于对照组同一时间点相应水平(P<0.05),试验组2较试验组1下降更加明显(P<0.05)。3组的hs-CRP、IL-6、TNF-α、NF-κB p65磷酸化水平均较治疗前显著下降,试验组下降更加明显(P<0.05)。相关分析显示尿微量白蛋白水平与体重指数、FPG、2h PG、Hb A1c无明显相关性(P>0.05),与hs-CRP、IL-6、TNF-α、NF-κB均呈显著正相关(P<0.01)。结论磷酸西格列汀有独立于降糖作用之外的肾脏保护作用,机制可能为磷酸西格列汀通过抑制机体的炎症状态,减少炎症因子的释放,从而进一步改善肾脏的炎症损伤,达到肾脏保护作用,且其疗效呈剂量依赖性。
Objective To observe the protective effects of different doses of dipeptidyl peptidase IV inhibitor sitagliptin on patients with early diabetic nephropathy. Methods One hundred and twenty patients with stage Ⅲ diabetic nephropathy were randomly divided into experimental group 1, experimental group 2 and control group, with 40 cases in each group. All patients were given losartan potassium tablets + metformin sustained-release tablets after treatment, 4 weeks after the test group 1 plus sitagliptin phosphate tablets 50 mg, 1 / d; test group 2 plus sitagliptin phosphate tablets 100 mg once a day, while in the control group, gliclazide 30 mg twice daily was added. Results After treatment, body mass index, FPG, 2h PG, Hb A1c in the three groups were significantly decreased compared with those before treatment (P <0.05). After treatment, the levels of m ALB, urinary creatinine and serum cystatin C of experimental group 1 and experimental group 2 were significantly lower than those of the control group at the same time points (P <0.05), and the decrease of experimental group 2 was more obvious than that of experimental group 1 (P <0.05). The phosphorylation levels of hs-CRP, IL-6, TNF-α and NF-κB p65 in 3 groups decreased significantly compared with that before treatment, and the decrease was more obvious in experimental group (P <0.05). Correlation analysis showed that urinary microalbumin level had no significant correlation with body mass index, FPG, 2h PG and Hb A1c (P> 0.05), but had significant positive correlation with hs-CRP, IL-6, TNF- (P <0.01). Conclusions Sitagliptin phosphate has renal protection independent of hypoglycemic effect. It may be that sitagliptin phosphate inhibits the inflammatory state of the body and reduces the release of inflammatory cytokines, thereby further improving the renal inflammatory injury and reaching the kidney Protective effect, and its efficacy in a dose-dependent manner.