枸杞多糖对糖尿病大鼠血糖、血脂及血-视网膜屏障通透性的影响

Effects of lycium bararum polysaccharides on blood glucose, blood fat and blood-retinal barrier in diabetic rats

背景糖尿病视网膜病变（DR）的特征是毛细血管闭锁、微循环障碍和局部缺血性视网膜新生血管形成，其确切的发病机制尚不十分清楚。目的观察枸杞多糖（LBP）对糖尿病（DM）大鼠血糖、血脂、血一视网膜屏障通透性的影响，探讨LBP对DR的保护作用及机制。方法SD大鼠54只，按随机数字表法随机分为3组，每组18只。其中36只大鼠尾静脉注射45mg／kg链脲佐菌素（STZ）建立DM模型，72h后血糖〉16．7mol／L、尿糖阳性者为造模成功。成模后第2天LBP治疗组给予200mg／（kg·d）LBP灌胃，DM组给予等量生理盐水灌胃，其他18只正常鼠为正常对照组。各组大鼠造模后4、8、12周抽取心脏血检测血糖、甘油三酯和总胆固醇水平，获取视网膜组织，用伊文思蓝渗漏实验检测视网膜血管的渗透性。结果各时间点DM组和LBP治疗组大鼠的血糖水平均高于正常对照组。4、8、12周时LBP治疗组大鼠的血糖水平明显较同时间点DM组明显下降，下降幅度分别为57％、40％、36％，差异均有统计学意义（P〈0．01）。DM组大鼠各时间点甘油三酯浓度明显高于正常对照组，差异均有统计学意义（P〈0．01），LBP治疗组在4周、8周时甘油三酯的浓度与正常对照组比较差异均无统计学意义，而12周时高于正常对照组，差异有统计学意义（P〈0．01）。DM组大鼠在8周、12周时血液中的总胆固醇浓度明显高于正常对照组，差异均有统计学意义（P〈0．01），而LBP治疗组在各时间点与正常对照组比较差异均无统计学意义（P〉O．05）。造模后4、8、12周大鼠视网膜血管渗透性增加，DM组伊文思蓝的渗透量分别为（26．23±2．00）、（29．78±1．78）、（34．08±3．03）μg／g，明显高于正常对照组的（12．34±4．30）、（12．76±2．11）和（12．45±4．40）μg／g，差异均有统计学意义（P〈0．01），各时间点LBP治疗组伊文思蓝的渗透量明显低于DM组，差异均有统计学意义（P〈0．01）。伊文思蓝的渗透量与血糖、甘油三酯的浓度变化均呈高度正相关（r=0．896、0．859，P=0．000），与总胆固醇的浓度变化呈显著正相关（r=0．770，P=0．000）。结论LBP可降低DM大鼠血糖及血脂水平，抑制DM大鼠血一视网膜屏障通透性的增加。

Background The characters of diabetic retinopathy （DR） include capillary occlusion, microcirculation disturbance and retina neovascularization near ischemic areas of the retina. The pathogenic mechanism is still incompletely clear,but the primary mechanism of DR is the change of permeability of retinal blood capillary. Objective The aim of this study was to investigate the effect of lyeium bararum polysaceharides（LBP） on the blood glucose, blood fat and permeability of blood-retinal barrier in diabetic rats. Methods Fifty-four clean adult SD rats were randomized into 4 groups. The diabetes mellitus models were created in 36 SD rats by injection of 45 mg/kg streptozotocin （STZ） via caudal vein. The rats with the blood glucose 〉 16.7 mol/L were defined as the diabetic mellitus in 72 hours after injection. LBP of 200 rag/（ kg ~ d） was intragastriccally administered in 18 models once a day in LBP group,and equal volume of normal sodium was used at the same way in 18 models in DM group, and 18 normal rats were as normal control group. The rats were killed in 4,8 and 12 weeks respectively for the detect of blood glucose level, triglyceride, total cholesterol. The retina tissue were isolated for the quantification of vascular permeability using Evans blue method. Results The blood glucose level was significantly elevated in the DM group and LBP group compared with normal control group,and that in LBP group was obviously declined in comparison with the DM group with a 57% , 40% , 36% fall off in 4,8, 12 weeks respectively, showing a statistically significant differences（P〈0.05）. The triglyceride concentration was considerably raised in the DM group compared with normal control group in all of the time points（P〈0. 01 ） ,however, the rise of triglyceride concentration was found only in 12 weeks in LBP group（P〈0.05）. The cholesterol level was increased in 8 and 12 weeks in DM group compared with normal control group and that of LBP group went up only in 12 weeks（ P〈0.01 ）. The Evans blue contents in dry retina tissue were（26.23±2.00） , （29.78± 1.78 ） and（ 34.08 ±3.03 ） μg/g in 4,8,12 weeks in the DM group, and those of LBP were （ 13.27 ±0. 77 ） , （ 18.01 ±1. 77 ） , （25.05 ± 1.50 ） μg/g, showing statistical differences between two groups （ P〈0. 01 ）. However, in comparison with normal control group （ 12. 34 ± 4. 30,12.76 ± 2.11,12.45 ± 4. 40μ/g ） , the Even blue content were elevated in various time points （P〈 0.01 ）. Conclusions LBP can suppress the increase of the blood-retinal barrier permeability in STZ-induced diabetic rat by lowing the levels of blood glucose, triglyceride and total cholesterol. These results suggest that LBP has a therapeutical effect on DR.