丝胶对2型糖尿病大鼠视网膜低氧诱导因子-1ɑ表达的作用
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摘要
目的探讨丝胶对2型糖尿病大鼠视网膜低氧诱导因子-1ɑ(HIF-1ɑ)表达的影响。方法将48只SPF级健康雄性SD大鼠依照随机数字分配方法随机分为正常对照组、糖尿病模型组、丝胶治疗组和导升明阳性对照组,每组12只。糖尿病模型组、丝胶治疗组、导升明阳性对照组大鼠均采用链脲佐菌素(STZ)连续腹腔注射3d并给予高脂饲料饮食法制备糖尿病大鼠模型;成模后分别用生理盐水、2.4g/(kg·d)丝胶溶液和0.2g/(kg·d)导升明溶液灌胃35d。苏木精-伊红染色观察各组大鼠视网膜组织的形态学变化;Western blot技术、实时荧光定量PCR技术检测各组大鼠视网膜组织HIF-1ɑ蛋白及mRNA的相对表达量。结果正常对照组大鼠视网膜组织结构正常,糖尿病模型组大鼠视网膜组织形态学出现明显的病理变化,HIF-1ɑ蛋白及mRNA相对表达量高于正常对照组(P<0.05)。导升明阳性对照组、丝胶治疗组大鼠视网膜组织形态学的病理变化减轻,HIF-1ɑ蛋白及mRNA相对表达量均低于糖尿病模型组(P<0.05)。结论丝胶可能通过下调视网膜HIF-1ɑ表达,从而对糖尿病视网膜微血管病变发挥保护作用。
Objective To investigate the effects of sericinon hypoxia inducible factor-1ɑ(HIF-1ɑ)expression in retina of type 2 diabetes mellitus rats.Methods Forty-eight specific pathogen free male SD rats were randomly divided into normal control group,diabetes model group,sericin-treated group and doxium positive control group and 12 rats for each group.The diabetic models were established by intraperitoneal injection of streptozotocin for 3consecutive days and feeding up with high lipid foods in the rats of the diabetes model group,sericin-treated group and doxium positive control group,and normal salinesolution,2.4g/(kg·d)sericin soulution and 0.2g/(kg·d)doxiumsoulution were used by gavage administration,respectively,for 35 days.Hematoxylin-eosinstaining was used to observe the morphological changes of the retina in each group.Western blot and realtime fluorescence quantitative PCR were respectively used to detect HIF-1ɑprotein and mRNA expressions in retina of each group.Results The retinal strcture was normal in the normal control group.The retinal morphology of diabetes model group changed obviously.The relative level expressions of protein and mRNA of HIF-1ɑin retina were significantly higher in diabetes model group,compared with normal control rats(P<0.05).The retinal morphology of the sericin treatment group and doxium positive control group changed less obviously than diabetes model group.The relative level expressions of protein and mRNA of HIF-1ɑin retina were significantly lower in sericin treatment group and doxium positive control group,compared with diabetes model group(P<0.05).Conclusions Sericin might protect the microangiopathy of diabetic retinopathy by down regulating HIF-1ɑexpression in retina.
Objective To investigate the effects of sericinon hypoxia inducible factor-1ɑ(HIF-1ɑ)expression in retina of type 2 diabetes mellitus rats.Methods Forty-eight specific pathogen free male SD rats were randomly divided into normal control group,diabetes model group,sericin-treated group and doxium positive control group and 12 rats for each group.The diabetic models were established by intraperitoneal injection of streptozotocin for 3consecutive days and feeding up with high lipid foods in the rats of the diabetes model group,sericin-treated group and doxium positive control group,and normal salinesolution,2.4g/(kg·d)sericin soulution and 0.2g/(kg·d)doxiumsoulution were used by gavage administration,respectively,for 35 days.Hematoxylin-eosinstaining was used to observe the morphological changes of the retina in each group.Western blot and realtime fluorescence quantitative PCR were respectively used to detect HIF-1ɑprotein and mRNA expressions in retina of each group.Results The retinal strcture was normal in the normal control group.The retinal morphology of diabetes model group changed obviously.The relative level expressions of protein and mRNA of HIF-1ɑin retina were significantly higher in diabetes model group,compared with normal control rats(P<0.05).The retinal morphology of the sericin treatment group and doxium positive control group changed less obviously than diabetes model group.The relative level expressions of protein and mRNA of HIF-1ɑin retina were significantly lower in sericin treatment group and doxium positive control group,compared with diabetes model group(P<0.05).Conclusions Sericin might protect the microangiopathy of diabetic retinopathy by down regulating HIF-1ɑexpression in retina.
引文
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[10]Huang H,He J,ohnson D,et al.Deletion of placental growth factor prevents diabetic retinopathy and is associated with Akt activation and HIF1α-VEGF pathway Inhibition[J].Diabetes,2015,64(1):200-212
[11]Cramer T,Yamanishi Y,Clausen BE,et al.HIF-1αis essential for myeloid cell-mediated inflammation[J].Cell,2003,112(5):645-657
[12]Zhang X,Liu W,Wu S,et al.Calcium dobesilate for diabetic retinopathy:a systematic review and metaanalysis[J].Sci China Life Sci,2015,58(1):101-107
[2]Wu Y,Tang L,Chen B.Oxidative stress:implications for the development of diabetic retinopathy and antioxidant therapeutic perspectives[J].Oxidative Medicine and Cellular Longevity,2014,2014:752387
[3]Kowluru RA,Kowluru A,Mishra M.Oxidative stress and epigenetic modifications in the pathogenesis of diabetic retinopathy[J].Prog Retin Eye Res,2015,48:40-61
[4]Aramwit P,Towiwat P,Srichana T.Anti-inflammatory potential of silk sericin[J].Nat Prod Commun,2013,8(4):501-504
[5]付秀美,钟美蓉,付文亮,等.丝胶对2型糖尿病大鼠血糖和血脂的影响[J].中国老年学杂志,2011,31(1):103-105
[6]郝祥俊,于晓敏,宋成军,等.丝胶对糖尿病大鼠肾脏ERK信号通路的影响[J].中国医科大学学报,2013,42(1):60-64
[7]Hagen T.Oxygen versus reactive oxygen in the regulation of HIF-1a:The Balance Tips[J].Biochemistry Research International,2012,2012:436981
[8]Hong-Tao Yan,Guan-Fang Su.Expression and significance of HIF-1ɑand VEGF in rats with diabetic retinopathy[J].Asian Pacific Journal of Tropical Medicine,2014,7(3):237-240
[9]Kietzmann T,Mennerich D,Dimova EY.Hypoxiainducible factors(HIFs)and phosphorylation:impact on stability,localization,and transactivity[J].Frontiers in Cell and Developmental Biology,2016,4:11
[10]Huang H,He J,ohnson D,et al.Deletion of placental growth factor prevents diabetic retinopathy and is associated with Akt activation and HIF1α-VEGF pathway Inhibition[J].Diabetes,2015,64(1):200-212
[11]Cramer T,Yamanishi Y,Clausen BE,et al.HIF-1αis essential for myeloid cell-mediated inflammation[J].Cell,2003,112(5):645-657
[12]Zhang X,Liu W,Wu S,et al.Calcium dobesilate for diabetic retinopathy:a systematic review and metaanalysis[J].Sci China Life Sci,2015,58(1):101-107