枸杞多糖对糖尿病大鼠视网膜神经元的保护作用及其机制
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摘要
目的:观察枸杞多糖(LBP)对糖尿病大鼠视网膜神经细胞的保护作用,并探讨其作用机制。方法:18只SD大鼠随机分为3组(n=6):正常对照组(NC),糖尿病模型组(DM)和LBP治疗组(DM+LBP),通过一次性腹腔注射链脲佐菌素(STZ)的方法制备糖尿病大鼠模型。DM+LBP组按1 mg/(kg·d)剂量的LBP灌胃12周。治疗结束后检测大鼠体重、空腹血糖、视网膜活性氧簇(ROS)的生成、视网膜神经节细胞(RGCs)和无长突细胞的表达、视网膜NF-E2相关因子2(Nrf2)和血红素加氧酶-1(HO-1)的蛋白表达。结果:STZ诱导糖尿病大鼠模型造模成功率100%。与NC组相比,DM组大鼠体重明显降低、空腹血糖值升高、ROS的生成明显增加、RGCs和无长突细胞的数量均明显减少(P<0.01)。与DM组相比,LBP治疗组大鼠体重升高、血糖降低、ROS的生成减少、RGCs和无长突细胞的数量均明显增加(P<0.01或P<0.05);视网膜Nrf2和HO-1的蛋白表达均明显升高(P<0.01)。结论:LBP能改善糖尿病大鼠视网膜的氧化应激状态,对糖尿病大鼠视网膜神经细胞有一定的保护效应,其作用机制可能与其激活Nrf2/HO-1信号通路有关。
Objective: To clarify whether lycium barbarum polysaccharides( LBP) have protective effects on retina neuronal cells in diabetic rats and to identify the related mechanism involved in this process. Methods: Eighteen SD rats were randomly divided into 3 groups( n = 6) : normal control group( NC),diabetes mellitus group( DM) and LBP-treatment group( DM+LBP). The diabetic rat model was induced by single intraperitoneal injection of streptozotocin( STZ). The rats in DM+LBP group were treated with LBP at the dose of 1 mg/kg by gavage,once a day for 12 weeks. After the treatment,the weight and blood glucose,the generation of reactive oxygen species( ROS),the surviving retinal ganglion cells( RGCs) and amacrine cells and the protein expressions of nuclear factor E2-related factor 2( Nrf2) and the heme oxygenase-1( HO-1) were detected. Results: The successful rate of diabetic model was100%. Compared with NC group,the rats of DM group caused weight loss,elevated blood glucose,a marked increase of ROS generation and a significant decrease in the number of RGCs and amacrine cells( P<0.01),and these effects were diminished or abolished by LBP treatment. Meanwhile,LBP significantly increased the expressions of Nrf2 and HO-1 in the retinas of diabetic rats( P < 0.01).Conclusion: LBP can improve retinal oxidative stress and exert beneficial neuroprotective effects in diabetic rats,and its mechanism may be associated with the activation of the Nrf2/HO-1 antioxidant pathway.
Objective: To clarify whether lycium barbarum polysaccharides( LBP) have protective effects on retina neuronal cells in diabetic rats and to identify the related mechanism involved in this process. Methods: Eighteen SD rats were randomly divided into 3 groups( n = 6) : normal control group( NC),diabetes mellitus group( DM) and LBP-treatment group( DM+LBP). The diabetic rat model was induced by single intraperitoneal injection of streptozotocin( STZ). The rats in DM+LBP group were treated with LBP at the dose of 1 mg/kg by gavage,once a day for 12 weeks. After the treatment,the weight and blood glucose,the generation of reactive oxygen species( ROS),the surviving retinal ganglion cells( RGCs) and amacrine cells and the protein expressions of nuclear factor E2-related factor 2( Nrf2) and the heme oxygenase-1( HO-1) were detected. Results: The successful rate of diabetic model was100%. Compared with NC group,the rats of DM group caused weight loss,elevated blood glucose,a marked increase of ROS generation and a significant decrease in the number of RGCs and amacrine cells( P<0.01),and these effects were diminished or abolished by LBP treatment. Meanwhile,LBP significantly increased the expressions of Nrf2 and HO-1 in the retinas of diabetic rats( P < 0.01).Conclusion: LBP can improve retinal oxidative stress and exert beneficial neuroprotective effects in diabetic rats,and its mechanism may be associated with the activation of the Nrf2/HO-1 antioxidant pathway.
引文
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[7]Li XM,Ma YL,Liu XJ.Effect of the Lycium barbarum polysaccharides on age-related oxidative stress in aged mice[J].J Ethnopharmacol,2007,111(3):504-511.
[8]Li XM.Protective effect of Lycium barbarum polysaccharides on streptozotocin-induced oxidative stress in rats[J].Int J Biol Macromol,2007,40(5):461-465.
[9]Shan X,Zhou J,Ma T,et al.Lycium barbarum polysaccharides reduce exercise-induced oxidative stress[J].Int J Mol Sci,2011,12(2):1081-1088.
[10]许拓,凌宏艳,龙佳,等.枸杞多糖对Hep G2细胞胰岛素抵抗的改善作用及机制研究[J].中国应用生理学杂志,2017,33(6):568-571.
[11]Brownlee M.The pathobiology of diabetic complications:a unifying mechanism[J].Diabetes,2005,54(6):1615-1625.
[12]宋丽君.南瓜多糖对糖尿病大鼠血糖、血脂及氧化应激能力的影响[J].中国应用生理学杂志,2015,31(1):65-66.
[13]潘虹,蒋淑君,刘红霞,等.莱菔硫烷对糖尿病大鼠视网膜神经细胞的保护作用[J].中国病理生理杂志,2017,33(11):1938-1944.
[14]Masuda T,Shimazawa M,Hara H.Retinal diseases associated with oxidative stress and the effects of a free radical scavenger(edaravone)[J].Oxid Med Cell Longev,2017,2017:9208489.
[15]Nabavi SF,Barber AJ,Spagnuolo C,et al.Nrf2 as molecular target for polyphenols:A novel therapeutic strategy in diabetic retinopathy[J].Crit Rev Clin Lab Sci,2016,53(5):293-312.
[16]Fan J,Xu G,Jiang T,et al.Pharmacologic induction of heme oxygenase-1 plays a protective role in diabetic retinopathy in rats[J].Invest Ophthalmol Vis Sci,2012,53(10):6541-6556.
[2]Neelam K,Goenadi CJ,Lun K,et al.Putative protective role of lutein and zeaxanthin in diabetic retinopathy[J].Br J Ophthalmol,2017,101(5):551-558.
[3]Li J,Wang JJ,Yu Q,et al.Inhibition of reactive oxygen species by Lovastatin downregulates vascular endothelial growth factor expression and ameliorates blood-retinal barrier breakdown in db/db mice:role of NADPH oxidase 4[J].Diabetes,2010,59(6):1528-1538.
[4]Liu Q,Zhang F,Zhang X,et al.Fenofibrate ameliorates diabetic retinopathy by modulating Nrf2 signaling and NL-RP3 inflammasome activation[J].Mol Cell Biochem,2018,445(1-2):105-115.
[5]He M,Pan H,Chang RC,et al.Activation of the Nrf2/HO-1 antioxidant pathway contributes to the protective effects of Lycium barbarum polysaccharides in the rodent retina after ischemia-reperfusion-induced damage[J].PLo S One,2014,9(1):e84800.
[6]马雅玲,陈凤,李小璐.枸杞多糖对糖尿病大鼠视网膜保护作用的研究[J].宁夏医科大学学报,2013,35(8):837-840.
[7]Li XM,Ma YL,Liu XJ.Effect of the Lycium barbarum polysaccharides on age-related oxidative stress in aged mice[J].J Ethnopharmacol,2007,111(3):504-511.
[8]Li XM.Protective effect of Lycium barbarum polysaccharides on streptozotocin-induced oxidative stress in rats[J].Int J Biol Macromol,2007,40(5):461-465.
[9]Shan X,Zhou J,Ma T,et al.Lycium barbarum polysaccharides reduce exercise-induced oxidative stress[J].Int J Mol Sci,2011,12(2):1081-1088.
[10]许拓,凌宏艳,龙佳,等.枸杞多糖对Hep G2细胞胰岛素抵抗的改善作用及机制研究[J].中国应用生理学杂志,2017,33(6):568-571.
[11]Brownlee M.The pathobiology of diabetic complications:a unifying mechanism[J].Diabetes,2005,54(6):1615-1625.
[12]宋丽君.南瓜多糖对糖尿病大鼠血糖、血脂及氧化应激能力的影响[J].中国应用生理学杂志,2015,31(1):65-66.
[13]潘虹,蒋淑君,刘红霞,等.莱菔硫烷对糖尿病大鼠视网膜神经细胞的保护作用[J].中国病理生理杂志,2017,33(11):1938-1944.
[14]Masuda T,Shimazawa M,Hara H.Retinal diseases associated with oxidative stress and the effects of a free radical scavenger(edaravone)[J].Oxid Med Cell Longev,2017,2017:9208489.
[15]Nabavi SF,Barber AJ,Spagnuolo C,et al.Nrf2 as molecular target for polyphenols:A novel therapeutic strategy in diabetic retinopathy[J].Crit Rev Clin Lab Sci,2016,53(5):293-312.
[16]Fan J,Xu G,Jiang T,et al.Pharmacologic induction of heme oxygenase-1 plays a protective role in diabetic retinopathy in rats[J].Invest Ophthalmol Vis Sci,2012,53(10):6541-6556.