糖尿病视网膜病变患者血清同型半胱氨酸、维生素B12及叶酸与氧化应激的关系

Correlation of serum homocysteine,vitamin B12 and folic acid with oxidative stress in patients with diabetic retinopathy

目的分析糖尿病视网膜病变(diabetic retinopathy,DR)患者血清中同型半胱氨酸(homocysteine,Hcy)、维生素B12(vitamin B12,Vit B12)、叶酸与氧化应激水平的变化,并探讨它们之间的关系。方法选取我院2型糖尿病(type 2 diabetes,T2DM)患者140例,所有患者均行眼底镜检查、眼底荧光素血管造影及眼底照相检查,并根据中华医学会眼底病学组诊断及分期标准,将其分为无糖尿病视网膜病变(non-diabetic retinopathy,NDR)患者75例(NDR组),非增生型糖尿病视网膜病变(nonproliferative diabetic retinopathy,NPDR)患者37例(NPDR组),增生型糖尿病视网膜病变(proliferative diabetic retinopathy,PDR)患者28例(PDR组)。另选取我院体检中心体检合格,无血糖及糖化血红蛋白异常者70例为正常对照组。分别检测每组患者血清Hcy、Vit B12、叶酸、超氧化物歧化酶(superoxide dismutase,SOD)、丙二醛(malondialdehyde,MDA)、还原型谷胱甘肽(reduced glutathione,GSH)水平。并将NPDR组患者随机分为A组18例、B组19例,A组给予口服胰激肽原酶肠溶片,B组给予Vit B12+口服叶酸加胰激肽原酶肠溶片,分别治疗1个月后检测两组患者血清Hcy、Vit B12、叶酸、SOD、MDA、GSH水平。结果 NDP组、NPDR组、PDR组与正常对照组血清Hcy和MDA含量总体比较差异均有统计学意义(均为P=0.000),其中NDR组、NPDR组、PDR组Hcy、MDA水平均依次增高,且均明显高于正常对照组(均为P<0.05);NDP组、NPDR组、PDR组与正常对照组血清Vit B12、叶酸、SOD、GSH含量总体比较差异均有统计学意义(均为P=0.000)。其中NDR组、NPDR组、PDR组Vit B12、叶酸、SOD、GSH水平均依次降低,且均明显低于正常对照组(均为P<0.05)。治疗1个月后,A组患者血清Hcy、MDA、Vit B12、叶酸、SOD、GSH含量较治疗前均无明显变化(均为P>0.05);B组患者血清Hcy、MDA较治疗前均显著降低(均为P<0.05),血清Vit B12、叶酸、SOD、GSH含量较治疗前均显著升高(均为P<0.05),且B组治疗后血清Hcy、MDA含量均明显低于A组(均为P<0.05),Vit B12、叶酸、SOD、GSH含量均明显高于A组(均为P<0.05)。血清Hcy与MDA水平呈正相关(r=0.79,P<0.05),与Vit B12、叶酸、SOD、GSH水平均呈负相关(r=-0.61、-0.54、-0.43、-0.57,均为P<0.05)。结论 DR患者血清Vit B12、叶酸水平降低,同时伴随Hcy水平升高,氧化应激反应增强。联合应用Vit B12、叶酸治疗有助于降低DR患者血清Hcy水平及氧化应激反应。

Objective To analyze changes in serum homocysteine（ Hcy）,vitamin B12（ Vit B12） and folic acid as well as the association with oxidative stress in patients with diabetic retinopathy（ D R）. Methods Totally 140 patients with type 2 diabetes（ T2 D M） in our hospital were selected,and underw ent fundoscopy,fundus fluorescein angiography,and photograph examination. And according to the diagnosis from Chinese Medical Association Fundus D isease Group,the subjects were divided into 75 patients with non-diabetic retinopathy（ ND R group）,37 patients with nonproliferative diabetic retinopathy（ NPD R group）,and 28 patients with proliferative diabetic retinopathy（ PD R group）. Additional 70 patients,no blood sugar and abnormal hemoglobin,who received physical examination in our hospital were collected as normal control group. Then the levels of serum homocysteine（ Hcy）,vitamin B12（ Vit B12）,folic acid,superoxide dismutase（ SO D）,malondialdehyde（ MD A）,and reduced glutathione（ GSH） were detected in each group. Then,the patients in the NPD R group was randomly divided into group A（ 18 patients） and group B（ 19 patients）,and the former group was given orally with pancreatic kininogenase,and group B received Vit B12 plus folic acid plus pancreatic kininogenase. After one month of treatment,the serum levels of Hcy,Vit B12,folic acid,SO D,M DA,and GSH were measured in the two groups. Results There were significant differences in the serum Hcy and MDA levels betw een the four groups（ all P = 0. 000）. The levels of both Hcy and MDA in the NDR group,N PDR group,and PDR group increased in turn and were significantly higher than those in the normal control group（ all P〈0. 05）. There were statistically significant differences in the serum Vit B12,folic acid,SO D,and GSH levels among the four groups（ all P = 0. 000）. The levels of Vit B12,folic acid,SO D,and GSH in the NDR group,N PDR group,PDR group decreased in turn and were significantly low er than those in the normal control group（ all P〈0. 05）. After one month of treatment,the levels of serum Hcy,M DA,Vit B12,folic acid,SO D,and GSH in group A did not significantly changed when compared with before treatment（ all P〈0. 05）; the serum Hcy and MDA levels in group B were significantly low er than before treatment（ all P〈0. 05）,serum Vit B12,folic acid,SO D,GSH levels were significantly higher than before treatment（ all P〈0. 05）,and serum levels of Hcy and MDA in group B after treatment were significantly low er than those in group A（ all P〈0. 05）,Vit B12,folic acid,SO D,and GSH levels were significantly higher than those in group A（ all P〈0. 05）. There was a positive correlation betw een serum Hcy and MDA level（ r = 0. 79,P〈0. 05） and negative correlation with Vit B12,folic acid,SO D,and GSH levels（ r =-0. 61,-0. 54,-0. 43,-0. 57,all P〈0. 05）. Conclusion Serum Vit B12 and folic acid levels decreased,accompanied by increased Hcy level,and enhanced oxidative stress. Combination therapy with Vit B12 and folic acid can decrease serum Hcy levels and alleviate oxidative stress responses in patients with DR.