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目的观察应用硫辛酸治疗前后早期糖尿病肾病(DN)患者尿足细胞标志蛋白(PCX)和血浆血管内皮生长因子(VEGF)浓度的变化,探讨硫辛酸对肾小球足细胞的保护机制。方法 118例2型糖尿病患者根据24 h尿白蛋白排泄率(UAER)分为单纯糖尿病组58例和微量组60例,微量组再随机分为常规治疗组(降糖、优质低蛋白饮食和对症治疗)和硫辛酸组(常规治疗基础上加用硫辛酸600 mg,静脉滴注,每日1次,14 d为一个疗程),每组30例。另选60例健康体检者设为正常对照组。比较各组血糖、血脂、肾功能、UAER、血VEGF等指标,以尿足细胞标志蛋白-尿肌酐比(UPCR)表达尿PCX水平,分析UPCR和血VEGF与其他指标的相关性。观察治疗中不良反应的发生情况,微量组患者治疗后各项指标的变化。结果单纯糖尿病组和微量组患者空腹血糖、糖化血红蛋白、UPCR、血VEGF及丙二醛(MDA)水平高于正常对照组,超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)水平低于正常对照组(P<0.01)。微量组患者尿素氮、血肌酐、UAER、血VEGF和MDA水平高于单纯糖尿病组,SOD和GSH-Px水平低于单纯糖尿病组(P<0.05或P<0.01)。UPCR与UAER、MDA、VEGF正相关,与SOD、GSH-Px负相关(P<0.01)。血VEGF与UPCR、UAER、MDA正相关,与SOD、GSH-Px负相关(P<0.01)。治疗后,硫辛酸组患者UAER、UPCR、血VEGF及MDA降低,且低于常规治疗组(P<0.01);SOD和GSH-Px增高,且高于常规治疗组(P<0.01)。所有患者治疗期间均未发生明显不良反应。结论硫辛酸可能通过减少尿PCX排泄,下调血浆VEGF的表达,对早期DN患者肾小球足细胞起到一定的保护作用。
Objective To observe the changes of urinary podocyte marker protein (PCX) and plasma vascular endothelial growth factor (VEGF) levels in patients with early diabetic nephropathy (DN) before and after lipoic acid treatment and to explore the protective mechanism of lipoic acid on glomerular podocytes. Methods 118 patients with type 2 diabetes mellitus were divided into two groups according to their 24-hour urinary albumin excretion rate (UAER): 58 cases in simple diabetic group and 60 cases in trace group. The patients in control group were randomly divided into routine treatment group (hypoglycemic, high-quality low-protein diet and symptomatic Treatment) and lipoic acid group (conventional treatment based on the use of lipoic acid 600 mg, intravenous infusion, once daily, 14 d for a course of treatment), 30 cases in each group. Another 60 healthy subjects were set as normal control group. Urinary PCX levels were analyzed by urinary podocyte marker-urine creatinine ratio (UPCR), and the correlation between UPCR and serum VEGF and other indicators was analyzed. Blood glucose, blood lipid, renal function, UAER and serum VEGF were compared between groups. Observed the incidence of adverse reactions in treatment, trace group of patients after treatment of various indicators of change. Results The levels of fasting blood glucose, glycosylated hemoglobin, UPCR, blood VEGF and malondialdehyde (MDA) in the patients with simple diabetes mellitus and patients in the trace group were higher than those in the normal control group, the superoxide dismutase (SOD) and the glutathione peroxidase GSH-Px) levels were lower than the normal control group (P <0.01). The blood urea nitrogen, serum creatinine, UAER, serum VEGF and MDA in trace group were higher than those in simple diabetic group, and the levels of SOD and GSH-Px were lower than those in simple diabetic group (P <0.05 or P <0.01). UPCR was positively correlated with UAER, MDA and VEGF and negatively correlated with SOD and GSH-Px (P <0.01). Serum VEGF was positively correlated with UPCR, UAER and MDA and negatively correlated with SOD and GSH-Px (P <0.01). After treatment, UAER, UPCR, blood VEGF and MDA were decreased in patients with lipoic acid group and lower than those in the conventional treatment group (P <0.01). The SOD and GSH-Px levels were increased and were higher than those in the conventional treatment group (P <0.01). No significant adverse reactions occurred in all patients during treatment. Conclusion Lipoic acid may protect glomerular podocytes in early stage DN patients by decreasing urinary PCX excretion and decreasing plasma VEGF expression.