穿心蓮內酯減緩神經分支切斷模型誘導的小鼠之病理性疼痛

Andrographolide relieved pathological pain generated by spared nerve injury model in mice

王皇棋(Huang-Chi Wang)

指導教授 ： 李孟真

朝陽科技大學/理工學院/應用化學系生化科技碩博士班/博士(2018年)

摘要

神經病理痛是中樞神經膠細胞為媒介的疼痛訊息途徑失常導致的疾病，
患有神經病理痛的患者會對微小刺激產生不正常疼痛反應。近幾年來緩解
神經病理痛的藥物效果有限且無法長期使用，這使得發展新藥顯得迫切重
要。穿心蓮內酯是穿心蓮中富含之成分，近期研究顯示，穿心蓮內酯可作為
緩解特定疾病的急性疼痛止痛劑；此外，其可在富含星狀細胞的環境中抑制
微膠細胞產生 IL-1 表現，這暗示著穿心蓮內酯可能參與中樞神經膠細胞為
媒介的疼痛訊息途徑。
為了驗證上述假設，本論文於小鼠模型中進行神經分枝切斷誘導產生
病理性疼痛，將小鼠分組、於術後分別以腹腔注射施以食鹽水、穿心蓮內酯
及 NSAIDs 藥物，並使用 von frey hair test 測試小鼠坐骨神經損傷手術導致
的機械性觸感痛行為。結果顯示，經穿心蓮內酯處理的小鼠在手術誘發觸感
痛的疼痛閥值有增加的現象，且可緩解手術患處疼痛以及手術引起的鏡像
疼痛，在手術後的多個行為測試時間點上，穿心蓮內酯緩解觸感痛表現效果
優於 NSAIDs 藥物。與 NSAIDs 藥物相較之下，穿心蓮內酯緩解手術後觸感
痛的效果可延遲至較長的時間(第 14 天)，但 NSAIDs 藥物只能改善短期(第
3 天)疼痛。此外，穿心蓮內酯處理樣品的腰椎第 4-6 節切片中，觀察到了具
下降趨勢的星狀細胞活性與下降的 IL-1 表現量。這暗示著穿心蓮內酯展現
ii
較佳的疼痛緩解效應，具有發展治療病理性疼痛長期療程的新藥物潛在特
性。

關鍵字

止痛長期治療 ； 微膠細胞 ； 星狀細胞 ； 神經病理痛 ； 穿心蓮內酯

並列摘要

Pathological pain is a disease cause by abnormal pain signal transmission
pathway mediated by central glia, the patient suffered from pathological pain
generated abnormal pain response by tiny stimulus. The drugs developed to
release the pathological pain, however, had limited improvement and could not
use in long term treatment. Therefore, it is urgent and important to discover new
drugs for treatment such disease.
Andrographolide(andro) was a composition found in Andrographis
paniculata. In recent study, andro was reported acted as an analgesic agent for
acute pain in some disease. The IL-1 expression in microglia while incubated in
rich astrocytes medium was reduced when treated with andro. Such phenomenon
implied that andro might involve in pain signal transmission pathway mediated
by central glia cell.
In order to confirm this hypothesis, the pathological pain mice model
induced by spared nerve injury was created. After operation, mice were assigned
in groups and respectively treated with saline, andro or NSAIDs by intraperitoneal
injection. The behavior responded form mechanical allodynia induced by spared
nerve injury model was determined by von frey hair test. The results showed that
the increase of withdrawn threshold of allodynia as well as less allodynia behavior
occurred both at operation side and contralateral side were attributed to andro
treatment. Comparing with NSAIDs drugs, andro had better behavior to reduce
allodynia in several detection times. Furthermore, the released allodynia behavior
in mice extended to longer time point (14th day after operation) by andro
treatment, but NSAIDs drugs only released short-term pain (3rd day after
operation). The lower activity of astrocytes association with GFAP and downregulation
of IL-1 expression were observed on the L4-L6 segment of the spinal
cord while treated with andro. These results indicated that andro had behavior to
release the allodynia and had potential in chronic treatment of pathological pain

並列關鍵字

long-term treatment ； microglia ； astrocyte ； pathological pain ； Andrographolide

參考文獻

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