双丹明目胶囊对糖尿病大鼠模型视网膜VEGF-a、VEGF-b、VEGF-c及其受体Flk-1表达的影响（英文）
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摘要
目的观察双丹明目胶囊对糖尿病大鼠模型视网膜VEGF-a、VEGF-b、VEGF-c及其受体Flk-1表达的影响。方法将40只SD大鼠,采用随机数字法分为空白组(A)、模型组(B)、双丹明目组(C)、阳性对照组(D) 4组,每组10只20眼。将B、C、D三组实验大鼠采用STZ 50mg/kg的剂量一次性大鼠尾静脉注射法建立糖尿病视网膜病变大鼠模型,造模后1周开始连续灌胃用药,灌胃后8周,处死动物,采用免疫组化法检测视网膜组织中VEGF-a、VEGF-b、VEGF-c及其受体Flk-1的表达。结果成模后用药第8周,模型组、双丹明目组、阳性对照组视网膜中VEGF-a、VEGF-b、VEGF-c及其受体Flk-1蛋白表达平均灰度值均低于正常组,平均光密度均高于正常组,其中:模型组与正常组比较,差异均具有统计学意义(P<0.01);双丹明目组、阳性对照组VEGF-a、VEGF-b、VEGF-c及其受体Flk-1表达的平均灰度值均高于模型组、平均光密度值均低于模型组(P<0.05或P<0.01)。结论双丹明目胶囊能明显降低VEGF-a、VEGF-b、VEGF-c及其受体Flk-1在糖尿病模型大鼠视网膜中的表达,对其视网膜有一定的保护作用。
Objective The effects of Shuang Dan Ming Mu capsule on expression of VEGF-a, VEGF-b, VEGF-c and the VEGF receptor, Flk-1, were examined in a diabetic retinopathy rats model. Methods Forty Sprague-Dawley(SD) rats were randomized into Groups A(blank), B(model), C(Shuang Dan Ming Mu) and D(positive control) group, with each group containing 10 rats and 20 eyes. Rats from groups B, C and D were administered one dose of 50 mg/kg streptozotocin(STZ) by tail vein injection to establish a diabetic rat model. One week after model preparation, medication was continuously administered by gavage. After gavage for 8 weeks, the animals were sacrificed and retinal expression of VEGF-a, VEGF-b, VEGF-c and Flk-1 was quantified by immunohistochemical analysis. Results At week 8 of drug administration after model preparation, the average protein expression grayscale values for VEGF-a, VEGF-b, VEGF-c and Flk-1 in the rats model, Shuang Dan Ming Mu and positive control groups were all lower than those in the normal group, while the mean optical density values were higher than those in the normal group. When the model group was compared to the normal group, the difference was extremely significant(P < 0.01). The mean grayscale values of VEGF-a, VEGF-b, VEGF-c and Flk-1 in the Shuang Dan Ming Mu and positive control groups were all higher than those in the model group, while the mean optical density values were lower than those in the model group(P < 0.05 or 0.01). Conclusion Shuang Dan Ming Mu capsule can significantly decrease the expression of VEGF-a, VEGF-b, VEGF-c and Flk-1 in the retinas of diabetic model rats and exhibit some protective effects in their retinas.
Objective The effects of Shuang Dan Ming Mu capsule on expression of VEGF-a, VEGF-b, VEGF-c and the VEGF receptor, Flk-1, were examined in a diabetic retinopathy rats model. Methods Forty Sprague-Dawley(SD) rats were randomized into Groups A(blank), B(model), C(Shuang Dan Ming Mu) and D(positive control) group, with each group containing 10 rats and 20 eyes. Rats from groups B, C and D were administered one dose of 50 mg/kg streptozotocin(STZ) by tail vein injection to establish a diabetic rat model. One week after model preparation, medication was continuously administered by gavage. After gavage for 8 weeks, the animals were sacrificed and retinal expression of VEGF-a, VEGF-b, VEGF-c and Flk-1 was quantified by immunohistochemical analysis. Results At week 8 of drug administration after model preparation, the average protein expression grayscale values for VEGF-a, VEGF-b, VEGF-c and Flk-1 in the rats model, Shuang Dan Ming Mu and positive control groups were all lower than those in the normal group, while the mean optical density values were higher than those in the normal group. When the model group was compared to the normal group, the difference was extremely significant(P < 0.01). The mean grayscale values of VEGF-a, VEGF-b, VEGF-c and Flk-1 in the Shuang Dan Ming Mu and positive control groups were all higher than those in the model group, while the mean optical density values were lower than those in the model group(P < 0.05 or 0.01). Conclusion Shuang Dan Ming Mu capsule can significantly decrease the expression of VEGF-a, VEGF-b, VEGF-c and Flk-1 in the retinas of diabetic model rats and exhibit some protective effects in their retinas.
引文
[1]QIN Y H,LI W J,ZHANG X,et al.Effects of Shuangdanmingmu capsule on retinal vascular morphology and VEGF expression in rats with diabetic retinopathy.Int Eye Sci,2015,15(1):29-33.
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[3]QIN Y H,LI W J,ZHANG X,et al.Effects of Shuangdan Mingmu Capsule on the Expression of Retinal VEGF and VEGFR Protein Activity in Rats with Diabetic Retinopathy.Journal of Hunan University of Chinese Medicine,2015,35(6):1-3.
[4]NAGAOKA T,SATO E,TAKAHASHI A,et al.Impaired retinal circulation in patients with type 2diabetes mellitus:retinal laser doppler velocimetry study.Invest Ophthalmol Vis Sci,2010,51(12):6729.
[5]CHEN L J,MIAO L.Inhibitive effects of recombinant human endostatin on choroidal neovascularization.Rec Adv Ophthalmol,2012,32(10):922-925.
[6]PENG Q H.Ophthalmology of Chinese Medicine[M].Chinese Press of Traditional Chinese Medicine,2012:187.
[7]CHEN X D,PENG Q H,YAN J C,et al.Clinical observation of Fuming Table on diabetic retinopathy after retinal laser photocoagulation.Journal of Hunan University of Chinese Medicine,2016,36(1):63-65.
[8]TU L Y,WANG W C,WANG Y L.Efficacy and safety of Shuangdan Mingmu capsule in treating diabetic retinopathy.Chinese Journal of New Drugs,2009,18(24):2331-2336.
[9]PANG Y H.Clinical observation on treatment of diabetic retinopathy with Shuang Dan Ming Mu capsule.Diabetes New World,2015,(3):39.
[10]QIN Y H,LI F,TU L Y,et al.Multicentric clinical study of Shuangdan Mingmu capsule on diabetic retinopathy.Journal of Hunan University of Chinese Medicine,2010,30(1):46-51.
[11]LU C,SHI C H.Relationship between VEGFfamily/VEGF receptors and pathogenesis of diabetic retinopathy.Int Eye Sci,2007,7(5):1400-1402.
[12]NAGY J A,BENJAMIN L,ZENG H,et al.Vascular permeability,vascular hyperpermeability and angiogenesis.Angiogenesis,2008(11):109-119.
[13]ZHANG D M,QING C.Vascular Endothelial Growth Factor Family and Tumor Angiogenesis.Medical Recapitulate,2017,23(3):417-420.
[14]SALVEN P,LYMBOUSSAKI A,HEIKKILA P,et al.Vascular endothelial growth factors VEGF-B and VEGF-C are expressed in human tumors.Am J Pathol,1998,153(1):103-108.
[15]CAO Y,LINDEN P,FAMEBO J,et al.Vascular endothelial growth factor C induces angiogenesis in vivo.Proc Natl Acad Sci USA,1998,95(24):14389-14394.
[16]WITZENBICHLER B,ASAHARA T,MUROHARA T,et al.Vascular endothelial growth factor-C(VEGF-C/VEGF-2)promotes angiogenesis in the setting of tissue ischemia.Am J Pathol,1998,153(2):381-394.
[17]ANTONERTTI D A,KLEIN R,GARDNER T W.Diabetic retionpathy.N Engl J Med,2012,366(13):11227-11239.
[2]QIN Y H,LI W J,ZHANG X,et al.Effects of Shuangdanmingmu capsule on blood glucose and retinopathy in rats with diabetic retinopathy.Int Eye Sci,2014,14(11):1943-1945.
[3]QIN Y H,LI W J,ZHANG X,et al.Effects of Shuangdan Mingmu Capsule on the Expression of Retinal VEGF and VEGFR Protein Activity in Rats with Diabetic Retinopathy.Journal of Hunan University of Chinese Medicine,2015,35(6):1-3.
[4]NAGAOKA T,SATO E,TAKAHASHI A,et al.Impaired retinal circulation in patients with type 2diabetes mellitus:retinal laser doppler velocimetry study.Invest Ophthalmol Vis Sci,2010,51(12):6729.
[5]CHEN L J,MIAO L.Inhibitive effects of recombinant human endostatin on choroidal neovascularization.Rec Adv Ophthalmol,2012,32(10):922-925.
[6]PENG Q H.Ophthalmology of Chinese Medicine[M].Chinese Press of Traditional Chinese Medicine,2012:187.
[7]CHEN X D,PENG Q H,YAN J C,et al.Clinical observation of Fuming Table on diabetic retinopathy after retinal laser photocoagulation.Journal of Hunan University of Chinese Medicine,2016,36(1):63-65.
[8]TU L Y,WANG W C,WANG Y L.Efficacy and safety of Shuangdan Mingmu capsule in treating diabetic retinopathy.Chinese Journal of New Drugs,2009,18(24):2331-2336.
[9]PANG Y H.Clinical observation on treatment of diabetic retinopathy with Shuang Dan Ming Mu capsule.Diabetes New World,2015,(3):39.
[10]QIN Y H,LI F,TU L Y,et al.Multicentric clinical study of Shuangdan Mingmu capsule on diabetic retinopathy.Journal of Hunan University of Chinese Medicine,2010,30(1):46-51.
[11]LU C,SHI C H.Relationship between VEGFfamily/VEGF receptors and pathogenesis of diabetic retinopathy.Int Eye Sci,2007,7(5):1400-1402.
[12]NAGY J A,BENJAMIN L,ZENG H,et al.Vascular permeability,vascular hyperpermeability and angiogenesis.Angiogenesis,2008(11):109-119.
[13]ZHANG D M,QING C.Vascular Endothelial Growth Factor Family and Tumor Angiogenesis.Medical Recapitulate,2017,23(3):417-420.
[14]SALVEN P,LYMBOUSSAKI A,HEIKKILA P,et al.Vascular endothelial growth factors VEGF-B and VEGF-C are expressed in human tumors.Am J Pathol,1998,153(1):103-108.
[15]CAO Y,LINDEN P,FAMEBO J,et al.Vascular endothelial growth factor C induces angiogenesis in vivo.Proc Natl Acad Sci USA,1998,95(24):14389-14394.
[16]WITZENBICHLER B,ASAHARA T,MUROHARA T,et al.Vascular endothelial growth factor-C(VEGF-C/VEGF-2)promotes angiogenesis in the setting of tissue ischemia.Am J Pathol,1998,153(2):381-394.
[17]ANTONERTTI D A,KLEIN R,GARDNER T W.Diabetic retionpathy.N Engl J Med,2012,366(13):11227-11239.