紫蘇萃取物對脂多糖所誘發的小鼠神經膠細胞發炎之抗發炎機轉研究

Investigating anti-inflammatory effects of Perilla Frutescens on Lipopolysaccharide-stimulated murine microglial cell BV-2

李孟鳳(Meng-Feng Li)

指導教授 ： 高紹軒

中山醫學大學/醫學科技學院/醫學檢驗暨生物技術學系碩士班/碩士(2012年)

摘要

微膠細胞是中樞神經系統中主要的免疫細胞之一，當環境變化或外在刺激，如感染、發炎、中風，即會造成微膠細胞活化，活化的微膠細胞具有吞噬及分泌促發炎物質的能力，扮演中樞神經系統的免疫調控角色，但持續或過度的活化卻會造成中樞神經系統傷害。本實驗以小鼠微膠細胞株BV-2為實驗材料，利用細菌脂多醣 (LPS)刺激微膠細胞活化，以探討紫蘇萃物抗發炎作用及機轉。
在本研究中我們發現以『5，10，30，50μg/ml』濃度的Perilla Frutescens可降低脂多醣體引發的發炎因子，包含 iNOS 以及 COX-2等訊息核酸及蛋白質的生成。並發現Perilla Frutescens也會降低NO的產生。由此，我們更進一步探討Perilla Frutescens抑制脂多醣體所造成的發炎反應是否透過MAPKs和PI3K / Akt路徑。確實發現可以降低脂多醣體所誘導的磷酸化Akt和MAPK家族(包含了ERK、JNK、P38 ) 。此外，也發現Perilla Frutescens抗發炎的效果，是經由影響NF-κB無法轉入到細胞核內，而抑制轉錄因子NF-κB訊息的活化。綜合以上結果，可以得知在Perilla Frutescens的給予下，明顯降低脂多醣體所誘導的前發炎的因子如IL-6和TNF-α 的mRNA，是透過抑制MAPK家族和AKT這兩條路徑，使NF-κB無法轉錄到細胞核內，而抑制下游的發炎基因無法開啟

關鍵字

紫蘇萃取物 ； 脂多糖 ； 小鼠神經膠細胞

並列摘要

Microglia cell is one of the important immune cells in central nervous system. Microglia cells can be stimulated by several environments, for instance, infection, inflammation or even stroke. During the status of stimulating, microglia cells have the ability in phagocytosis and secret pro-inflammatory factors, in order to play a role of regulation in central nervous system. However, continuous or over acting might be harmful to the central nervous system In this experiment, we decide to use the BV-2, a microglia cell line of mice, as a material, by the using LPS to stimulate microglia cells and reveal the mechanism and inflammation effect in relationship of Perilla Frutescens. In this study we found that Perilla Frutescens can decrease the pro-inflammatory factors by LPS in the concentration 5, 10, 30 and 50μg/ml. Meanwhile, Perilla Frutescens can trigger the synthesis of iNOS and COX-2, and the signal transduction in anti-inflammation is through NO pathway by Perilla Frutescens. Thus, to achieve that, we further discussed the pro-inflammatory factors by LPS in microglial cells. As the result, we found that Perilla Frutescens could inhibit the inflammation by effected the PI3K/AKT pathways, and confirmed that the decreasing of AKT and MAPK super-families by the treatment of Perilla Frutescens. Besides, Perilla Frutescens can inhibit NF-κB in translocating into nuclei and down regulate the inflammation.
In conclusion, we know during the treatment of Perilla Frutescens, pro-inflammatory factors, such as IL-6 or TNF-α, would be down regulated, and by the blocking the signal transduction of MAPK and AKT pathways, stop the translocating of NF-κB, then eventurally attenuate the inflammation.

並列關鍵字

Perilla Frutescens ； LPS ； microglial cell BV-2

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