对氧磷脂酶-1和氧化低密度脂蛋白在2型糖尿病肾病中的作用

目的 探讨2型糖尿病（DM0对氧磷脂酶－1（PON－1）和氧化低密度脂蛋白（ox-LDL)与内皮细胞和血小板功能的关系,以及对糖尿病肾病（DN）发生、发展的影响。方法 用酚乙酸酯为底物的速率法测定91例2型DM患者血清PON－1,用ELISA法测定ox-LDL,同时测定血清一氧化氮（NO）、血管性假血友病因子（VWF）及血浆颗粒膜蛋白（GMP140）,并与正常人作对照,以24h尿白蛋白排泄率（UAER）将DM患者分成三组。结果 血清PON－1活性在2型DM三组中与对照组比较显著降低（P＜0．01）,血浆ox-LDL浓度则显著升高（P＜0．01）,二者在DM三组之间的差别有显著性（P＜0．05）。PON－1与尿白蛋白呈显著性负相关（P＜0．01）,ox-LDL则与之呈显著性正相关（P＜0．01）,二者之间呈负相关（P＜0．01）。PON－1与血NO呈正相关,与GMP 140呈显著负相关;ox-LDL与血NO呈负相关,与VWF、GMP140呈正相关,经Logistic回归分析,提示ox-LDL是DN的危险因子。结论 DM的高血糖和脂代谢紊乱造成的PON－1酶活性下降以及脂质过氧化物的堆积,使内皮细胞的完整性及功能受损,同时血小板的活化程度明显增强。它们的共同作用与DN的发生、发展密切相关。

The effects of paraoxonase-1 and oxidized low density lipoprotein on nephropathy in type-2 diabetes mellitus

OBJECTIVE: To explore the effect of paraoxonase-1 (PON-1) and oxidized low density lipoprotein (ox-LDL) in diabetic nephropathy (DN). METHODS: Serum PON-1 activity was measured by using phenyl acetate as a substrate and the concentration of plasma ox-LDL was determined by ELISA in 91 cases of type 2 diabetes mellitus (DM). Simultaneously, serum NO, VWF and GMP 140 were also determined. The patients of DM were divided into three groups according to urine albumine excretion rate (UAER) (DM I: UAER < 30 mg/24 h; DM II: UAER 30 approximately 300 mg/24 h; DM III: UAER > 300 mg/24 h) and matched with normal controls (NC). RESULTS: In the three groups of DM, PON-1 were markedly decreased and ox-LDL were obviously increased (P < 0.01). Both of their levels were different in the three groups of DM (P < 0.05). PON-1 were negatively correlated with ox-LDL (r = -0.467, P < 0.01). There were negative correlation between PON-1 and urine albumin (r = -0.697, P < 0.01), but ox-LDL was positively correlated with urine albumin (r = 0.747, P < 0.01). Serum nitrites (NO) level in DM I was significantly higher than that in NC, but the NO level in DM II and DM III was lower than that in DM I and NC. GMP 140 and VWF levels in all the 3 DM groups were higher than that in NC. PON-1 was positively correlated with NO (r(s) = 0.326, P < 0.01), and negatively correlated with VWF (r(s) = -0.365, P < 0.01). ox-LDL was negatively correlated with NO (r(s) = -0.196, P < 0.05), but positively correlated with VWF and GMP 140 (r(s) = 0.294, P < 0.05; r(s) = 0.669, P < 0.01 respectively). Logistic regression showed that ox-LDL was a dangerous factor for DN. CONCLUSION: PON-1, ox-LDL, NO, endothelial and platelet function are connected with DN; they affect one another and influence the occurrence and development of DN together.