兰州大学机构库 >学院待认领
PPAR-γ激动剂对大鼠角膜碱烧伤后NF-κB和TNF-α表达的影响
Alternative TitleEffects of peroxisome proliferators-activated receptor-γ agonist on expression of NF-κB and TNF-α in alkali-burned corneal of rat
赵楠楠
Thesis Advisor鲁建华 ; 张文芳
2010-05-24
Degree Grantor兰州大学
Place of Conferral兰州
Degree Name硕士
KeywordPPAR-γ激动剂 吡格列酮 碱烧伤 核因子-κB 肿瘤坏死因子-α
Abstract目的 探讨眼局部应用过氧化物酶体增殖物激活受体(peroxisome proliferator-activated receptor gamma , PPAR-γ)激动剂吡格列酮(Pioglitazone)对大鼠角膜碱烧伤后核转录因子-kappaB (nuclear factor- kappa B,NF-κB)和肿瘤坏死因子-alpha(tumor necrosis factor-alpha,TNF-α)表达的影响。方法 48只健康SPF级SD大鼠角膜碱烧伤后随机分组,每组12只鼠(12只眼),Ⅰ组为烧伤治疗组(ⅠA低剂量组;ⅠB高剂量组),分别结膜下注射0.2g/L、0.8g/L吡格列酮0.1ml,每天1次。Ⅱ组为治疗对照组,结膜下注射地塞米松,0.5mg 0.1ml,每天1次。Ⅲ组为空白对照组,结膜下注射生理盐水0.1ml,每天1次。所有大鼠右眼为实验眼,左眼作为阴性对照。均连续用药2周。动态检测碱烧伤后第1天、第4天、第7天、第14天的角膜新生血管(corneal neovascularization,CNV)的发展,以及观察PPAR-γ、NF-κB和TNF-α在各时间段的表达。结果 PPAR-γ自烧伤第1天开始表达,随着CNV的发生发展,PPAR-γ、NF--κB、TNF-α的表达呈上升趋势。ⅠB组CNV发生率相比较Ⅱ组、Ⅲ组明显延迟、生长抑制;IA组与Ⅱ组两组间相比,差异无统计学意义(P>0.05)。ⅠB组在第4、7、14天CNV生长面积分别为:(5.42±0.25 )mm2<上标!>、(8.14±0.25)mm2<上标!>、(9.67±0.42)mm2<上标!>,组间相比差异均有显著统计学意义(均为P<0.05);碱烧伤后第7天ⅠB组PPAR-γ的表达较Ⅱ组、Ⅲ组明显上升,NF--κB、TNF-α表达均有不同程度的下降,差异均有统计学意义(P<0.05)。 结论 PPAR-γ激动剂吡格列酮抑制大鼠CNV的生成,减轻炎性反应且与剂量浓度有关。其机制可能与活化后的PPAR-γ,在炎症早期有效阻止NF-κB活化,降低TNF-α表达有关。
Other AbstractObjective To investigate the ocular application of peroxisome proliferators -activated receptor gamma (PPAR-γ) agonist pioglitazone on expression of NF-κB and TNF-α in alkali-burned corneal of rat. Methods After corneal alkali-burn models 48 Sprayue-Dawley rats were established, The rats were randomly divided into 3groups, GroupⅠ for burned treatment group (ⅠA: low-dose group, 0.2g/L;ⅠB: high-dose group, 0.8g/L ), PPAR-γ agonist Pioglitazone of different concentrations were injected at the same way in ⅠA、ⅠB groups respectively for once per day. GroupⅡ for the treatment of the control group, Subconjunctival injection of dexamethasone for once per day. Ⅰ-Ⅱ groups of medication lasts 2 weeks. Normal saline was subconjunctivally injected after burning of cornea in control groupⅢ. All of right eyes for the experimental eye, and left eyes as a negative control. The growth of CNV in 48 SD rats was observed by slit lamp microscope and the area of CNV was recorded.The expression of PPAR-γ、NF-κB and TNF-α were detected by immunohistochemistry.Results PPAR-γ was not expressed in normal rat cornea. Corneal angiogenesis was observed after alkali-burned corneas of rats, and reached the peak after 4 to 7 days.The expression of PPAR-γ was positively correlated to CNV and the expressions of NF-κB and TNF-α. The corneal neovascularization area in groupⅠB was significantly smaller than that in the control groupsⅡ、Ⅲ(P<0.05).Compared with groupsⅡ、Ⅲ,the occurence and the growth of CNV in groupⅠB were inhibited obviousily.But no difference betweenⅠA group and Ⅱgroup(P>0.05). On the 4 th,7 th,14th day,the neovasctdarization area in theⅠB group were(5.42±0.25 )mm2<上标!>、(8.14±0.25)mm2<上标!>、(9.67±0.42)mm2<上标!>, respectively. The difference was highly significant(P<0.05). more expression of PPAR-γ in theⅠB group,and the expressions of NF-κB and TNF-α were statistically declined in varying degrees and at different times (P<0.05).Conclusion PPAR-γ agonist Pioglitazone can reduce the inflammatory response of rats after alkali burn, and inhibit the growth of CNV. The mechanism may be related to activation of PPAR-γ, which reduced pro-inflammatory factor TNF-α, and inhibited of activation of NF-κB.
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Language中文
Document Type学位论文
Identifierhttps://ir.lzu.edu.cn/handle/262010/223967
Collection学院待认领
Affiliation临床医学院
Recommended Citation
GB/T 7714
赵楠楠. PPAR-γ激动剂对大鼠角膜碱烧伤后NF-κB和TNF-α表达的影响[D]. 兰州. 兰州大学,2010.
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