双丹明目胶囊对糖尿病视网膜病变兔视网膜的保护作用及机制
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摘要
目的:探讨双丹明目胶囊对糖尿病视网膜病变(DR)兔视网膜的保护作用,并阐明其可能的保护机制。方法:采用重复性静脉注射四氧嘧啶(200mg/kg)建立DR兔模型,并随机分为模型组,双丹明目胶囊高、中、低剂量组(2.88、1.44、0.72g/kg),阳性药组(羟苯磺酸钙,5.8mg/kg),以正常兔为正常组。连续给药30d后,取兔血浆做血液分析,HE染色观察视网膜损伤情况,ELISA试剂盒检测视网膜中超氧化物歧化酶(SOD)、丙二醛(MDA)、血栓素B_2(TXB_2)、6-酮-前列腺素F_(1α)(6-Keto-PGF_(1α))含量。结果:高剂量组和阳性药组DR模型兔的视网膜损伤情况均显著减轻。高剂量组血糖值显著降低(P<0.05)、血小板黏附率与优球蛋白溶解时间均显著减少(P<0.05),阳性药组和高剂量组红细胞滤过率显著升高(P<0.05);同时,药物干预后,高剂量组SOD、6-Keto-PGF_(1α)含量显著上升(P<0.01,P<0.05),MDA、TXB_2含量显著下降(P<0.01,P<0.05),中剂量组SOD含量显著上升(P<0.05)。结论:双丹明目胶囊能明显减轻DR模型兔视网膜的病变程度,其作用可能与恢复TXB_2/6-keto-PGF_(1α)平衡及抑制氧化应激损伤有关。
Objective: To explore the protective effect of Shuangdan Mingmu Capsule on the rabbit retina of diabetic retinopathy(DR) and to clarify its possible protective mechanism. Methods: DR rabbit models were established by repetitive intravenous injection of alloxan(200 mg/kg) and randomly divided into model group, high, medium and low dose of Shuangdan Mingmu Capsule groups(2.88, 1.44, 0.72 g/kg), positive drug group(Calcium Dobesilate, 5.8 mg/kg), while normal rabbits as control group. After thirty days of the continuous administration, the blood samples of the rabbits were taken for blood analysis and HE staining was used to observe the retinal damage, the ELISA kit was used to detect the contents of superoxide dismutase(SOD),malondialdehyde(MDA), thromboxane B_2(TXB_2), 6-Keto-prostaglandin F_(1α)(6-Keto-PGF_(1α)) in the retina. Results: The retinal damage of DR model rabbits in high dose group and positive drug group was significantly alleviated. In high dose group, the blood sugar value was significantly decreased in high dose group(P<0.05), and both platelet adhesion rate and euglobulin dissolution time were significantly reduced(P<0.05). In high dose group and positive drug group, the Erythrocyte Filtration Rate was significantly increased(P<0.05). At the same time, after drug intervention, the content of MDA and TXB_2 in the high dose group significantly decreased(P<0.01, P<0.05), while the content of SOD and 6-Keto-PGF_(1α) increased significantly(P<0.01, P<0.05),and the content of SOD in the middle dose group increased significantly as well(P<0.05). Conclusion: Shuangdan Mingmu Capsule could significantly reduce the damage degree of retinopathy in DR model rabbits, which may be related to the restoration of TXB_2/6-keto-PGF_(1α) balance and the inhibition of oxidative stress injury.
Objective: To explore the protective effect of Shuangdan Mingmu Capsule on the rabbit retina of diabetic retinopathy(DR) and to clarify its possible protective mechanism. Methods: DR rabbit models were established by repetitive intravenous injection of alloxan(200 mg/kg) and randomly divided into model group, high, medium and low dose of Shuangdan Mingmu Capsule groups(2.88, 1.44, 0.72 g/kg), positive drug group(Calcium Dobesilate, 5.8 mg/kg), while normal rabbits as control group. After thirty days of the continuous administration, the blood samples of the rabbits were taken for blood analysis and HE staining was used to observe the retinal damage, the ELISA kit was used to detect the contents of superoxide dismutase(SOD),malondialdehyde(MDA), thromboxane B_2(TXB_2), 6-Keto-prostaglandin F_(1α)(6-Keto-PGF_(1α)) in the retina. Results: The retinal damage of DR model rabbits in high dose group and positive drug group was significantly alleviated. In high dose group, the blood sugar value was significantly decreased in high dose group(P<0.05), and both platelet adhesion rate and euglobulin dissolution time were significantly reduced(P<0.05). In high dose group and positive drug group, the Erythrocyte Filtration Rate was significantly increased(P<0.05). At the same time, after drug intervention, the content of MDA and TXB_2 in the high dose group significantly decreased(P<0.01, P<0.05), while the content of SOD and 6-Keto-PGF_(1α) increased significantly(P<0.01, P<0.05),and the content of SOD in the middle dose group increased significantly as well(P<0.05). Conclusion: Shuangdan Mingmu Capsule could significantly reduce the damage degree of retinopathy in DR model rabbits, which may be related to the restoration of TXB_2/6-keto-PGF_(1α) balance and the inhibition of oxidative stress injury.
引文
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[8]田文杨,白颖,丛佳林.基于文献的糖尿病视网膜病变中药用药规律研究.中华中医药杂志,2017,32(6):2779-2782
[9]Tagami M,Kusuhara S,Imai H,et al.MRP4 knockdown enhances migration,suppresses apoptosis,and produces aggregated morphology in human retinal vascular endothelial cells.Biochem Biophys Res Commun,2010,400(4):593-598
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[11]万嘉洋,万海同,何昱,等.活血康脑颗粒对大鼠脑缺血再灌注损伤的保护作用.中成药,2017,39(11):2236-2242
[12]张艳,胡樱凡,杨巧巧,等.芪灯明目胶囊及有效组分对糖尿病视网膜病变大鼠的影响及机制研究.中药药理与临床,2015,31(4):166-170
[13]Kundu D,Mandal T,Nandi M,et al.Oxidative stress in diabetic patients with retinopathy.Ann Afr Med,2014,13(1):41-44
[2]Dow C,Mancini F,Rajaobelina K,et al.Diet and risk of diabetic retinopathy:A systematic review.Eur J Epidemiol,2017,12(4):1124-1129
[3]Huang O S,Tay W T,Ong P G,et al.Prevalence and determinants of undiagnosed diabetic retinopathy and vision-threatening retinopathy in a multiethnic Asian cohort:The Singapore Epidemiology of Eye Diseases study.Br J Ophthalmol,2015,99(12):1614-1621
[4]Magri C J,Fava S.Red blood cell distribution width and diabetesassociated complications.Diabetes Metab Syndr,2014,8(1):13-17
[5]刘淑蕊,梁慧超,王颖芳,等.姜炭对虚寒性出血大鼠凝血时间、血液粘度、优球蛋白溶解时间的影响.时珍国医国药,2015,26(5):1041-1042
[6]秦裕辉,李文娟,张熙,等.双丹明目胶囊对糖尿病视网膜病变大鼠视网膜VEGF和VEGFR蛋白表达的影响.湖南中医药大学学报,2015,35(6):1-3
[7]符超君,凌艳君,颜家朝,等.双丹明目胶囊对糖尿病视网膜病变大鼠视网膜组织低氧诱导因子-1α和核因子-κB表达的影响.中国中医药信息杂志,2018,25(6):44-47
[8]田文杨,白颖,丛佳林.基于文献的糖尿病视网膜病变中药用药规律研究.中华中医药杂志,2017,32(6):2779-2782
[9]Tagami M,Kusuhara S,Imai H,et al.MRP4 knockdown enhances migration,suppresses apoptosis,and produces aggregated morphology in human retinal vascular endothelial cells.Biochem Biophys Res Commun,2010,400(4):593-598
[10]Wang G X,Liang C J,Yao J Y.Effect of a novel fibrinolytic enzyme FA-I on thrombosis and thrombolysis.Journal of Sichuan University(Medical Science Edition),2009,40(2):288-291
[11]万嘉洋,万海同,何昱,等.活血康脑颗粒对大鼠脑缺血再灌注损伤的保护作用.中成药,2017,39(11):2236-2242
[12]张艳,胡樱凡,杨巧巧,等.芪灯明目胶囊及有效组分对糖尿病视网膜病变大鼠的影响及机制研究.中药药理与临床,2015,31(4):166-170
[13]Kundu D,Mandal T,Nandi M,et al.Oxidative stress in diabetic patients with retinopathy.Ann Afr Med,2014,13(1):41-44