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t al. Dobesilate enhances endothelial nitric oxide synthaseactivity in macro and microvascular endothelial cells. Br J Pharmacol. 1997。122(7):15028. 16. Vojnikovic B. Doxium (calcium dobesilate) reduces blood hyperviscosity and lowers elevated intraocular pressure in patients with diabetic retinopathy and glaucoma. Ophthalmic Res. 1991。23(1):1220.,第十九頁,共三十七頁。,導升明174。:預防血視網(wǎng)膜屏障(p237。ngzh224。ng)損傷15,17,預防血視網(wǎng)膜損傷:預防外膜細胞凋亡;穩(wěn)固內皮細胞間緊密連接;降低視網(wǎng)膜血管滲透性,防止(f225。ngzhǐ)滲漏,15. Leal EC, et al. Calcium dobesilate inhibits the alterations in tight junction proteins and leukocyte adhesion to retinal endothelial cells induced by diabetes. Diabetes. 2010。59(10):263745. 17. Rota R, et al. Reduction of retinal albumin leakage by the antioxidant calcium dobesilate in streptozotocindiabetic rats. Eur J Pharmacol. 2004 Jul 14。495(23):21724.,第二十頁,共三十七頁。,導升明174。:防止(f225。ngzhǐ)新生血管形成18,防止新生(xīnshēng)血管形成:抑制VEGF和FGF產(chǎn)生,預防新生血管生成;降低高滲透性和血管滲漏,18. Angulo J, et al. Inhibition of vascular endothelial growth factor (VEGF)induced endothelial proliferation, arterial relaxation, vascular permeability and angiogenesis by dobesilate. Eur J Pharmacol. 2011 Sep 30。667(13):1539.,第二十一頁,共三十七頁。,導升明174。對早期糖尿病視網(wǎng)膜病變(b236。ngbi224。n)進展的影響19,目的:旨在明確羥苯磺酸鈣(CaD)與安慰劑相比對早期糖尿病視網(wǎng)膜病變(DR)中血視網(wǎng)膜屏障(BRB)的影響。 設計:隨機、雙盲、安慰劑對照研究。 人群(r233。nqn):194例2型糖尿病患者(CaD組為98例,安慰劑組為96例),其中137例完成24個月的研究(CaD組為69例,安慰劑組為68例)。 方法:患者接受CaD(2g,每日一次)或安慰劑治療24個月。 主要終點:每6個月使用熒光光度測定法評估PVPR。,19. Ribeiro ML, et al. Effect of calcium dobesilate on progression of early diabetic retinopathy: a randomised doubleblind study. Graefes Arch Clin Exp Ophthalmol. 2006。244(12):1591600.,第二十二頁,共三十七頁。,研究人群人口統(tǒng)計學和基線(jīxi224。n)特征19,BMI,體重指數(shù);HbA1c,糖化血紅蛋白;IOP,眼內壓;PVPR,玻璃體后滲透率;DR水平,根據(jù)ETDRS量表確定(qu232。d236。ng)的糖尿病視網(wǎng)膜病變級別。,19. Ribeiro ML, et al. Effec