青藤鹼(青藤鹼)是由防己科植物(Sinomenium acutum)根莖所提取之生物鹼。文獻指出青藤鹼具有抗發炎、免疫抑制及鎮痛之作用。然而，其作用的機轉仍不明確。由於青藤鹼的結構式與嗎啡相類似，推測青藤鹼可能為一嗎啡類生物鹼。因此，本研究將探討青藤鹼是否會透過活化嗎啡類受體(opioid receptor)來產生作用。首先，利用已轉植入嗎啡-μ型受體(opioid-μ receptor)的中國倉鼠卵巢細胞(Chinese Hamster Ovary cells, CHO cells )進行放射性受體結合實驗，結果發現隨著青藤鹼的濃度增加，結合於嗎啡-μ型受體上的[3H]naloxone則逐漸減少，顯示青藤鹼具有與嗎啡-μ型受體結合的能力。利用甩尾試驗(tail-flick)發現青藤鹼在小鼠會以劑量相關的方式產生鎮痛效果，而且，青藤鹼無法在嗎啡μ型受體剔除的小鼠(opioid-μ receptor KO mice)產生相同的鎮痛效果。過去研究指出顱腔內注射(intracerebroventricular; i.c.v.) 嗎啡會使正常大鼠體內的血糖上升，並且會增加食慾及產生止痛的功能。本實驗亦將青藤鹼以同樣方式投予至大鼠腦內，發現給予低濃度的青藤鹼會使老鼠體內血糖上升，且此血糖上升的現象會被naloxone及naloxonazine所抑制。不同的是當濃度提高，血糖上升比例則減少。並且，利用高濃度的青藤鹼前處理下可阻斷原本嗎啡所誘導的血糖上升、食慾增加及鎮痛效果的產生。接著，在體外的實驗中，發現青藤鹼在嗎啡μ型受體磷酸化的表現上一樣具有部分致效劑的特性。此外，我們發現前處理30 mg/kg的青藤鹼可以有效減緩嗎啡所造成的疼痛耐受性；在使用100mg/kg高劑量的青藤鹼則可以減少長期使用嗎啡所產生的戒斷症狀(withdrawal symptoms)及心理上的酬賞(rewarding)作用。綜合以上結果，我們推測青藤鹼在嗎啡μ型受體上具有部分致效劑的特性，並且具有發展成為改善嗎啡中毒或成癮之物質的潛力。

Sinomenine is an alkaloid extracted from the roots and stems of Sinomenium acutum. It has been demonstrated to possess analgesia, antiinflammation and immunosuppression. However, the mechanism is still unclear. Due to the sinomenine is similar to morphine in structure, the present study is to investigate the effects of sinomenine via opioid-μ receptor. Results showed decrease of [3H]naloxone binding in parallel with an increase of sinomenine in Chinese Hamster Ovary (CHO) cells transfected with opioid-μ receptor. Using tail-flick test, sinomenine does-dependently produced antinociceptive effects in wild-type mice but not in opioid-μ receptor knockout mice. Similar to morphine,intracerebroventricular administration of sinomenine caused hyperphagia, hyperglycemia and antinociception significantly in rats but which blocked by naloxone or naloxonazine; however, sinomenine at high dose produced antagonism of these effects. In addition, sinomenine showed a partial agonist-like property on the phosphorylation of opioid-μ receptor in CHO cells. Pretreatment with 30 mg/kg sinomenine may delay the analgesic tolerance of morphine, whereas sinomenine at high dose of 100 mg/kg causes attenuation in morphine-induced withdrawal symptoms and rewarding. Taken together, the obtained results suggest that sinomenine has a partial agonist-like action through modulation of opioid-μ receptors showing a potential to be useful for opiate abuse.

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