探討冬蟲夏草菌絲體於硫代乙醯胺誘導肝損傷下護肝功效

Abstract

肝纖維化 (liver fibrosis) 源於慢性肝損傷，這會使肝星狀細胞活化並分泌胞外基質 (Extracellular matrix, ECM)。在組織學上，肝纖維化過去被認為是被動而不可逆的過程，但1970年代之臨床報告指出該病症具有可逆的潛力，目前則以損傷與癒合模式看待此類病症。 本研究設計參考衛福部公告之護肝功能評估方法來探討人工培養之冬蟲夏草菌絲體 (Ophiocordyceps sinensis mycelium, OSM) 對於硫代乙醯胺 (thioacetamide, TAA) 誘導下肝纖維化與慢性肝損傷之保護作用。試驗之結果證實：冬蟲夏草菌絲體粉末在以TAA誘導大鼠之模式中可藉由改善肝臟脂質恆定而減少脂肪堆積，並提高其抗氧化能力，減緩因TAA造成的肝損傷。實驗結果中指出經TAA處理之大鼠補充OSM，可以降低肝臟大小(p < 0.05)及血液生化值中的AST和ALT (p < 0.05)；TAA所造成的低血脂現象亦顯著地回復(p < 0.05)，且肝組織中脂質氧化程度(TBARS)減少，抗氧化能力(TEAC、SOD、CAT、GPx)顯著的上升(p < 0.05)；在發炎相關細胞激素(TNF-α and IL-1β)與肝臟組織中所含的collagen含量則是顯著的降低(p< 0.05)，並在組織病理切片的結果中發現處理組能夠有效的減緩(p <0.05)纖維的產生並且減少(p <0.05)發炎之區域。透過分子生物學之分析，OSM的護肝機制主要是藉由抑制(p <0.05)轉化生長因子(TGF-β)以及第四型類鐸受體(TLR4)相關之路徑，進而抑制(p <0.05)核因子活化B細胞κ輕鏈增強子(NFκB)之活化，最後該轉錄因子下游之發炎(COX2)與纖維化(Col1α、αSMA)相關之訊號也有顯著(p <0.05)的降低。透過免疫染色分析，OSM可以顯著減少(p <0.05)肝臟星狀細胞活化之訊號αSMA。本研究結果證實冬蟲夏草菌絲體之補充可以有效地減緩硫代乙醯胺誘導之肝損傷。

Chronic liver diseases result in persisting inflammation, progressive fibrogenesis and chronic activation of the wound healing response. This study was to exam the protective activity of compound TCM-808FB which is mycelium of Ophiocordyceps sinensis (OSM) via a wistar rat model. Although rats were induced by injecting thioacetamide (CH3C(S)NH2, TAA), oral OSM administration improved (p <0.05) the hypolipemia and lipid accumulation in livers. Meanwhile, the smaller (p <0.05) liver sizes as well as lower (p <0.05) serum alanine transaminase (AST) and asparatate transaminase (ALT) values showed its potential for relieving from the fibrosis symptom. Moreover, the results of cytokine assays, liver collagen assay and pathological section supported previous hypothesis. Besides, the OSM administration also enhanced (p <0.05) liver antioxidant capacities (GSH, TEAC, SOD, CAT and GPx) and decreased (p <0.05) lipid peroxidation (TBARS), and alleviated liver damage against TAA. As a result, we found an evidence that the protective effect of OSM against hepatic fibrosis may be via downregulations (p <0.05) of TGF-β and TLR4 pathways while OSM also decreased (p <0.05) the expression of NFκB which further decreased (p <0.05) the expressions of fibrotic and inflammatory genes (i.e., αSMA, Col1α, COX2). Therefore, OSM showed preventive effects on the development of TAA-induced hepatic fibrosis.