本文選題：糖尿病 + 視網(wǎng)膜病變��； 參考：《解剖學(xué)報》2017年05期

【摘要】：目的探討NF-E2相關(guān)因子2(Nrf2)對糖尿病視網(wǎng)膜細(xì)胞及血管的保護(hù)作用。方法 8周齡雄性Nrf2~(+/+)(野生型)和Nrf2~(-/-)C57BL/6小鼠60只隨機分為模型組和對照組,共4組,每組各15只。模型組小鼠腹腔注射鏈脲佐菌素(STZ,45mg/kg),連續(xù)注射5 d;對照組小鼠注射同體積的枸櫞酸緩沖液。模型組和對照組小鼠初次注射后每周測空腹血糖及體重,至第10周取視網(wǎng)膜。采用免疫印跡法檢測視網(wǎng)膜內(nèi)Nrf2激活的下游蛋白血紅素加氧酶-1(HO-1)的表達(dá)情況;免疫熒光染色檢測具有多種剪接形式的RNA結(jié)合蛋白(RBPMS)陽性的視網(wǎng)膜節(jié)細(xì)胞(RGCs)及膽堿乙酰轉(zhuǎn)移酶(Ch AT)陽性的無長突細(xì)胞(ACs)并計數(shù);采用過碘酸-希夫和蘇木素染色,觀察視網(wǎng)膜內(nèi)無細(xì)胞毛細(xì)血管并進(jìn)行定量分析。結(jié)果 STZ誘導(dǎo)1周后,野生型和Nrf2~(-/-)模型組小鼠血糖急劇升高,體重開始顯著下降,隨著周齡的增長體重?zé)o明顯增加;對照組小鼠血糖值無明顯升高,體重呈正常緩慢增長趨勢。STZ誘導(dǎo)糖尿病10周后,RBPMS和Ch AT染色發(fā)現(xiàn),Nrf2~(~(-/-))糖尿病小鼠視網(wǎng)膜內(nèi)RGCs和ACs數(shù)量顯著降低(P0.05);過碘酸-希夫和蘇木素染色顯示,Nrf2~(-/-)糖尿病小鼠視網(wǎng)膜內(nèi)出現(xiàn)無細(xì)胞毛細(xì)血管;免疫印跡法顯示,野生型小鼠模型組中Nrf2激活的下游蛋白HO-1表達(dá)升高。結(jié)論 Nrf2對糖尿病視網(wǎng)膜細(xì)胞及血管具有保護(hù)作用,其可能是通過誘導(dǎo)HO-1上調(diào)發(fā)揮作用。
[Abstract]:Objective to investigate the protective effect of NF-E2 related factor 2 nrf 2 on diabetic retinal cells and blood vessels. Methods Sixty 8-week-old male Nrf2G (wild type) and Nrf2~(-/-)C57BL/6 mice were randomly divided into 4 groups (15 in each group) and 4 in model group and control group. The mice in the model group were injected with STZ 45 mg / kg for 5 days and the control group was injected with the same volume of citrate buffer. Fasting blood glucose and body weight were measured weekly after the first injection in the model group and control group, and retina was removed at the 10th week. The expression of heme oxygenase-1 (HO-1), a downstream protein activated by Nrf2 in the retina, was detected by Western blot. Immunofluorescence staining was used to detect and count the RGCs of retinal ganglion cells (RGCs) and choline acetyltransferase (Chat) positive cells of retinal ganglion cells (RGCs) with multiple splicing forms of RNA binding protein (RNA binding protein), and to count them with periodate Schiff and hematoxylin staining. The capillary vessels in the retina were observed and quantitatively analyzed. Results after 1 week of STZ induction, the blood glucose of the wild type and Nrf2 + / -r / -group increased sharply, the body weight began to decrease significantly, and the body weight did not increase with the increase of week age, but the blood sugar value of the control group did not increase significantly. STZ-induced diabetes mellitus 10 weeks later, the number of RGCs and ACs in retina of diabetic mice decreased significantly (P 0.05), and periodate Schiff and hematoxylin staining showed that the visual reticulum of diabetic mice was nrf2r-r-1. Acellular capillaries appeared in the membrane; Western blotting showed that the expression of downstream protein HO-1 activated by Nrf2 was increased in the wild-type mouse model group. Conclusion Nrf2 has protective effect on diabetic retinal cells and blood vessels, which may play a role by inducing up-regulation of HO-1.
【作者單位】： 北京大學(xué)醫(yī)學(xué)部人體解剖學(xué)與組織學(xué)胚胎學(xué)系;
【基金】：國家自然科學(xué)基金青年基金(81200691)
【分類號】：R587.2;R774.1

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