聂辅娇, 刘志敏, 孙淑铭, 杨毅敬, 陈向东, 彭清华. 丹黄明目汤通过下调VEGF、上调PEDF表达抑制BN大鼠糖尿病视网膜病变激光术后的疾病进展[J]. Digital Chinese Medicine, 2019, 2(1): 19-28. DOI: 10.1016/j.dcmed.2019.05.003
引用本文: 聂辅娇, 刘志敏, 孙淑铭, 杨毅敬, 陈向东, 彭清华. 丹黄明目汤通过下调VEGF、上调PEDF表达抑制BN大鼠糖尿病视网膜病变激光术后的疾病进展[J]. Digital Chinese Medicine, 2019, 2(1): 19-28. DOI: 10.1016/j.dcmed.2019.05.003
NIE Fu-Jiao, LIU Zhi-Min, SUN Shu-Ming, YANG Yi-Jing, CHEN Xiang-Dong, PENG Qing-Hua. Dan Huang Ming Mu Recipe Suppresses the Progression of Streptozotocin-induced Diabetic Retinopathy After Retinal Laser Photocoagulation in Brown Norway Rats via Down-regulating Vascular Endothelial Growth Factor and Up-regulating Pigment Epithelium-derived Factor[J]. Digital Chinese Medicine, 2019, 2(1): 19-28. DOI: 10.1016/j.dcmed.2019.05.003
Citation: NIE Fu-Jiao, LIU Zhi-Min, SUN Shu-Ming, YANG Yi-Jing, CHEN Xiang-Dong, PENG Qing-Hua. Dan Huang Ming Mu Recipe Suppresses the Progression of Streptozotocin-induced Diabetic Retinopathy After Retinal Laser Photocoagulation in Brown Norway Rats via Down-regulating Vascular Endothelial Growth Factor and Up-regulating Pigment Epithelium-derived Factor[J]. Digital Chinese Medicine, 2019, 2(1): 19-28. DOI: 10.1016/j.dcmed.2019.05.003

丹黄明目汤通过下调VEGF、上调PEDF表达抑制BN大鼠糖尿病视网膜病变激光术后的疾病进展

Dan Huang Ming Mu Recipe Suppresses the Progression of Streptozotocin-induced Diabetic Retinopathy After Retinal Laser Photocoagulation in Brown Norway Rats via Down-regulating Vascular Endothelial Growth Factor and Up-regulating Pigment Epithelium-derived Factor

  • 摘要:
    目的探究养阴清热、活血利水之丹黄明目汤对糖尿病视网膜病变激光术后VEGF/PEDF调节机制的研究。
    方法将40只雄性棕色挪威(Brown Norway, BN)大鼠随机分为空白组(A组,10只)和模型组(30只)。采用40 mg/kg STZ腹腔注射诱导模型组大鼠建立DR模型,监测大鼠的体重和血糖,12周后进行FFA检查及血清P-Selectin、cAMP、cGMP的测定,经HE染色后光镜下观察视网膜组织形态,确认成功建立DR模型。所有模型组大鼠右眼行视网膜氩激光光凝,左眼不行激光光凝。将模型组随机分为B组(模型对照组)、C组(阳性对照组)、D组(丹黄明目汤组),每组10只大鼠。A组和B组予蒸馏水灌胃,C组予羟苯磺酸钙悬浮液灌胃,D组予丹黄明目汤灌胃。灌胃4周后,进行FFA检查,然后处死大鼠检测血清中P-Selectin、cAMP、cGMP的含量,以及视网膜组织中VEGF/PEDF的相对表达量。
    结果造模12周后,模型组大鼠血糖与空白组比较明显升高(P < 0.01);FFA检查可见模型组大鼠眼底有微血管瘤改变,空白组未见微血管瘤等眼底改变;HE染色可见模型组大鼠视网膜结构较空白组紊乱。灌胃4周后,丹黄明目汤组大鼠血清P-Selectin、cAMP、cGMP水平较模型对照组明显降低(P < 0.01)。组织病理学检查显示模型对照组大鼠视网膜水肿、眼底微血管破坏和视网膜破坏明显,丹黄明目汤组大鼠较模型对照组轻。与模型对照组相比,丹黄明目汤组和空白组大鼠的VEGF蛋白相对表达量低于模型对照组(P < 0.01),而丹黄明目汤组和空白组大鼠的PEDF蛋白相对表达量高于模型对照组(P < 0.01)。
    结论丹黄明目汤通过降低VEGF的相对表达量,并上调PEDF的相对表达量来修复DR激光光凝术后视网膜组织损伤。

     

    Abstract:
    ObjectiveTo analyze the effects of Dan Huang Ming Mu Recipe (DHMMR) (a pharmaceutical preparation from herbs and having the function of replenishing vital essence, removing heat, promoting blood circulation and excreting pathogenic water) on diabetic retinopathy (DR) after retinal laser photocoagulation through regulating the expression of vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF).
    MethodsForty male Brown Norway (BN) rats were randomly divided into blank group (group A, 10 BN rats) and model group (30 BN rats). DR models were induced by 40 mg/kg streptozotocin (STZ) and the body weight and blood glucose of rats were monitored. After 12-week injection, fluorescein fundus angiography (FFA) and histopathological examination were detected to confirm the successful establishment of DR models. Subsequently, the right eyes of model group rats were conducted retinal laser photocoagulation with the left eyes having no retinal laser photocoagulation and rats of the model group were randomly divided into group B (the model control group), group C (the positive control group), and group D (the DHMMR group), with 10 rats in each group. Rats of the group A and the group B were given vehicle, and the group C were given calcium dobesilate suspension by gavage, and the group D were given DHMMR by gavage. After 4-week gavage, FFA was carried out to observe the fundus microvascular change. Then, the rats were sacrificed to do histopathological examinations and the serum levels of P-selectin, cAMP, cGMP, and the relative expression of the protein of VEGF and PEDF in retina were detected.
    ResultsAfter 12-week STZ injection, the blood glucose of the model group were pronouncedly higher than the blank group (P < 0.01). Fundus micro-hemangioma changes were observed in the rats of the model group through FFA, and the rats of the blank group did not see any changes. The pictures of HE staining showed that the retinal structure of the model group was more disordered than the blank group. After 4-week gavage, treatments with DHMMR showed dramatic reduction of serum levels of P-selectin, cAMP and cGMP compared with the group B (P < 0.01). FFA and histopathological examinations of DHMMR-treated rats revealed significantly suppression of retinal edema, fundus microvascular destruction and retinal destruction distinguishing from the group B. And the relative expression of VEGF protein of the group D and the group A was markedly lower than that of the group B (P < 0.01). The relative expression of PEDF protein of the group D and the group A was dramatically higher than that of the group B to the contrary (P < 0.01).
    ConclusionsDHMMR demonstrates pronounced suppressive effects on the progression of DR after retinal laser photocoagulation, through down-regulating VEGF and up-regulating PEDF.

     

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