發(fā)布時(shí)間：2018-10-17 09:09

【摘要】：目的探討普羅布考預(yù)處理對(duì)視網(wǎng)膜缺血再灌注(retina ischemia reperfusion, RIR)損傷的保護(hù)作用及機(jī)制。 方法成年雄性無眼疾的wistar大鼠隨機(jī)分成正常對(duì)照組,缺血對(duì)照組和預(yù)處理組。所有大鼠普通飼料喂養(yǎng)2周,正常對(duì)照組和缺血對(duì)照組按5m1/Kg體重予生理鹽水灌胃2次／天,預(yù)處理組按5m1/Kg體重予普羅布考混懸液灌胃2次／天。缺血對(duì)照組和預(yù)處理組大鼠右眼前房灌注生理鹽水形成14.3KPa高眼壓,缺血60分后恢復(fù)血流,建立RIR損傷模型。分別于再灌注后1h、6h、12h、24h.48H、72h頸椎脫臼法隨機(jī)處死缺血對(duì)照組和預(yù)處理組大鼠各10只,制備視網(wǎng)膜組織切片和視網(wǎng)膜組織勻漿。光學(xué)顯微鏡下觀察視網(wǎng)膜組織學(xué)變化,脫氧核糖核苷酸末端轉(zhuǎn)移酶介導(dǎo)的缺口末端標(biāo)記法(TUNEL)原位檢測(cè)視網(wǎng)膜神經(jīng)元細(xì)胞的凋亡情況,分光光度法測(cè)定視網(wǎng)膜組織MDA含量及SOD活性水平。 結(jié)果(1)大鼠視網(wǎng)膜缺血再灌注后早期視網(wǎng)膜內(nèi)層水腫增厚,晚期視網(wǎng)膜內(nèi)層萎縮變薄；預(yù)處理組同缺血對(duì)照組比較,缺血再灌注早期水腫較輕,晚期視網(wǎng)膜內(nèi)層萎縮程度輕(P0.05)。(2)正常對(duì)照組視網(wǎng)膜中凋亡細(xì)胞少見；缺血再灌注后6h開始有凋亡細(xì)胞陽性表達(dá),24h凋亡細(xì)胞陽性表達(dá)達(dá)頂峰；預(yù)處理組細(xì)胞凋亡改變出現(xiàn)同缺血對(duì)照組相似的趨勢(shì)j再灌注6h后各期凋亡陽性細(xì)胞數(shù)明顯少于缺血對(duì)照組(P0.05)。(3)大鼠視網(wǎng)膜缺血再灌注后,缺血對(duì)照組視網(wǎng)膜內(nèi)MDA含量逐漸上升,再灌注6h后含量較正常對(duì)照組高(P0.05)；預(yù)處理組視網(wǎng)膜MDA含量變化趨勢(shì)同缺血對(duì)照組,再灌注6h后各時(shí)間點(diǎn)視網(wǎng)膜MDA含量均較缺血對(duì)照組低(P0.05)。視網(wǎng)膜缺血再灌注后,缺血對(duì)照組視網(wǎng)膜內(nèi)SOD活性水平逐漸下降,6h后活性水平明顯低于正常對(duì)照組(P0.01)；預(yù)處理組再灌注后SOD活性水平高于缺血對(duì)照組,再灌注后1h、6h、12h、24h比較有明顯差異(P0.05)。 結(jié)論普羅布考預(yù)處理能夠減輕大鼠視網(wǎng)膜缺血再灌注損傷,其保護(hù)機(jī)制可能與其能夠減少缺血再灌注后神經(jīng)元的凋亡,提高視網(wǎng)膜組織抗氧化能力,降低視網(wǎng)膜組織脂質(zhì)過氧化物的形成有關(guān)。
[Abstract]:Objective to investigate the protective effect and mechanism of probucol preconditioning on retinal ischemia reperfusion (retina ischemia reperfusion, RIR) injury. Methods Adult male wistar rats without eye disease were randomly divided into normal control group, ischemic control group and preconditioning group. All rats were fed with normal diet for 2 weeks, the normal control group and ischemic control group were given normal saline twice a day according to 5m1/Kg body weight, and the pretreatment group received probucol suspension twice a day according to 5m1/Kg body weight. Rats in ischemic control group and preconditioning group were perfused with normal saline in right anterior chamber to form high intraocular pressure (IOP) and recovered blood flow after ischemia for 60 minutes to establish RIR injury model. One hour after reperfusion, 10 rats in the ischemic control group and 10 rats in the preconditioning group were randomly killed at 12 h, 24 h, 48 h and 72 h after reperfusion to prepare retinal tissue sections and retinal homogenate. The histological changes of retina were observed under optical microscope. The apoptosis of retinal neurons was detected by deoxyribonucleotide terminal transferase-mediated Nick end labeling (TUNEL) in situ. The content of MDA and the activity of SOD in retina were measured by spectrophotometry. Results (1) the edema of the inner layer of retina was thickened at the early stage and the inner layer of the retina shrank in the late stage after ischemia reperfusion in rats, and the edema in the preconditioning group was lighter than that in the ischemic control group. The degree of late retinal inner layer atrophy was light (P0.05). (2) the apoptotic cells were rare in normal control group, the positive expression of apoptotic cells began 6 hours after ischemia and reperfusion, and the positive expression of apoptotic cells reached the peak at 24 h after reperfusion. The changes of apoptosis in preconditioning group were similar to those in ischemic control group. The number of apoptotic positive cells in each phase of preconditioning group was significantly lower than that in ischemic control group (P0.05). (3). The content of MDA in retina of ischemic control group increased gradually. The content of retinal MDA in preconditioning group was the same as that in ischemic control group after 6 h reperfusion (P0.05), and the MDA content in retina of preconditioning group was lower than that of ischemic control group at 6 h after reperfusion (P0.05). The level of SOD activity in the retina of the ischemic control group decreased gradually after ischemia reperfusion, and was significantly lower than that in the normal control group after 6 hours (P0.01), and the activity level of SOD in the preconditioning group was higher than that in the ischemic control group after reperfusion. There was a significant difference (P 0.05) between 12 h and 12 h after reperfusion (P 0.05). Conclusion Probucol preconditioning can reduce retinal ischemia-reperfusion injury in rats, and its protective mechanism may be similar to that of probucol preconditioning to reduce neuronal apoptosis and increase the antioxidant capacity of retinal tissue after ischemia-reperfusion. It is related to reducing the formation of lipid peroxide in retina.
【學(xué)位授予單位】：青島大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2012
【分類號(hào)】：R774.1

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