N-乙酰-L-半胱氨酸抗1型糖尿病模型比格犬晶状体上皮氧化损伤的作用

doi:10.11843/j.issn.0366-6964.2023.01.033

Abstract

Abstract: This study aimed to investigate the effect of N-acetyl-L-cysteine (NAC) on oxidative damage of lens epithelium in the beagle model of type 1 diabetes mellitus. Forty beagles, 2-3 years old, were randomly divided into control group (CON group), diabetes model group (DM group), insulin treatment group (INS group), NAC combined with insulin treatment group (NAC+INS group) and NAC treatment group (NAC group), 8 dogs in each group. The establishment of experimental dog model in each treatment group lasted for 120 days. Before and after modeling, insulin release test, fasting blood glucose and aqueous humor glucose were tested and cataract grade evaluation was carried out by slit lamp. The lens epithelium was histopathologically observed, and ELISA and RT-PCR detected the oxidative stress index and inflammatory factors in the lens. The results of insulin release test and fasting blood glucose showed that the model of type 1 diabetes beagle was established successfully; Compared with CON group, at the end of the experiment, the serum and aqueous glucose of DM group increased significantly (P<0.05), and the lens function decreased significantly; Slit-lamp results showed that the lens opacity of the DM group reached grade IV at the end of the experiment, while the other four groups showed no apparent signs of cortical opacity; In addition, obvious pathological changes such as nuclear pyknosis and necrotic bodies were observed in the lens epithelium of DM group; Blood glucose in NAC, INS and NAC+INS groups showed a downward trend，but was still higher than that in CON group; The blood glucose in NAC+INS group was significantly lower than that in DM group (P<0.05); and the lens opacity was also significantly improved; At the end of the experiment, compared with CON group，in the canine crystal epithelium and aqueous fluid, MDA content of DM group increased (P<0.05 or P<0.01), while GSH-Px activity and GSH/GSSG all had the noteworthy decrease (P<0.05 or P<0.01), GR activity decreased (P>0.05 in crystal epithelium; P<0.01 in aqueous fluid); After treatment of NAC combined with insulin, oxidative stress markers in crystal epithelium showed an opposite trend. The expression levels of SOD₂ and GR in DM group and all treatment groups were significantly increased (P<0.05). In conclusion, therapy of NAC combined with insulin has improvement for glycemic control and lens function in diabetic dogs, the protective effect of NAC combined with insulin on lens epithelial injury in diabetic dogs may be related to the inhibition of oxidative stress of the lens.

Key words: canine type 1 diabetes mellitus, diabetic cataract, lens epithelial cells, oxidative stress, N-acetyl-L-cysteine

CLC Number:

S856.5

ZHOU Shuilian, BAI Yuman, XIE Wenting, HUANG Jianjia, QIU Wenyue, PANG Xiaoyue, ZHANG Xinting, TANG Zhaoxin, SU Rongsheng. Effect of N-acetyl-L-cysteine on Oxidative Damage of Lens Epithelium in Beagle Dogs with Type 1 Diabetes Mellitus[J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(1): 361-370.

References 22

[1]	FOSTER N C, BECK R W, MILLER K M, et al. State of type 1 diabetes management and outcomes from the T1D exchange in 2016-2018[J]. Diabetes Technol Ther, 2019, 21(2):66-72.
[2]	KUMAR P A, REDDY P Y, SRINIVAS P N B S, et al. Delay of diabetic cataract in rats by the antiglycating potential of cumin through modulation of α-crystallin chaperone activity[J]. J Nutr Biochem, 2009, 20(7):553-562.
[3]	沈卫峰, 宁光. 糖尿病与心血管疾病[M]. 上海:上海科技教育出版社, 2006:333.SHEN W F, NING G. Diabetes mellitus and cardiovascular disease[M]. Shanghai:Shanghai Science and Technology Education Press, 2006:333. (in Chinese)
[4]	杨沛方, 陈祥, 周志楠, 等. N-乙酰半胱氨酸对山羊子宫内膜基质细胞增殖及相关基因表达的影响[J]. 畜牧兽医学报, 2022, 53(1):141-150.YANG P F, CHEN X, ZHOU Z N, et al. The effect of N-acetylcysteine on proliferation and related gene expression of goat endometrial stromal cells in vitro[J]. Acta Veterinaria et Zootechnica Sinica, 2022, 53(1):141-150. (in Chinese)
[5]	钱韦昊, 李绍波, 路会侠. N-乙酰-L-半胱氨酸对子宫内膜异位症自噬及活性氧的影响[J]. 中国临床药理学杂志, 2019, 35(18):2125-2127.QIAN W H, LI S B, LU H X. Effect of N-acetyl-L-cysteine on autophagy and reactive oxygen species in endometriosis[J]. The Chinese Journal of Clinical Pharmacology, 2019, 35(18):2125-2127. (in Chinese)
[6]	秦淑兰, 宁红红, 朱艳, 等. NAC抗氧化应激治疗对糖尿病小鼠骨髓干细胞增殖和凋亡的影响[J]. 山东医药, 2021, 61(14):41-44.QIN S L, NING H H, ZHU Y, et al. Effects of NAC anti-oxidant therapy on proliferation and apoptosis of bone marrow stem cells in diabetic mice[J]. Shandong Medical Journal, 2021, 61(14):41-44. (in Chinese)
[7]	严刚. 糖尿病合并重症肺炎患者行雾化乙酰半胱氨酸对IL-6、TNF-a的影响研究[J]. 糖尿病新世界, 2021, 24(6):75-77.YAN G. Study on the effect of nebulized acetylcysteine on IL-6 and TNF-a in patients with diabetes and severe pneumonia[J]. Diabetes New World, 2021, 24(6):75-77. (in Chinese)
[8]	东彦新, 魏艳辉. 宠物犬糖尿病研究进展[J]. 现代畜牧科技, 2018(12):1-4.DONG Y X, WEI Y H. Research progress of pet dog diabetes mellitus[J]. Modern Animal Husbandry Science & Technology, 2018(12):1-4. (in Chinese)
[9]	AO S, KIKUCHI C, ONO T, et al. Effect of instillation of aldose reductase inhibitor FR74366 on diabetic cataract[J]. Invest Ophthalmol Vis Sci, 1991, 32(12):3078-3083.
[10]	MILLER K M, BECK R W, BERGENSTAL R M, et al. Evidence of a strong association between frequency of self-monitoring of blood glucose and hemoglobin A1c levels in T1D exchange clinic registry participants[J]. Diabetes Care, 2013, 36(7):2009-2014.
[11]	WOOD J R, MILLER K M, MAAHS D M, et al. Most youth with type 1 diabetes in the T1D exchange clinic registry do not meet American diabetes association or international society for pediatric and adolescent diabetes clinical guidelines[J]. Diabetes Care, 2013, 36(7):2035-2037.
[12]	张志鹏. 犬三种白内障模型的建立和氧化损伤性白内障发展进程中AQPO表达的研究[D].重庆:西南大学,2015.ZHANG Z P. Establishment three kinds models of cataract and study on AQPO expression in oxidative damage cataract in canine[D]. Chongqing:Southwest University, 2015. (in Chinese)
[13]	OISHI N, MORIKUBO S, TAKAMURA Y, et al. Correlation between adult diabetic cataracts and red blood cell aldose reductase levels[J]. Invest Ophthalmol Vis Sci, 2006, 47(5):2061-2064.
[14]	BEEBE D C, HOLEKAMP N M, SHUI Y B. Oxidative damage and the prevention of age-related cataracts[J]. Ophthalmic Res, 2010, 44(3):155-165.
[15]	BABIZHAYEV M A, VISHNYAKOVA K S, YEGOROV Y E. Telomere-dependent senescent phenotype of lens epithelial cells as a biological marker of aging and cataractogenesis:the role of oxidative stress intensity and specific mechanism of phospholipid hydroperoxide toxicity in lens and aqueous[J]. Fundam Clin Pharmacol, 2011, 25(2):139-162.
[16]	SZKUDELSKI T. The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas[J]. Physiol Res, 2001, 50(6):537-546.
[17]	BOARESCU P M, BOARESCU I, POP R M, et al. Evaluation of oxidative stress biomarkers, pro-inflammatory cytokines, and histological changes in experimental hypertension, dyslipidemia, and type 1 diabetes mellitus[J]. Int J Mol Sci, 2022, 23(3):1438.
[18]	何慧. 氧化应激与PECAM-1对糖尿病大鼠血管的影响及普罗布考的干预研究[D]. 长沙:中南大学,2010.HE H. The effect of oxidative stress and PECAM-1 on the aorta of diabetic rats and the intervention study of Probucol[D]. Changsha:Central South University, 2010. (in Chinese)
[19]	WU Z M, YIN X X, JI L, et al. Ginkgo biloba extract prevents against apoptosis induced by high glucose in human lens epithelial cells[J]. Acta Pharmacol Sin, 2008, 29(9):1042-1050.
[20]	DOS TENÓRIO M C, GRACILIANO N G, MOURA F A, et al. N-acetylcysteine (Nac):impacts on human health[J]. Antioxidants, 2021, 10(6):967.
[21]	WANG F X, MA J, HAN F, et al. DL-3-n-butylphthalide delays the onset and progression of diabetic cataract by inhibiting oxidative stress in rat diabetic model[J]. Sci Rep, 2016, 6(1):19396.
[22]	TAKAHASHI P, XAVIER D J, LIMA J E B F, et al. Transcript expression profiles and microRNA regulation indicate an upregulation of processes linked to oxidative stress, DNA repair, cell death, and inflammation in type 1 diabetes mellitus patients[J]. J Diabetes Res, 2022, 2022:3511329.

Effect of N-acetyl-L-cysteine on Oxidative Damage of Lens Epithelium in Beagle Dogs with Type 1 Diabetes Mellitus

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