本文選題：左卡尼汀 + 氧誘導(dǎo)視網(wǎng)膜病變　； 參考：《青島大學(xué)》2012年碩士論文

【摘要】：目的建立氧誘導(dǎo)視網(wǎng)膜病變(OIR)小鼠模型,觀察高氧誘導(dǎo)的視網(wǎng)膜病理改變,并通過腹腔注射不同劑量的左卡尼汀,觀察左卡尼汀是否對病變視網(wǎng)膜具有保護作用。 方法選擇7日齡C57BL/6J小鼠24只,隨機分為正常對照組、高氧模型對照組、低劑量藥物治療組、高劑量藥物治療組,每組6只。除正常對照組外,其余組小鼠置于(75±2)%濃度的氧環(huán)境中飼養(yǎng)5天后,回到正�？諝猸h(huán)境中飼養(yǎng)5天,建立氧誘導(dǎo)視網(wǎng)膜病變動物模型。對藥物治療組小鼠自7日齡起分別給予不同劑量的左卡尼汀,一次/天至小鼠17日齡。另兩組給予相同體積的生理鹽水。每組17日齡小鼠左眼行異硫氰酸葡聚糖熒光素(FITC-Dextran)灌注血管造影視網(wǎng)膜鋪片觀察視網(wǎng)膜血管形態(tài)變化。右眼石蠟切片行蘇木精-伊紅(HE)染色,光學(xué)顯微鏡下觀察并計數(shù)突破視網(wǎng)膜內(nèi)界膜的血管內(nèi)皮細(xì)胞核數(shù)目,免疫組織化學(xué)染色觀察血管內(nèi)皮生長因子(VEGF)在視網(wǎng)膜各層的表達,脫氧核糖核苷酸末端轉(zhuǎn)移酶介導(dǎo)缺口末端標(biāo)記(TUNEL)染色,檢測視網(wǎng)膜神經(jīng)細(xì)胞凋亡數(shù)目。 結(jié)果視網(wǎng)膜鋪片結(jié)果顯示,氧誘導(dǎo)視網(wǎng)膜病變模型鼠的視網(wǎng)膜中央及遠(yuǎn)周見無血管灌注區(qū),周邊部有大量新生血管形成；兩治療組均較高氧模型對照組視網(wǎng)膜血管分布均勻,新生血管和無灌注區(qū)顯著減少。突破內(nèi)界膜的內(nèi)皮細(xì)胞核數(shù)：正常對照組為(0.4833±0.1169),高氧模型對照組為(33.85±2.53),兩者比較有統(tǒng)計學(xué)意義(P0.01)；兩治療組分別為(19.03±4.43)、(12.37±1.62),與高氧模型對照組比較,組間差異具有統(tǒng)計學(xué)意義(F=76.059,P0.01)。兩藥物治療組顯著下調(diào)了VEGF的表達,高劑量藥物治療組效果顯著。兩治療組與高氧模型對照組比較,視網(wǎng)膜神經(jīng)細(xì)胞凋亡數(shù)目顯著減少,組間差異具有統(tǒng)計學(xué)意義(P=129.199,P0.01)。 結(jié)論氧誘導(dǎo)視網(wǎng)膜病變動物模型復(fù)制成功；左卡尼汀在一定程度上改善了OIR小鼠視網(wǎng)膜新生血管增殖情況并減少了視網(wǎng)膜神經(jīng)細(xì)胞凋亡,從而對病變視網(wǎng)膜起保護作用。其機制可能與左卡尼汀抗氧化、清除氧自由基和抗凋亡作用有關(guān)。
[Abstract]:Objective to establish the model of oxygen-induced retinopathy (OIR) mice, observe the pathological changes of the retina induced by hyperoxia, and intraperitoneally inject levacarnitine with different doses. Methods 24 7-day-old C57BL / 6J mice were randomly divided into normal control group, hyperoxia model control group, low dose drug treatment group and high dose drug treatment group. In addition to the normal control group, the other mice were exposed to 75 鹵2% oxygen for 5 days, then returned to the normal air for 5 days to establish the animal model of retinopathy induced by oxygen. The mice in the drug treatment group were given different doses of leucarnitine from 7 days old, once a day to 17 days old. The other two groups were given the same volume of saline. The left eye of each group of 17 days old mice were perfused with FITC-Dextranan (FITC-Dextranan) to observe the morphologic changes of retinal vessels. Paraffin sections of the right eye were stained with hematoxylin and eosin (HEH). The number of vascular endothelial nuclei breaking through the inner membrane of the retina was observed and counted under optical microscope. The expression of vascular endothelial growth factor (VEGF) in all layers of the retina was observed by immunohistochemical staining. Terminal deoxyribonucleotide transferase mediated Nick end labeling (Tunel) staining was used to detect the number of apoptosis in retinal neurons. In oxygen-induced retinopathy model rats, no vascularized area was found in the central and distal retina and a large number of neovascularization was found in the peripheral part of the retina, and the retinal vessels in the two treatment groups were more evenly distributed than those in the hyperoxia model control group. The neovascularization and no perfusion area decreased significantly. The number of endothelial nuclei breaking through the inner boundary membrane was 0.4833 鹵0.1169 in the normal control group and 33.85 鹵2.53 in the hyperoxia model control group, which was significantly higher than that in the control group (19.03 鹵4.43) and the hyperoxia model group (12.37 鹵1.62), respectively. The difference between the two groups was statistically significant compared with the hyperoxia model control group (P 0.01). The expression of VEGF was significantly down-regulated in the two drug treatment groups, and the effect was significant in the high-dose drug treatment group. Compared with the hyperoxia model control group, the number of apoptosis of retinal nerve cells in the two treatment groups was significantly decreased, and the difference between the two groups was statistically significant. Conclusion oxygen induced retinopathy animal model is successful. To a certain extent, L-carnitine improved retinal neovascularization and reduced retinal neuronal apoptosis in OIR mice. The mechanism may be related to the antioxidation, scavenging of oxygen free radicals and anti-apoptotic effects of leucarnitine.
【學(xué)位授予單位】：青島大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號】：R774.1

【參考文獻】

相關(guān)期刊論文 前10條

1 李亞萍,劉早霞,孫大軍,蘇冠方,張曉光;VEGF_(165)單克隆抗體對視網(wǎng)膜新生血管的抑制作用[J];吉林大學(xué)學(xué)報(醫(yī)學(xué)版);2002年06期

2 張志華;蔣犁;喬立興;;血管內(nèi)皮生長因子mRNA在高氧誘導(dǎo)新生鼠視網(wǎng)膜異常新生血管化模型中的表達[J];中國當(dāng)代兒科雜志;2007年04期

3 孔屹,韓麗榮,彭亞軍,唐莉,陳昌秀;尼莫地平與生長因子對視網(wǎng)膜新生血管形成的相互作用[J];第二軍醫(yī)大學(xué)學(xué)報;2005年07期

4 孫景豫,黃維國,王錦玲,邱建華,姜鴻彥;佛波酯對體外培養(yǎng)大鼠前庭上皮PKC表達的影響[J];第四軍醫(yī)大學(xué)學(xué)報;2002年13期

5 張鵬,惠延年,王雨生,張星,劉少山,王海燕;PKC信號傳導(dǎo)通路對缺氧人視網(wǎng)膜色素上皮細(xì)胞表達VEGF的作用[J];第四軍醫(yī)大學(xué)學(xué)報;2003年21期

6 劉鵬飛;惠延年;謝小萍;;促紅細(xì)胞生成素受體抗體抑制小鼠視網(wǎng)膜新生血管形成[J];國際眼科雜志;2008年03期

7 田田;朱小華;;氧化應(yīng)激在視網(wǎng)膜損傷中的作用[J];國際眼科雜志;2009年01期

8 張士勝;廖華萍;王康孫;;高壓氧治療眼科應(yīng)用進展[J];國際眼科雜志;2009年02期

9 底煜;陸巖;王愛媛;楊樝;楊宏偉;陳曉隆;;早產(chǎn)兒視網(wǎng)膜病變研究進展[J];國際眼科雜志;2011年07期

10 涂應(yīng)鋒;王曉云;董建華;肖模超;;左-卡尼汀對兔心肌缺血再灌注損傷的保護作用[J];黑龍江科技信息;2009年03期

，

本文編號：2003735