PSP对STZ诱导的糖尿病大鼠眼保护作用的临床动态观察

Observation on the protective effect of polygonatum polysaccharide for eyes in streptozotocin induced diabetic rats

目的:应用不同剂量黄精多糖(polygona-polysaccharose,PSP)灌胃由链脲佐菌素(streptozotocin,STZ)诱导的糖尿病大鼠模型,在不同时间点对大鼠行前节检查、F-VEP、ERG、眼底荧光血管造影检查(FFA)观察眼部病变过程,眼内眦静脉采血葡萄糖氧化酶法(强生血糖仪)测空腹血糖值。探讨PSP对DM大鼠眼部病变的保护作用机制与治疗效果,为黄精多糖治疗糖尿病眼部病变提供实验依据及理论基础。方法:雄性SD大鼠100只随机被分为两组:糖尿病模型组80只(由STZ诱导造模)和空白对照组20只。再将糖尿病模型组随机分为4组,其中DM组(糖尿病对照组)20只,正常饲养,每日灌胃2m L生理盐水。PSP灌胃组三组,每组各20只,包括L组(低剂量PSP灌胃组,200mg/kg)、M组(中剂量PSP灌胃组,400mg/kg)、H组(高剂量PSP灌胃组,800mg/kg),每次灌胃剂量2m L;BC组(空白对照组)20只,灌胃等剂量生理盐水作为对照。造模成功后5组在相同条件下饲养,每天灌胃,并在第2、4、6、8、10、12wk行前节照相、眼底荧光血管造影检查(FFA),4、8、12wk行F-VEP、ERG检查。眼内眦静脉采血葡萄糖氧化酶法(强生血糖仪)测空腹血糖值。结果:DM、L、M、H组与BC组相比:空腹血糖水平明显增高(P<0.05)。L、M、H组与DM组相比:空腹血糖水平增高(P<0.05)。L、M、H三组之间呈时间与剂量依赖关系。眼前节检查可观察到有6只DM组、3只L组、1只M组大鼠出现了不同程度的白内障症状,并随着时间推移愈发加重,而BC组眼前节照相并未发现异常。DM组大鼠在F-VEP检查表现为P100峰潜时延长,PSP灌胃组与DM组相比P100峰潜时延长时间缩短,BC组无明显改变。在ERG中表现为DM组大鼠Max-R a和b波振幅下降51.2%和59.8%,Cone-R a和b波振幅下降31.4%和41.2%,Ops-OS值、30Hz Flicker N1-P1振幅下降,与BC组比较有显著统计学差异,PSP灌胃组情况好于DM组。在FFA检查中可发现DM组眼底与BC组相比出现背景荧光增强、大血管扭曲和毛细血管扩张、视网膜血管荧光素渗漏、视网膜内出血等典型糖尿病视网膜病变的表现,PSP灌胃组情况好于DM组。结论:PSP既能有效降低糖尿病大鼠的血糖水平,又能延缓糖尿病大鼠眼部并发症的进程,减缓白内障和糖尿病视网膜病变的发生发展,可以对眼部病变起到明显的治疗作用。其机制有可能为通过抑制糖基化终产物,改善糖脂质代谢,提高糖耐量,而对糖尿病晶状体代谢和视网膜微小血管病变发挥保护作用。

AIM：To apply different doses of polygona-polysaccharose（PSP） to diabetic rats model by gastrogavage that were induced by streptozotocin（STZ）,then check the rats about anterior segment,FVEP,ERG,fundus fluorescein angiography（FFA） and measure fasting blood glucose（glucose oxidase method） by inner canthus vein blood to observe the eye disease process at different time points and to discuss the protective effect of PSP on ocular lesions in DM rats and the treatment effect,to provide the experimental basis and theoretical basis for PSP treating diabetic ocular disease.·METHODS：One hundred male SD rats were randomly divided into 2 groups：diabetic model group（80 rats induced by STZ） and blank control group（20 rats）.Then the diabetic model group was randomly divided into 4 subgroups.The group DM（diabetic group） had 20 rats with normal diet and 2mL physiological saline for daily gavage.PSP gavaged groups included three subgroups and with 20 rats in each group,group L（low dose of PSP gavage group,200mg/kg）,group M（medium dose of PSP gavage group,400mg/kg）,group H（high dose of PSP gavage group,800mg/kg）.Every group was gavaged with 2mL PSP.Twenty rats in group BC（blank control group）,and they were gavaged saline of equal dose as control.After the success of modeling,5 groups were under the same conditions of feeding,and gavaged every day.At 2,4,6,8,10 and 12 wk,anterior segment examination and FFA were given.At 4,8 and12 wk,F-VEP and ERG were given.Fasting blood glucose（by glucose oxidase method） was measured through inner canthus vein blood.·RESULTS：Compared to BC group,fasting blood glucose levels were significantly higher in group DM,L,M and H（P0.05）.Compared to DM group,fasting blood glucose level decreased in L,M,H group（P0.05）.The fasting blood glucose levels of L,M and H groups showed a time and dose dependent relationship.After anterior segment examination,there were 6 rates in DM group,3 in L group,1 in M group with different degrees of cataract symptoms which became more serious with time.The BC group was not found any abnormal in the anterior segment.Examined by F-VEP,the rats in group DM showed extension of the P100 peak latency.Compared to the group DM,PSP gavaged group showed a shortened of the extension of the P100 peak latency,while the group BC had no obvious change.In the ERG examination,the rats in group DM showed that amplitude of Max-R a,b wave decreased by 51.2%,59.8%and amplitude of Cone-Ra,b wave decreased by31.4%,41.2%.The Ops OS value and amplitude of 30 Hz Picker N1- P1 decreased,there was a significant difference compared to group BC.PSP gavaged group was better than group DM.In the FFA examination,in group DM,we could find the typical manifestations of diabetic retinopathy background fluorescence enhancement,distortion of the blood vessels and blood capillary dilate,retinal vascular leakage of fluorescein and intraretinal hemmorhages compared with the group BC.PSP gavaged group was better than group DM.·CONCLUSION：PSP can effectively reduce the blood glucose levels of diabetic rats,and also can delay the process of ocular complications in diabetic rats,which have an obvious therapeutic effect on ocular lesions.The mechanism is likely to improve the metabolism of glucose and lipid metabolism,increase the amount of glucose tolerance,and play a protective role in diabetic lens metabolism and retinal microvascular disease.