本文選題：脊髓損傷　切入點(diǎn)：IL-1β　引自：《重慶醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的探討IL-1β對(duì)脊髓損傷后膠質(zhì)纖維酸性蛋白(glial fibrillary acidic protein,GFAP)及波形蛋白(Vimentin)表達(dá)的影響及JAK2-STAT3信號(hào)通路在其中發(fā)揮的作用。方法(1)建立大鼠急性脊髓損傷模型,按不同的干預(yù)措施將大鼠隨機(jī)分為模型組(model group)、假手術(shù)組(sham group)、IL-1β特異性抑制劑組(IL-1RA group)、IL-1β組(IL-1βgroup)。分別于建模后大鼠的脊髓損傷處給予生理鹽水、IL-1RA、IL-1β各10ul,假手術(shù)組只打開椎板,不作其他處理。各組大鼠在術(shù)后相應(yīng)時(shí)間點(diǎn)(術(shù)后8h、12h、1天、3天、7天、14天)利用BBB評(píng)分測定其運(yùn)動(dòng)障礙程度,運(yùn)用Western blotting、免疫熒光、免疫組化等技術(shù)觀察各處理組間相關(guān)指標(biāo)(GFAP、p-STAT3)的變化趨勢。(2)建立大鼠急性脊髓損傷模型,按不同的干預(yù)措施將大鼠隨機(jī)分為模型組(model group)、假手術(shù)組(sham group)、IL-1β+JAK2-STAT3特異性抑制劑組(IL-1β+AG490 group)、IL-1β組(IL-1βgroup)。分別于建模后大鼠的脊髓損傷處給予生理鹽水、IL-1β+AG490、IL-1β各10ul,假手術(shù)組只打開椎板,不作其他處理。各組大鼠在術(shù)后相應(yīng)時(shí)間點(diǎn)(術(shù)后1、3、7、14天)利用BBB評(píng)分測定其運(yùn)動(dòng)障礙程度,運(yùn)用Western blotting、免疫熒光等技術(shù)檢測各處理組間相關(guān)指標(biāo)(GFAP、Vimentin)的變化趨勢。結(jié)果(1)術(shù)后第8h、12h,IL-1β特異性抑制劑組p-STAT3表達(dá)相比模型組顯著降低(p0.05),IL-1β組p-STAT3表達(dá)相比模型組顯著升高(p0.05),各處理組p-STAT3表達(dá)相比假手術(shù)組均顯著升高(p0.01)。術(shù)后第7、14天,IL-1β特異性抑制劑組GFAP表達(dá)相比模型組顯著降低(p0.05),IL-1β組GFAP表達(dá)相比模型組顯著升高(p0.05),各處理組GFAP表達(dá)相比假手術(shù)組均顯著升高(p0.01)。術(shù)后第14天,IL-1β特異性抑制劑組BBB評(píng)分相比模型組顯著提高(p0.05),IL-1β組BBB評(píng)分相比模型組顯著降低(p0.05),各處理組BBB評(píng)分相比假手術(shù)組均顯著降低(p0.01)。術(shù)后第1、3天,各組GFAP表達(dá)相較模型組無顯著差異;術(shù)后第1、3、7天,各組BBB評(píng)分相較模型組無顯著差異(p0.05)。術(shù)后第7、14天,IL-1β+AG490組GFAP、Vimentin表達(dá)相比模型組顯著降低(p0.05),IL-1β組GFAP、Vimentin表達(dá)相比模型組顯著升高(p0.05),各處理組GFAP、Vimentin表達(dá)相比假手術(shù)組均顯著升高(p0.01)。術(shù)后第14天,IL-1β+AG490組BBB評(píng)分相比模型組顯著提高(p0.05),IL-1β組BBB評(píng)分相比模型組顯著降低(p0.05),各處理組BBB評(píng)分相比假手術(shù)組均顯著降低(p0.01)。術(shù)后第1、3天,各組GFAP、Vimentin表達(dá)相較模型組無顯著差異;術(shù)后第1、3、7天,各組BBB評(píng)分相較模型組無顯著差異(p0.05)。結(jié)論急性脊髓損傷后分泌的IL-1β可通過磷酸化JAK2-STAT3促進(jìn)損傷局部膠質(zhì)瘢痕形成,進(jìn)而影響大鼠后肢運(yùn)動(dòng)功能。
[Abstract]:Objective to investigate the effect of IL-1 尾 on the expression of glial fibrillary acidic protein (GFAP) and vimentin (Vimentin) after spinal cord injury (sci) and the role of JAK2-STAT3 signaling pathway.Methods A rat model of acute spinal cord injury was established. Rats were randomly divided into two groups according to different intervention measures: model group, sham group, IL-1 尾 specific inhibitor group, IL-1RA group and IL-1 尾 group.The rats were given normal saline IL-1RA-IL-1 尾 at the spinal cord injury area after modeling, and the sham operation group only opened the lamina without any other treatment.The degree of motor dysfunction was measured by BBB score, Western blotting and immunofluorescence were used to measure the degree of motor dysfunction at the corresponding time points (8 h, 12 h, 1 day, 3 days and 14 days after operation).The rats were given normal saline IL-1 尾 AG490 and IL-1 尾 10 ul. the sham operation group only opened the lamina without any other treatment.BBB scores were used to measure the degree of motor dysfunction at the corresponding time points (1 day 3 days after operation), and Western blotting, immunofluorescence and other techniques were used to detect the change trend of the relative indexes of each treatment group.Results (1) the expression of p-STAT3 in IL-1- 尾 specific inhibitor group was significantly lower than that in model group at 8 h after operation. Compared with model group, the expression of p-STAT3 in IL-1 尾 group was significantly higher than that in model group. The p-STAT3 expression in each treatment group was significantly higher than that in sham operation group.The expression of GFAP in the IL-1 尾 specific inhibitor group was significantly lower than that in the model group on the 7th day after operation. Compared with the model group, the expression of GFAP in the IL-1 尾 group was significantly higher than that in the model group. The GFAP expression in each treatment group was significantly higher than that in the sham operation group.On the 14th day after operation, the BBB score of IL-1 尾 specific inhibitor group was significantly higher than that of model group. Compared with model group, the BBB score of IL-1 尾 group was significantly lower than that of model group, and the BBB score of each treatment group was significantly lower than that of sham operation group.On the 1st day after operation, the expression of GFAP in each group was not significantly different from that in the model group, but on the 3rd day after operation, there was no significant difference in BBB score between each group and the model group (P 0.05).On the 14th day after operation, the BBB score of IL-1 尾 AG490 group was significantly higher than that of model group. Compared with model group, the BBB score of IL-1 尾 group was significantly lower than that of model group. The BBB score of each treatment group was significantly lower than that of sham operation group.On the 1st day after operation, there was no significant difference in the expression of Vimentin in each group as compared with the model group, but on the 3rd day after operation, there was no significant difference in BBB score between each group and the model group (p0.05).Conclusion IL-1 尾 secreted after acute spinal cord injury can promote the formation of local glial scar by phosphorylated JAK2-STAT3, and then affect the motor function of hindlimb in rats.
【學(xué)位授予單位】：重慶醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R651.2

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