玻璃酸钠(HA),是一种直链结构的高分子多糖,广泛分布于动物和人体结缔组织细胞外基质中,具有非常好的生物相容性。玻璃酸钠独特的多糖链海绵网状结构使其具有强大的锁水能力并可作为缓慢释放水分子的“蓄水池”。因此玻璃酸钠滴眼液被广泛用于干眼并成为干眼治疗的一线用药。此外,最近的研究也表明,玻璃酸钠滴眼液可以促进角膜上皮愈合从而保护眼表上皮。但是玻璃酸钠滴眼液是否对糖尿病相关眼表疾病有效依然未知。
近日,来自山东省眼科研究所的周庆军教授带领他的团队评估了0.3%玻璃酸钠、0.1%玻璃酸钠以及0.4%聚乙二醇用于糖尿病相关眼表疾病的治疗效果并将研究结果发表在Cornea杂志上。
此项研究将造模得到的糖尿病小鼠随机分为5组,每组各20只,各组分别使用不同的滴眼液进行治疗,每天滴眼4次,共滴眼10天。评估眼表的不规则变化、角膜上皮损伤愈合率、角膜敏感性、神经纤维密度、结膜杯状细胞数量以及MUC-5AC黏蛋白含量。
研究结果
0.3%玻璃酸钠组角膜上皮损伤愈合率在损伤24及48小时后均显著高于糖尿病对照组。角膜上皮损伤14天后,0.3%玻璃酸钠组与糖尿病对照组相比角膜点状染色明显减少。
糖尿病小鼠角膜神经再生及知觉恢复延迟,而0.3%玻璃酸钠治疗7天后,可增加角膜基底下神经纤维的密度并改善角膜知觉,与糖尿病对照组相比有显著统计学差异。
与正常组相比,糖尿病小鼠结膜杯状细胞数量下降,而0.3%玻璃酸钠治疗组的结膜杯状细胞平均数量明显增加,并恢复到正常组的水平。
与正常组相比,糖尿病小鼠结膜上皮MUC-5AC蛋白染色密度及含量明显减低,但是0.3%玻璃酸钠组与糖尿病对照组相比可显著增加MUC-5AC蛋白的表达水平。
周庆军教授在研究结论中指出,高浓度玻璃酸钠滴眼液可以促进角膜上皮再生,加快角膜上皮损伤愈合;增加角膜神经纤维密度和敏感性,促进角膜神经再生,改善眼表状况;显著增加杯状细胞的数量和黏蛋白的表达,提高泪膜的稳定性、减少角膜表面不规则性,改善干眼症状。0.3%高浓度玻璃酸钠可能有助于改善糖尿病患者眼表慢性损伤,并且其疗效优于0.1%玻璃酸钠和聚乙二醇滴眼液。
原文摘要
Cornea. 2017 Sep;36(9):1133-1138.
Efficacy of Sodium Hyaluronate in Murine DiabeticOcular Surface Diseases.
Di G, Qi X, Zhao X, Zhang S, Zhou Q.
Abstract
PURPOSE:
Toevaluate the efficacy of sodium hyaluronate (HA) eye drops for the treatment ofdiabetic ocular surface diseases in mice.
METHODS:
Male6- to 8-week-old C57BL/6 mice underwent induction of type 1 diabetes withintraperitoneal injections of streptozotocin, with normal mice as the control.Topical 0.3% HA, 0.1% HA, 0.4% polyethylene glycol eye drops, and normal salinewere administered to diabetic mice with an intact or debrided cornealepithelium. Normal saline was applied in the controls. Corneal epithelial woundhealing rate, corneal sensation, nerve fiber density, conjunctival goblet cellnumber, and MUC-5AC content were measured and compared.
RESULTS:
Comparedwith the controls, topical 0.3% HA use in diabetic mice showed significantimprovements in the corneal epithelial wound healing rate (48 hours: 91.5% ±4.8% vs. 79.8% ± 6.1%; P < 0.05), corneal sensitivity (4.1 ± 0.3 cm vs. 3.5± 0.3 cm; P < 0.05), nerve fiber density (12.9% ± 2.3% vs. 6.6% ± 2.4%; P< 0.05), conjunctival goblet cell number (31.0 ± 8.4/100 μm vs. 19.6 ±7.1/100 μm; P < 0.05), and MUC-5AC content (12.5 ± 1.4 ng/mg vs. 7.8 ± 1.5ng/mg protein; P < 0.05). The beneficial effects of 0.3% HA were better thanthose of 0.1% HA and 0.4% polyethylene glycol.
CONCLUSIONS:
Topical0.3% HA treatment promoted corneal epithelial regeneration, improved cornealsensation, and increased density of corneal nerve fibers and conjunctivalgoblet cells in mice with diabetic ocular surface diseases.
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PMID:28644234