依达拉奉对糖尿病角膜神经病变大鼠角膜神经的保护作用

发布时间：2017-12-31 09:11

本文关键词：依达拉奉对糖尿病角膜神经病变大鼠角膜神经的保护作用　出处：《重庆医科大学》2012年硕士论文　论文类型：学位论文

【摘要】：背景随着糖尿病患者的日益增加，糖尿病性角膜病变越来越受到人们的重视，导致糖尿病角膜病变发病的主要原因为糖尿病引起的角膜神经病变，因此探讨糖尿病角膜神经病变的具体发病机制具有重要意义。目的探讨新型自由基清除剂依达拉奉对糖尿病角膜神经病变大鼠角膜神经的保护作用，研究糖尿病角膜神经病变发病机制中氧化应激的作用。方法健康SD雄性大鼠70只，随机选取20只不做任何处理，作为正常对照组；其余50只采用一次性腹腔注射链脲佐菌素（STZ）（60mg/kg）诱导建立糖尿病大鼠模型，成模后选取血糖值15mmol/L的40只大鼠应用随机数字表法随机分为依达拉奉治疗组（依达拉奉组）和生理盐水对照组（生理盐水组），依达拉奉组每天给予自制的0.2g/L依达拉奉滴眼液点眼，生理盐水组每天给予生理盐水点眼，，每次1滴，每日3次，预防性用药直至实验动物被处死，分别于造模成功后的第6、8、10、12周每组选取5只大鼠，检测角膜知觉后处死大鼠，观察角膜神经形态、角膜神经纤维数量、角膜组织中丙二醛（MDA）含量及超氧化物歧化酶（SOD）活性。结果1.角膜知觉检测：生理盐水组大鼠自造模6周起出现角膜知觉的减退，第12周时角膜知觉减退明显；依达拉奉组第6周时角膜知觉未见明显减退，第8、10、12周角膜知觉较正常对照组减退，但较生理盐水组提高。 2.角膜神经乙酰胆碱酯酶（AChE）染色及形态学观察：生理盐水组自造模后6周起，角膜基质神经干变细、分支减少，上皮下神经网丛密度稀疏、神经活性降低，且随病程延长上述变化日益明显；依达拉奉组较生理盐水组神经形态学明显改善，且神经活性提高。 3.角膜神经纤维计数：生理盐水组大鼠自成模后第6周起，出现角膜神经纤维数量减少，且随病程延长，角膜神经纤维数量减少加剧；依达拉奉组与生理盐水组相比，角膜神经纤维数量明显增多，差异有统计学意义（p0.01）。 4.角膜组织中MDA含量及SOD活性变化：生理盐水组大鼠角膜组织自造模6周起出现MDA含量升高，SOD活性降低，随病程延长变化日益明显；依达拉奉组与生理盐水组比较，角膜组织中MDA含量下降，SOD活性提高，差异有统计学意义（p0.01）。结论1.依达拉奉可降低糖尿病角膜神经病变所致的角膜神经损伤，对神经形态学及功能学起保护作用； 2.氧化应激在糖尿病角膜神经病变的发病机制占有重要地位。
[Abstract]:With the background of diabetes is increasing, diabetic keratopathy has attracted more and more attention, mainly due to the incidence of corneal neuropathy of diabetic keratopathy is caused by diabetes, so to discuss the pathogenesis of diabetic corneal neuropathy has important significance.
Objective to investigate the protective effect of edaravone, a new free radical scavenger, on the corneal nerves in diabetic rats with corneal neuropathy, and to study the role of oxidative stress in the pathogenesis of diabetic corneal neuropathy.
Methods 70 male SD rats, 20 rats were randomly selected without any treatment, as the control group; the remaining 50 by intraperitoneal injection of streptozotocin (STZ) (60mg/kg) induced diabetic rats were induced into the mold after the selection of blood glucose 15mmol/L 40 rats using random number table randomly divided into edaravone group (edaravone group) and saline control group (saline group) and edaravone group were given edaravone 0.2g/L eyedrops and self-made, saline group were given saline drops, 1 drops each time, 3 times daily, preventive medication until the animal was killed, were made after the success of the model 6,8,10,12 weeks of each group 5 rats were selected to detect corneal sensitivity after the rats were sacrificed and the observation of corneal nerve morphology, number of corneal nerve fibers in the corneal tissue malondialdehyde (MDA) content and superoxide dismutase (SOD) Activity.
Results 1. corneal perception test: saline group rats from the model 6 week decline in corneal sensitivity, corneal sensitivity decreased significantly at week twelfth; edaravone group sixth weeks no obvious loss of corneal sensation, 8,10,12 week corneal sensitivity compared with the normal control group decreased, but compared with the saline group.
2. acetylcholinesterase (AChE) staining and corneal nerve morphology: saline group from 6 weeks after operation, corneal stromal neural stem thinning, reduced branches, subepithelial nerve net plexus nerve activity decreased, sparse density, and with the extension of the duration of these changes is more and more obvious; the edaravone group compared with the saline group of nerve morphology significantly improved and the neural activity increased.
3. corneal nerve fiber count: saline group rats into sixth weeks after die, the number of corneal nerve fibers decreased, and with the extension of the course, reduce the number of corneal nerve fibers increased; the edaravone group compared with the saline group, the number of corneal nerve fibers increased significantly, the difference was statistically significant (P0.01).
The change of MDA content and SOD activity of 4. in corneal tissue: physiological saline group rat corneal tissue from the model 6 week MDA content increased, SOD activity decreased with the extension of the course change is more and more obvious; the edaravone group compared with the saline group, MDA decreased in corneal tissue, the activity of SOD increased, the difference was statistically significant (P0.01).
Conclusion edaravone can reduce the injury of corneal nerve 1. diabetic corneal neuropathy caused by the neural morphological and functional study of the protective effect;
2. oxidative stress plays an important role in the pathogenesis of diabetic corneal neuropathy.

【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R587.1;R774.1;R-332

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