Neu-P11通过抑制氧化应激降低急性高眼压大鼠眼内压

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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。 Objective Melatonin (Mel) is a class of indole neuroendocrine hormones secreted by the pineal gland. It has a wide range of biological roles in regulating circadian rhythms and antioxidation. The new melatonin nonselective receptor agonist NeuP11 has similar effects to melatonin. The purpose of this paper is to study the effects of Neu-P11 on intraocular pressure in rats with ocular hypertension and its related mechanisms. Methods Thirty healthy 8-week-old SD rats were established by Trendelenburg decubitus position (head low and high 80 ° position). The animals were placed in Trendelenburg decubitus position, with Tonopen XL contact tonometer every 5 min measurement of intraocular pressure 1, take 20 min maximum. After modeling, the rats were randomly divided into 5 groups: normal intraocular pressure + saline group, ocular hypertension + saline group, ocular hypertension +10 mg · kg -1 Mel group, ocular hypertension +20 mg · Kg ~ (-1) Neu-P11 group, ocular hypertension +50 mg · kg -1 Neu-P11 group, with 6 rats in each group. Rest for 2 h after dosing and again for 45 min after being placed in Trendelenburg decubital position for 6 h intraocular pressure (once per hour). One week after continuous administration, SD rats were sacrificed by injection of sodium pentobarbital in excess and blood was taken from the heart to detect the activities of MDA, SOD and GSH-Px in the serum of rats with acute ocular hypertension. Routine histological sections were observed retinal morphological changes in SD rats. Results The intraocular pressure in the Trendelenburg decubitus model group was increased by 202.9% (P <0.01), and the retina was thick and unclear, and the level of oxidative stress was significantly increased. The treatment of Neu-P11 and melatonin, significantly improved the body’s oxidative stress and retinal edema, reduce intraocular pressure in rats. Conclusions Neu-P11 may reduce intraocular pressure in rats with acute ocular hypertension by inhibiting the level of oxidative stress in the body.
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