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The Effect Of Octreotide And Nitric Oxide In Retinal Ishcemia-reperfusion Injury

Posted on:2008-09-05Degree:MasterType:Thesis
Country:ChinaCandidate:Y L BianFull Text:PDF
GTID:2144360212496187Subject:Clinical Medicine
Abstract/Summary:PDF Full Text Request
Retinal ischemia reperfusion disease is a common eye disease in clinic, and also is one of the main blinding ophthalmopathy. It can cause varying degrees of retinal ischemia. After reperfusion the retina suffers more serious injury, and causes the decline of visual funtion. Therefore, we pay more attention to the injury of retinal ischemia-reperfusion and the study of its prevention and treatment, increasingly.Retinal ischemia reperfusion injury, which occurs in the result of many factors including the role of free radicals, intracellular calcium overload and microvascular injury and the role of leukocyte etc, produces cell death by destruction of cellular elements such as DNA, protein and cell membrane. Nitric oxide, a micromolecular endogenous gas which plays a role as neurotransmitter intracellular and intercellular, plays an important role in the control of ocular vascular tone and blood flow as it is a potent signaling molecule in blood vessels, where a continuous formation from endothelial cells maintains vasodilatation and blood flow and it also affects the vascular system through its ability to inhibit platelet aggregation and adhesion. The iNOS produces NO, then NO plays a part in pathological conditions such as tissue injury. The Ca-independent iNOS has been reported to be induced by macrophages, neutrophils and other cells responding to inflammatory stimuli and PMNLs generate NO via a pathway in which L-arginine has been metabolized. Therefore, nitric oxide plays a very important role in retinal ischemia-reperfusion disease.Octreotide, the synthetic analogue of natural somatostatin, can reduce both the expression of iNOS and the level of NO2-/NO3-, which are the metabolites ofthe NO in the ischemia reperfusion injury of pancreas, as well as it can inhibit the retinal neovascularization in diabetic retinopathy. But there is no report about whether octrotide have therapeutical effect on the injury of the retinal ischemia reperfusion in our country.Objective: To investigate the effect of octreotide on electroretinogram, histopathological damage and the change of nitric oxide activity after retinal ischemia-reperfusion injury, we try to find whether octreotide have effect on the injury of the retinal ischemia reperfusion injury and the activity of nitric oxide. Method: Three groups were formed from 21 guinea pigs and each of the groups included seven animals:Control group: no drug was used and I/R was not inducedIschemia group: I/R was induced and normal saline was administered. Ischemia /octreotide group: I/R was induced and octreotide was administered. 90minutes of pressure-induced retinal ischemia and 24 h of reperfusion were established in the ischemia and ischemia/octreotide groups. 1 ml of normal saline was injected intraperitoneally 15 min prior the ischemic insult to the animals of the ischemia group and it was repeated five times with 6-h intervals and 50μg/kg of octreotide was administered via the same route five times with 6-h intervals, similarly the first dose being injected 15 min before the ischemic insult in the ischemia/octreotide group. After 24 h of reperfusion, ERG was recorded in both eyes of all rats.After the examination of ERG, the animals were reanesthetized and both eyes of all the animals including the controls were rapidly enucleated. One eye of each animal was randomly selected for biochemical assay and the other for histopathological evaluation. Retinal nitrate oxide levels were measured andhistopathological changes were evaluated in the groups.Result: 1.ERG: There were differences among the three groups without exception. 2.The level of NO: The mean retinal nitrate oxide levels of the control, ischemia and ischemia/octreotide groups were 0.74065±0.03486, 1.63234±0.30571, 0.93261±0.05499, respectively. Nitrate oxide levels of ischemia group increased significantly versus control and ischemia/octreotide groups. Though the level of nitric oxide in ischemia/octreotide group is more or less higher than the control group, there was no difference between them.3.Histopathological changes in retina: In the ischemia group, retinal histopathological changes, which were different from the control group, were karyopycnosis and vacuolated spaces in RGCL; tissue looseness and atrophy in IPL and OPL; edema and decrease of cells in INL and ONL. No changes except mild edema in RGCL and IPL, was observed in the retina of the ischemia/octreotide group.Conclusion: (1)Octreotide could ameliorate the change of ERG in retinal ischemia reperfusion injury in a certain extent. (2)The level of nitric oxide increased, in the same time octreotide could decrease the level of nitric oxide and reduce its toxicity to the retina, in retinal ischemia reperfusion injury. (3) Octreotide could ameliorate the injury of retinal ischemia reperfusion.
Keywords/Search Tags:octreotide, nitric oxide, retina, ischemia, reperfusion
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