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  • 學位論文

D-半乳糖誘發小鼠老化之免疫反應研究

The study of immune responses on D-galactose induced aging mice

指導教授 : 陳妙齡

摘要


免疫系統是人體重要的防禦系統,已知老化會導致免疫系統的功能減弱,且有文獻指出D-半乳糖會誘導自由基的增加、抗氧化酵素的活性降低和腦神經化學的變化,跟自然老化很相似,但在免疫反應之研究仍十分缺乏,因此本研究以D-半乳糖誘發BALB/c小鼠和C57BL/6j小鼠老化,探討老化小鼠全身性免疫反應之變化。 首先,採用BALB/c小鼠分為三組,模式控制組、Gal-100和Gal-150組分別每天注射0、100和150 mg/Kg的D-半乳糖連續八週,並飼養自然老化鼠作為模式建立之對比。結果顯示,D-半乳糖注射可誘導Aβ 42含量增加;免疫反應方面,D-半乳糖注射下,腦部IL-6濃度與Aβ 42呈現正相關,血清促發炎性細胞激素含量上升,顯示D-半乳糖注射對BALB/c小鼠免疫反應的影響主要在於,增加促發炎性反應;在氧化及抗氧化指標方面,腎臟TBARS含量增加,腦部、肝臟GSH含量增加及肝臟SOD的活性增加。 首先,採用C57BL/6j小鼠分為四組,為模式控制組、Gal-100、Gal-150、Gal-500組分別每天注射0、100、150、500 mg/Kg的D-半乳糖連續八週,並飼養自然老化鼠作為模式建立之對比。結果顯示,Gal-500組會導致Aβ 42顯著增加,相對的活動力顯著降低。此外,注射150 mg/Kg的D-半乳糖小鼠腦均質液TNF-α濃度顯著較高,但Gal-500組無顯著差異。此外, 500 mg/Kg的D-半乳糖注射會降低脾臟細胞的T輔助型細胞、抗原呈現細胞和巨噬細胞的活性。 綜合本研究之結果得知,給予BALB/c小鼠注射150 mg/Kg的D-半乳糖誘發老化,增加促發炎性細胞激素生成,C57BL/6j小鼠注射500 mg/Kg的D-半乳糖確實誘發老化,降低淋巴結抗原呈獻細胞與T細胞比例,亦加促發炎性細胞激素生成,可作為老化下免疫調節相關研究之誘發方法。

關鍵字

D-半乳糖 老化 免疫

並列摘要


Age-related changes of the immune system contribute to the increased susceptibility of elderly persons to infectious diseases. Mice chronically injected with D-galactose (D-gal) have been used as an animal aging model. However, less attention has been paid to the changes of immune responses on D-gal induced aging mice. To investigate the changes of immune responses on D-gal injected aging mice, the BALB/c and C57BL/6j were used in this study. First, BALB/c mice of model control (MC), Gal-100 and Gal-150 groups were subcutaneous injected with 0, 100 and 150 mg/Kg/day for 8 weeks, individually, and compared with nature aging mice (NA) in this study. The brain and supernatants form immune cell culture were collected for cytokines assay. The Aβ42 in brain homogenates and serum IL-6 levels from the BALB/c mice injected with 150 mg/Kg/day D-gal significantly higher than MC group, as well as IL-6 production from peritoneal macrophages and IL-4 secretion from splenocytes. The indicators of oxidation and antioxidant, kidney TBARS content increased, brain and liver GSH content increased, and the liver SOD activity increased. The C57BL/6J mice of model control (MC), Gal-100,Gal-150 and Gal-500 groups were subcutaneous injected with 0, 100 , 150 and 500 mg/Kg/day for 8 weeks. The brain and supernatants form immune cell culture were collected for cytokines assay. The results indicated that Aβ42 were significantly increased in brain from Gal-500 group, opposite to the activity of the mice. Furthermore, 150 mg/Kg/day D-galinjected mice had higher cytokines production, especially TNF-α level in brain homogenates, but not in Gal-500 group. Moreover, D-gal injection decreased the IL-2 secretion, and increased the IL-4 production by splenocytes, but not reach significantly effects. 500 mg/Kg/day D-gal injection reduced CD4 and MHC-II expression in splenocytes, as well as actived macrophages. To summary the results of this study, BALB/c mice injected with 150 mg/Kg D-gal could induce Aβ and pro-inflammatory cytokines production. C57BL/6j mice injected with 500 mg/Kg D-gal could induce aging responses and pro-inflammatory cytokines production, but decrease antigen presenting cell and T cell population. This study demonstrated that mice injected with D-gal can be use as the immune-regulatory study of aging.

並列關鍵字

D-galactose aging immune

參考文獻


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