Zhang Shu, Chai Fei-Yan, Yan Hong, Guo Yong, Harding J J
Department of Ophthalmology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
Mol Vis. 2008 May 12;14:862-70.
To evaluate the effect of N-acetylcysteine (NAC) and glutathione ethyl ester (GSH-EE) eye drops on the progression of diabetic cataract formation induced by streptozotocin (STZ).
One hundred and thirty Sprague-Dawley (SD) rats were selected, and diabetes was induced by streptozotocin (65 mg/kg bodyweight) in a single intraperitoneal injection. The control group (group I) received only vehicle. Then, 78 rats with random blood glucose above 14 mmol/l were divided into four groups (group II-V). The drug-treated rats received NAC and GSH-EE eye drops five days before STZ injection. Group I and V animals received sodium phosphate buffer drops (pH 7.4), and those in groups II, III, and IV received 0.01% NAC, 0.05% NAC, and 0.1% GSH-EE drops, respectively. Lens transparency was monitored with a slit lamp biomicroscope and classified into six stages. At the end of four weeks, eight weeks, and 13 weeks, animals were killed and components involved in the pathogenesis of diabetic cataract including thiols (from glutathione and protein), glutathione reductase (GR), catalase (CAT), and glycated proteins were investigated in the lens extracts. Blood glucose, urine glucose, and bodyweight were also determined.
The progression in lens opacity induced by diabetes showed a biphasic pattern in which an initial slow increase in the first seven weeks after STZ injection was followed by a rapid increase in the next six weeks. The progression of lens opacity in the treated groups (group II-IV) was slower than that of the untreated group (group V) in the earlier period and especially in the fourth week. There were statistically significant differences between the treated groups and the untreated group (p<0.05). However, these differences became insignificant after the sixth week, and the progression of lens opacification in all diabetic groups became aggravated. The content of thiol (from glutathione and protein), glutathione reductase (GR), and catalase (CAT) were lower in the lens extracts of the diabetic rats four weeks, eight weeks, and 13 weeks after the STZ injection while the levels of thiol and CAT activity were both higher in the treated groups (group II-IV) than in the untreated group (group V) at every stage. However, there was no statistically significant difference (p>0.05). Moreover, the diabetes resulted in an increased level of glycated proteins in both the treated groups and the untreated group, but there was no statistically significant difference between all the diabetic groups (p>0.05).
NAC and GSH-EE can slightly inhibit the progression of the diabetic cataract at the earlier stage. They may maintain lens transparency and function by serving as a precursor for glutathione biosynthesis and by protecting sulfhydryl groups from oxidation.
评估N-乙酰半胱氨酸（NAC）和谷胱甘肽乙酯（GSH-EE）滴眼液对链脲佐菌素（STZ）诱导的糖尿病性白内障形成进展的影响。
选取130只Sprague-Dawley（SD）大鼠，通过单次腹腔注射链脲佐菌素（65mg/kg体重）诱导糖尿病。对照组（I组）仅接受赋形剂。然后，将78只随机血糖高于14mmol/l的大鼠分为四组（II-V组）。药物治疗组大鼠在注射STZ前五天接受NAC和GSH-EE滴眼液。I组和V组动物接受磷酸钠缓冲液滴眼液（pH 7.4），II、III和IV组动物分别接受0.01% NAC、0.05% NAC和0.1% GSH-EE滴眼液。用裂隙灯生物显微镜监测晶状体透明度并分为六个阶段。在四周、八周和十三周结束时，处死动物，研究晶状体提取物中参与糖尿病性白内障发病机制的成分，包括硫醇（来自谷胱甘肽和蛋白质）、谷胱甘肽还原酶（GR）、过氧化氢酶（CAT）和糖化蛋白。还测定血糖、尿糖和体重。
糖尿病诱导的晶状体混浊进展呈双相模式，即STZ注射后前七周最初缓慢增加，随后六周迅速增加。治疗组（II-IV组）晶状体混浊的进展在早期尤其是第四周比未治疗组（V组）慢。治疗组与未治疗组之间存在统计学显著差异（p<0.05）。然而，这些差异在第六周后变得不显著，所有糖尿病组的晶状体混浊进展都加重。STZ注射后四周、八周和十三周，糖尿病大鼠晶状体提取物中的硫醇（来自谷胱甘肽和蛋白质）、谷胱甘肽还原酶（GR）和过氧化氢酶（CAT）含量较低，而在每个阶段，治疗组（II-IV组）的硫醇水平和CAT活性均高于未治疗组（V组）。然而，没有统计学显著差异（p>0.05）。此外，糖尿病导致治疗组和未治疗组的糖化蛋白水平均升高，但所有糖尿病组之间没有统计学显著差异（p>0.05）。
NAC和GSH-EE在早期可轻微抑制糖尿病性白内障的进展。它们可能通过作为谷胱甘肽生物合成的前体并保护巯基免受氧化来维持晶状体透明度和功能。
