摘要
目的褪黑素(melatonin,Mel)是由松果体分泌的一类吲哚类神经内分泌激素,具有调节昼夜节律和抗氧化等广泛的生物学作用。新型褪黑素非选择性受体激动剂NeuP11与褪黑素作用相似。该文旨在研究Neu-P11对急性高眼压大鼠眼内压的影响及其相关机制。方法采用Trendelenburg卧位(头低脚高80°位置)法将30只健康8周龄SD大鼠建立急性高眼压模型,即动物被置于Trendelenburg卧位,用Tonopen XL接触眼压计每5 min测量1次眼内压,取20 min最大值。建模后将大鼠随机分为5组:正常眼压+生理盐水组、高眼压+生理盐水组、高眼压+10 mg·kg^(-1)Mel组、高眼压+20 mg·kg^(-1)Neu-P11组、高眼压+50 mg·kg^(-1)Neu-P11组,每组6只。给药后平位休息2 h,再次置于Trendelenburg卧位45 min后,连续监测6 h眼内压(每小时1次)。连续给药1周后,注射过量戊巴比妥钠处死SD大鼠,心脏取血,检测急性高眼压大鼠血清中MDA、SOD和GSH-Px的活性;留取各组大鼠眼球进行常规组织学切片,观察SD大鼠视网膜形态学变化。结果 Trendelenburg卧位诱导模型组大鼠眼内压值比正常组升高了约202.9%(P<0.01),且视网膜增厚,层次不清,机体氧化应激水平明显升高。而经Neu-P11和褪黑素治疗后,明显改善了机体氧化应激水平和视网膜水肿,降低大鼠眼内压。结论 Neu-P11可能通过抑制机体氧化应激水平,降低急性高眼压大鼠眼内压。
Aim To explore the effect of Neu-P11, a novel melatonin agonist with similar function of melatonin, on IOP of acute high IOP animals and the related mechanism.Methods The experiment used the Trendelenburg position（head low feet high position of 80°）to establish acute high IOP model.Rats were placed in the Trendelenburg position and used Tonopen XL contact tonometer to measure IOP（every 5 minutes measured once IOP, and the maximum value in 20 minutes）in 8：00-9：00 am.And then, thirty Sprague-Dawley rats（8 week-old）were divided into five groups： normal IOP＋normal saline, high IOP＋normal saline, high IOP＋10 mg·kg^-1 Mel, high IOP＋20 mg·kg^-1 Neu-P11, high IOP＋50 mg·kg^-1 Neu-P11.Put in a flat to rest 2 h, animals were placed in Trendelenburg position again and then, IOP was measured every hour in the flat by 6 hours.After excessive sodium pentobarbital administration continuous for 1 week, the serum was collected and stored for subsequent detection at the end of the experiment.The level of MDA, SOD and GSH-Px enzyme activity of the rat serum was tested by kit accordingly.HE staining method was used to identify the SD rat retinal morphological changes.Results Trendelenburg position could induce IOP of model group rats, which was increased by 202.9%（P〈0.01）and the content of MDA, reduced the activity of SOD and GSH-Px enzyme, retinal thickening was observed and its level was not clear.Neu-P11/Mel could significantly improve oxidative stress level and retinal edema in rats.Conclusion Neu-P11 could reduce IOP of the acute high IOP animals, which might be involved in the lower level of oxidative stress in the body.
作者
石金凤
张星慧
李美香
佘美华
贺鹏程
田期先
Moshe Laudon
尹卫东
张瑶
SHI Jin-feng ZHANG Xing-hui LI Mei-xiang SHE Mei-hua HE Peng-cheng TIAN Qi-xian Moshe Laudon YIN Wei-dong ZHANG Yao(Institute of Cardiovascular Disease Dept of Biotechnology,Institute of Pharmaceutical and Biological Sciences,University of South China, Hengyang Hunan 421001,China Aier Eye Hospital of Hengyang,Hengyang Hunan 421001,China the First People＇s Hospital of Changde,Changde Hunan 415000,China Neurim Pharmaceuticals Ltd, Israel)
出处
《中国药理学通报》
CAS
CSCD
北大核心
2017年第5期637-641,共5页
Chinese Pharmacological Bulletin
基金
湖南省自然科学基金资助项目(No 14JJ2084)
湖南省教育厅基金项目(No 15C1203)
湖南省卫生计生委基金(No C2015-19)
南华大学‘蒸湘学者计划'资助(Xiangyang Tang)
关键词
Neu-P11
褪黑素
眼内压
特伦德伦伯卧位
MDA
SOD
GSH-PX
Neu-P11
melatonin
intraocular pressure
Trendelenburg position
malondialdehyde
superoxide dismutase
glutathion peroxidase
