黄连总生物碱与三七总皂苷组合物对2型糖尿病视网膜病变的保护作用  

Protective Effect of Total Alkaloids of Coptis chinensis Combined with Total Saponins of Panax notoginseng on Type 2 Diabetic Retinopathy

作　　者：周赫 王晓 刘博[2] 王鑫[2] 张译心 林玥 纪凤兰[2] 温富春[2] 丁涛[2] 徐惠波[2] Zhou He;Wang Xiao;Liu Bo;Wang Xin;Zhang Yixin;Lin Yue;Ji Fenglan;Wen Fuchun;Ding Tao;Xu Huibo(Changchun University of Traditional Chinese Medicine,Changchun 130117;Jilin Academy of Traditional Chinese Medicine,Changchun 130012)

机构地区：[1]长春中医药大学,长春130117 [2]吉林省中医药科学院,长春130012

出　　处：《中药药理与临床》2020年第6期144-150,共7页Pharmacology and Clinics of Chinese Materia Medica

基　　金：国家重大新药创制专项(编号:2017ZX09301031);吉林省科技发展计划项目(编号:20170311012YY)。

摘　　要：目的:观察黄连总生物碱与三七总皂苷组合物(HS)对高糖高脂结合链脲佐菌素(STZ)诱导的小鼠2型糖尿病视网膜病变(diabetic retinopathy,DR)的影响。方法:雄性Balb/C小鼠高糖高脂喂养2 w后,腹腔注射STZ 100 mg/kg,稳定2 w后测空腹血糖,并且将空腹血糖水平达8.7 mmol/L以上的小鼠进行分组,继续饲养4 w;空白对照组和模型对照组随机取少量动物视网膜进行HE染色观察,模型对照组动物出现视网膜病变趋势后,二甲双胍220 mg/kg组和黄连总生物碱与三七总皂苷组合物685 mg/kg组动物开始灌胃给药,每天1次,连续给药8 w。测量小鼠给药后血糖,检测糖耐量(AUC)、总胆固醇(TC)、高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL-C)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α),免疫组化法检测小鼠视网膜组织胶质纤维酸性蛋白(GFAP)的表达,HE染色观察动物胰腺病理变化,并检测视网膜厚度和视网膜神经节细胞(RGCs)数。结果:与空白对照组相比,小鼠造模后血糖、血脂、炎症因子(IL-6和TNF-α)和GFAP水平均显著升高,胰岛及视网膜组织损伤较重,小鼠视网膜厚度明显变薄,RGCs数量明显下降(P<0.05)。与模型对照组相比,黄连总生物碱与三七总皂苷组合物685 mg/kg组给药后小鼠血糖明显降低(P<0.05),葡萄糖灌胃后0 min^120 min AUC明显降低(P<0.01);给药后小鼠血清中TC、LDL-C含量降低,HDL-C水平升高;血清中IL-6及TNF-α水平均显著降低(P<0.01);视网膜中GFAP的表达量明显减少(P<0.05),效果略优于二甲双胍220 mg/kg组;HE染色结果显示:黄连总生物碱与三七总皂苷685 mg/kg组合物组小鼠胰腺内可见体积较大,数量较多的胰岛组织散在分布,胰岛数量高于模型对照组;视网膜神经节细胞层内的RGCs数量明显增多(P<0.05)。结论:黄连总生物碱与三七总皂苷组合物对2型糖尿病视网膜病变小鼠的保护作用可能与改善糖脂代谢异常、降低相关炎症因子水平和�Objective:To observe the effect of the combination of total alkaloids of Coptis and total saponins of Panax notoginseng(HS)on type 2 diabetic retinopathy(DR)induced by high-sugar and high-fat combined with streptozotocin(STZ)in mice.Methods:Male Balb/C mice were fed with high sugar and high fat for 2 weeks,STZ(100 mg/kg)was intraperitoneally injected,the fasting blood glucose was measured after stabilized for 2 weeks.Mice with fasting blood glucose level higher than 8.7 mmol/L were divided into groups and were administered for 4 weeks.Then a small part of animal retinas were randomly taken in the control group and the model group for HE staining.After the retinopathy began to appeare in the model group,animals in metformin(220 mg/kg)group and HS(685 mg/kg)group were orally administered once a day for 8 weeks.After administration,the blood glucose,the glucose tolerance(AUC),the total cholesterol(TC),the high density lipoprotein(HDL-C),the low density lipoprotein(LDL-C),the levels of interleukin-6(IL-6))and tumor necrosis factor-α(TNF-α)were determined.Immunohistochemical method was used to detect the expression of glial fibrillary acidic protein(GFAP)in the mouse retina,HE staining was used to observe the pathological changes of animal pancreas,also the retinal thickness and the number of retinal ganglion cells(RGCs)were measured.Results:Compared with the control group,the levels of blood glucose,blood lipids,inflammatory factors(IL-6 and TNF-α)and GFAP were significantly increased after modeling,the pancreatic islets and retinal tissues were severely damaged,and the thicknesses of mice retinas were obviously decreased,the number of RGCs was significantly decreased(P<0.05).Compared with the model group,the blood sugar of mice in HS(685 mg/kg)group was significantly reduced(P<0.05),and the AUC was significantly decreased(P<0.001)in 0-120 min after glucose administration.After treatment,the levels of TC and LDL-C in the serum of mice were decreased,and the level of HDL-C was increased,the levels of IL-6 and TNF-�

关 键 词：黄连总生物碱 三七总皂苷 2型糖尿病 糖尿病视网膜病变 炎性因子 

分 类 号：R285.5[医药卫生—中药学]