黄嘌呤氧化酶抑制剂对2型糖尿病肾病合并高尿酸血症患者血管内皮功能的影响

目的 探讨小剂量黄嘌呤氧化酶抑制剂对2型糖尿病肾病（DN）伴高尿酸血症（HUA）患者血管内皮功能及炎性反应的影响。方法 选择2018年1月至2019年5月解放军第967医院内分泌科收治的2型糖尿病肾病合并高尿酸血症患者96例，按随机数字表法分为非布司他组和别嘌醇组，每组各48例。两组患者统一接受糖尿病教育，均予以口服降糖药物或胰岛素控制血糖，同时严格低盐、低脂、优质低蛋白、低嘌呤糖尿病饮食等处理，适当运动，非布司他组在此基础上给予非布司他降尿酸治疗，别嘌醇组给予别嘌醇片降尿酸治疗，疗程为24周。观察两组患者治疗前后血尿酸（UA）、空腹血糖（FPG）、糖化血红蛋白（HbA1c）、总胆固醇（TC）、三酰甘油（TG）、低密度脂蛋白（LDL-C）、高密度脂蛋白（HDL-C）、尿素氮（BUN）、肌酐（Cr）、尿白蛋白/肌酐比值（UACR）、肌酐清除率（Ccr）、谷丙转氨酶（ALT）、超敏C反应蛋白（CRP）、白细胞介素-6（IL-6）、内皮素-1（ET-1）水平。治疗24周后UA水平与CRP、IL-6、ET-1水平的相关性。结果 治疗期间，两组患者均未出现明显的不良反应，均无脱落。治疗前，两组患者的性别、年龄、病程、各项生化指标等一般资料比较，差异均无统计学意义（P>0.05）。治疗24周后，两组患者UA、FPG、HbA1c、TC、TG、LDL-C、BUN、Cr、UACR、CRP、IL-6、ET-1均较治疗前均下降，Ccr、HDL-C较治疗前升高，差异均有统计学意义（P<0.05），ALT与治疗前比较，差异无统计学意义（P>0.05）。非布司他组治疗后24周UA、BUN、Cr、UACR、Ccr、CRP、IL-6、ET-1水平与治疗前的差值，与别嘌醇组差值相比，差异有统计学意义（P<0.05），余指标的差值组间比较，差异无统计学意义（P>0.05）。UA水平与CRP、IL-6、ET-1呈正相关（r=0.839、0.838、0.836，P<0.05）。结论 小剂量黄嘌呤氧化还原酶抑制剂降低2型糖尿病肾病伴高尿酸血症患者血尿酸水平的效果显著，对血管内皮功能、炎性反应均有较好改善作用。

Effects of Xanthine oxidase inhibitor on vascular endothelial function in patients with type 2 diabetic nephropathy complicated with hyperuricemia

Objective To investigate the effects of low-dose xanthine oxidase inhibitor on vascular endothelial function and inflammatory response in patients with type 2 DN with HUA. Methods Ninety-six patients with type 2 DN complicated with HUA admitted to the 967th hospital of P.L.A. from January 2018 to May 2019 were enrolled. The patients who met the criteria for admission were randomly divided into febuxostat group and allopurinol group, with 48 cases in each. The two groups of patients received diabetes education, and they were treated with oral hypoglycemic drugs or insulin to control blood sugar. The febuxostat group was treated with febuxostat for 24 weeks, and the allopurinol group was given allopurinol tablets. The levels of UA, FPG, HbA1c, TC, TG, LDL-C, HDL-C, BUN, Cr, UACR, Ccr, ALT, CRP, IL-6, ET-1 were observed before and after treatment in patients. Thecorrelation between UA level and CRP, IL-6, ET-1 levelswas assessed after 24 weeks of treatment. Results No patients fell off in either group. Before treatment, there was no significant difference in gender, age, duration of disease, and various biochemical indicators between the two groups (P>0.05). After 24 weeks of treatment, the levels of UA, FPG, HbA1c, TC, TG, LDL-C, BUN, Cr, UACR, CRP, IL-6, ET-1 were significantly lower than before(P<0.05), and the levels of Ccr and HDL-C were significantly higher(P<0.05). The difference between the levels of UA, BUN, Cr, UACR, Ccr, CRP, IL-6 and ET-1 in febuxostat group after treatment was statistically different from that in allopurinol group (P<0.05).The difference in the remaining indexes was not statistically significant between the two groups(P>0.05). UA level was positively correlated with CPR, IL-6 andET-1(P<0.05). Conclusions Low-dose xanthine oxidase inhibitors have significant effect on reducing blood uric acid levels in patients with type 2 DN complicated with HUA, which has a better effect on vascular endothelial function and inflammatory response.