Hong Tang-Yao, Tzeng Thing-Fong, Liou Shorong-Shii, Liu I-Min
Department of Biotechnology, Collage of Pharmacy and Health Care, Tajen University, Taiwan, R.O.C.
Department of Pharmacy and Master Program, Tajen University, Taiwan, R.O.C.
Vascul Pharmacol. 2016 Jan;76:18-27. doi: 10.1016/j.vph.2015.08.015. Epub 2015 Aug 28.
Diabetic retinopathy (DR) is a common diabetic eye disease which is well-known as the result of microvascular retinal changes. Although the ethanol extract from Zingiber zerumbet (L.) Smith rhizome (EEZZR) has been indicated to ameliorate hyperglycemia in diabetes, its protective effect on DR remains unclear. The aim of this study was to determine the effects of EEZZR on DR in streptozotocin (STZ) diabetic rats. Diabetic rats were treated orally with EEZZR (200, 300 mg/kg per day) or calcium dobesilate (CD; 500 mg/kg per day) for 12 weeks. EEZZR displayed similar characteristics to CD in reducing blood-retinal barrier permeability in diabetic rats. Retinal histopathological observation showed that retinal vessels were decreased in EEZZR-treated diabetic rats. EEZZR decreased the increased retinal expression of vascular endothelial growth factor (VEGF) and upregulate the expressions of renal pigment epithelium-derived factor (PEDF) in diabetic rats. Retinal mRNA expression of tumor necrosis factor-α, interleukin (IL)-1, IL-6, monocyte chemotactic proteins-1, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 were all decreased in EEZZR-treated diabetic rats. Moreover, EEZZR could attenuate phosphorylation of nuclear factor Kappa B (NF-κB) p65 and extracellular signal-regulated kinase (ERK)1/2 as well as inhibit the nuclear translocation of pNF-κB p65 induced by diabetes. In conclusion, restoring the balance between stimulators and inhibitors of angiogenesis may be associated with the protective effect of EEZZR on DR. In addition, EEZZR can ameliorate retinal inflammation via transrepression of NF-κB and inhibition of ERK1/2 signaling pathway.
糖尿病视网膜病变(DR)是一种常见的糖尿病眼部疾病,因视网膜微血管变化而闻名。虽然已表明从红球姜根茎中提取的乙醇提取物(EEZZR)可改善糖尿病中的高血糖症,但其对DR的保护作用仍不清楚。本研究的目的是确定EEZZR对链脲佐菌素(STZ)诱导的糖尿病大鼠DR的影响。糖尿病大鼠口服EEZZR(每天200、300毫克/千克)或羟苯磺酸钙(CD;每天500毫克/千克),持续12周。EEZZR在降低糖尿病大鼠血视网膜屏障通透性方面表现出与CD相似的特征。视网膜组织病理学观察显示,EEZZR治疗的糖尿病大鼠视网膜血管减少。EEZZR降低了糖尿病大鼠视网膜中血管内皮生长因子(VEGF)表达的增加,并上调了肾色素上皮衍生因子(PEDF)的表达。EEZZR治疗的糖尿病大鼠视网膜中肿瘤坏死因子-α、白细胞介素(IL)-1、IL-6、单核细胞趋化蛋白-1、细胞间黏附分子-1和血管细胞黏附分子-1的mRNA表达均降低。此外,EEZZR可减弱核因子κB(NF-κB)p65和细胞外信号调节激酶(ERK)1/2的磷酸化,并抑制糖尿病诱导的pNF-κB p65核转位。总之,恢复血管生成刺激因子和抑制因子之间的平衡可能与EEZZR对DR的保护作用有关。此外,EEZZR可通过NF-κB的反式抑制和ERK1/2信号通路的抑制来改善视网膜炎症。