【摘要】：目的： 研究吡哆胺對糖尿病大鼠視網(wǎng)膜中晚期糖基化終末產(chǎn)物(AGEs)及其受體(RAGE)表達的影響，探討吡哆胺在保護糖尿病大鼠視網(wǎng)膜中的作用。 方法： 將6周齡（清潔級）雄性SD大鼠以單次腹腔注射鏈脲佐菌素(STZ)誘發(fā)為1型糖尿病。實驗大鼠分為4組，①吡哆胺處理組（PM組）：STZ注射72h后采用吡哆胺（200mg·kg-1·d-1）灌胃；②氨基胍處理組（AG組）：STZ注射72h后采用氨基胍(100mg·kg-1·d-1)灌胃；③對照組（DM組）：STZ注射72h后采用蒸餾水(2ml/d)灌胃；④正常對照組（NC組）：正常大鼠檸檬酸緩沖液注射72h后采用蒸餾水(2ml/d)灌胃。治療4周和12周后取大鼠血清和視網(wǎng)膜，采用ELISA法測定AGEs含量，使用免疫熒光染色和實時熒光定量PCR觀察視網(wǎng)膜中RAGE的分布和表達情況。結果：治療4周時，ELISA檢測各組血清和視網(wǎng)膜AGEs含量結果顯示：PM組為2.430±0.096ug/l，2.406±0.118ug/l；AG組為3.360±0.110ug/l，3.324±0.110ug/l；DM組為3.789±0.128ug/l，3.811±0.130ug/l；PM組與AG組和DM組比較差異有統(tǒng)計學意義（P0.01）。治療12周時，各組血清和視網(wǎng)膜AGEs含量結果： PM組為2.934±0.061ug/l，2.909±0.055ug/l；AG組為3.888±0.080ug/l，3.812±0.120ug/l；DM組為4.327±0.100ug/l，4.367±0.103ug/l；PM組與AG組和DM組比較差異有統(tǒng)計學意義（P0.01）。12周時各組AGEs含量比4周時明顯增加（P0.01）。免疫熒光染色檢測發(fā)現(xiàn)RAGE表達于視網(wǎng)膜色素上皮層至神經(jīng)節(jié)細胞層，治療4周時OD值分別為PM組1.72±0.04，AG組1.56±0.04，DM組1.30±0.02，，PM組與AG組和DM組比較差異有統(tǒng)計學意義（P0.01）。治療12周時OD值分別為PM組1.52±0.22，AG組1.37±0.26，DM組1.00±0.02，PM組與AG組和DM組比較差異有統(tǒng)計學意義（P0.01）。12周時各組RAGE表達量明顯高于4周時（P0.01）。實時熒光定量PCR對RAGE mRNA的檢測結果趨勢同免疫熒光染色結果一致。 結論： 使用吡哆胺治療能降低糖尿病大鼠血清和視網(wǎng)膜AGEs的含量，并下調(diào)其受體RAGE的表達，減輕二者對視網(wǎng)膜產(chǎn)生的毒性損害，具有保護視網(wǎng)膜的作用。
[Abstract]:Aim: to study the effect of pyridoxamine on the expression of (AGEs) and its receptor (RAGE) in the late stage of diabetic rat retina, and to explore the role of pyridoxamine in protecting the retina of diabetic rats. Methods: 6 weeks old male SD rats were induced into type 1 diabetes mellitus by single intraperitoneal injection of streptozotocin (STZ). The experimental rats were divided into 4 groups. 1 the rats in the PM group were treated with pyridoxamine (200mg kg-1 d-1) for 72 h after): STZ injection. 2Aminoguanidine treated group (AG group) was treated with 100mg kg-1 d-1 after 72 h of): STZ injection, and control group (DM group) was treated with distilled water (2ml/d) 72 h after): STZ injection. 4 normal control group (NC group): normal rats were treated with distilled water (2ml/d) for 72 h after injection of citric acid buffer. After 4 and 12 weeks of treatment, the serum and retina of the rats were taken. The content of AGEs was measured by ELISA method. The distribution and expression of RAGE in the retina were observed by immunofluorescence staining and real-time fluorescence quantitative PCR. Results: at 4 weeks after treatment, the serum and retinal AGEs levels in the PM group were 2.430 鹵0.096ugP / L 2.406 鹵0.118ugP / L + AG = 3.360 鹵0.110ugP / L = 3.324 鹵0.110ugP / L, respectively. There was significant difference between DM group and AG group and DM group (3.789 鹵0.128ugP / L = 3.811 鹵0.130ugP / L) (P0.01). After 12 weeks of treatment, the serum and retinal AGEs levels in the PM group were 2.934 鹵0.061ugP / L 2.909 鹵0.055ugP / L AG, 3.888 鹵0.080ugP / L = 3.812 鹵0.120ugP / L, and 4.327 鹵0.100ugP / L = 4.367 鹵0.103ugP / l, respectively, in the PM group (4.327 鹵0.100ugP / L = 4.367 鹵0.103ugP / l). The content of AGEs in PM group was significantly higher than that in AG group and DM group at 12 weeks (P0.01). Immunofluorescence staining showed that RAGE was expressed in the retinal pigment epithelium layer to the ganglion cell layer. The OD values at 4 weeks after treatment were 1.72 鹵0.04 AG in PM group 1.56 鹵0.04 渭 m in DM group and 1.30 鹵0.02 in DM group, respectively. There was significant difference between PM group and AG group and DM group (P0.01). At 12 weeks after treatment, the OD values of PM group were 1.52 鹵0.22 AG group 1.37 鹵0.26 渭 g DM group 1.00 鹵0.02, respectively. The expression of RAGE in PM group was significantly higher than that in AG group and DM group at 12 weeks (P0.01). The trend of RAGE mRNA detection by real-time fluorescence quantitative PCR was consistent with that of immunofluorescence staining. Conclusion: the treatment of pyridoxamine can reduce the content of AGEs in serum and retina of diabetic rats, and down-regulate the expression of RAGE receptor, alleviate the toxic damage to retina and protect the retina.
【學位授予單位】：福建醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2012
【分類號】：R774.1

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