竇狀隙阻塞症候群為一種由化療藥物或含有吡咯啶生物鹼的植物所引起的肝病變，會使竇狀隙內皮細胞型態改變，引起血球阻塞及白血球浸潤，並促進發炎反應，進而使肝臟產生氧化壓力。褪黑激素為一種有效的抗氧化劑，可預防急性肝損傷；然而褪黑激素對於竇狀隙阻塞症候群之作用尚不清楚，因此本研究主要目的為探討褪黑激素對於野百合鹼所誘發小鼠竇狀隙阻塞症候群之作用。本實驗動物品系使用C57BL/6JNarl雄性小鼠，以腹腔注射方式施打褪黑激素(1-30 mg/kg)至小鼠體內，等待1小時後，注射野百合鹼(500 mg/kg)以誘導竇狀隙阻塞症候群，經過24小時後將小鼠犧牲，採集實驗動物之血液及肝臟進行後續分析。為探討肝臟之損傷，分別進行血清生化值及血球計數分析，並以切片染色評估肝臟組織變化，另測量膠原蛋白、氧化壓力指標、抗氧化能力及細胞凋亡路徑相關蛋白之表現量。由實驗結果顯示，對於竇狀隙阻塞症候群，褪黑激素會加劇肝臟受損的程度。其損傷包括增加肝指數血液麩胺酸草醋酸轉氨酶(GOT)、麩丙酮酸轉氨酶(GPT)、血液中嗜中性白血球、肝臟受損面積、血小板聚集、氧化壓力指標；此外降低血液中紅血球、血球容積比、血小板和淋巴球及肝臟中膠原蛋白、抗氧化能力；並激活細胞凋亡路徑。綜合上述結果，褪黑激素對於竇狀隙阻塞症候群不具有保護作用。此外，褪黑激素可能透過小鼠肝臟血小板聚集、氧化壓力增加，進一步激活細胞凋亡路徑，造成由野百合鹼所誘發之小鼠竇狀隙阻塞症候群之肝臟損傷更加嚴重。

Sinusoidal obstruction syndrome (SOS) is a chemotherapeutic drug or pyrrolizidine alkaloid (PA) plant-induced liver injury. SOS is characterized by rounding and swelling of the sinusoidal endothelial cell, which leads to obstruction of blood vessels, leukocyte infiltration, inflammation and oxidative stress in the liver. In addition, melatonin (MEL), a powerful antioxidant, can prevent acute liver injury. However, the role of MEL on SOS has never been investigated. The aim of this study was to investigate the effect of MEL on monocrotaline (MCT)-induced SOS in mice. Male C57BL/6JNarl mice were injected with a single dose (500 mg/kg) of MCT to induce SOS. MEL (1-30 mg/kg) was injected 1 h before MCT treatment. After 24 h of MCT treatment, mice were sacrificed. The blood and liver were collected. Organ damage was evaluated by serum biochemistry, hematology analyzer and histological examination. Hepatic collagen, oxidative stress, antioxidant activity and the expression of apoptosis protein were measured. MEL exacerbated MCT-induced SOS. In addition, it not only increased serum glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), neutrophil count, histological score, hepatic platelet aggregation, oxidative stress and activated of apoptosis signaling pathway, but also decreased red blood cell count, hematocrit ratio, platelet count, lymphocyte count, hepatic collagen, antioxidant activity. To conclude, MEL did not have protective effect on SOS. In addition, MEL exacerbates MCT-induced SOS via hepatic platelet aggregation and oxidative stress, ultimately leading to activation of apoptosis.

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