伏馬鐮孢毒素導致高膽固醇血症的機制

Abstract

伏馬鐮孢毒素B1 (Fumonisin B1) 是一種黴菌毒素，主要是由經常汙染玉米的串珠鐮刀菌屬 (Fusarium verticillioides) 黴菌產生，許多文獻顯示，伏馬鐮孢毒素B1會造成許多動物種的高膽固醇血症，而這機制目前尚不清楚。在本研究中，主要的目標是藉由降膽固醇藥物與伏馬鐮孢毒素B1於人類肝癌細胞株 (HepG2)中之交互作用，從中找出伏馬鐮孢毒素B1導致高膽固醇血症的細胞性機制；另一方面則從豬場飼料及血液樣本找出伏馬鐮孢毒素B1與高膽固醇血症之間關聯性的野外證據。實驗結果顯示，伏馬鐮孢毒素B1會增加HepG2細胞內的膽固醇濃度，而伏馬鐮孢毒素B1也會抑制低密度脂蛋白受體 (LDL-receptor) 及輔酶A:膽固醇乙醯轉移酶 (acyl-CoA:cholesterol acyltransferase; ACAT) 的mRNA表現量，若是要以藥物控制伏馬鐮孢毒素B1導致的高膽固醇血症，Probucol可能是一種有效的藥物。另外，結果也顯示，目前台灣豬用飼料是有受到伏馬鐮孢毒素B1汙染，且檢測豬隻的血中膽固醇含量，也證實豬隻是有高膽固醇血症的情形。對於兩者之間的關連性，則需要排除其他干擾因子，才能進一步的找出關聯性的直接證據。

Fumonisin B1 (FB1) is a member of mycotoxins, produced by Fusarium verticillioides (formerly F. moniliforme), a common fungal contaminant of corn. FB1 causes hypercholesterolemia in many animal species. The mechanism of FB1-induced hypercholesterolemia is unknown. We aimed to investigate the cellular mechanism of FB1-induced hypercholesterolemia by exploring agonistic hypocholesterolemic agents in HepG2 cells, and to search for a field evidence on the link between dietary FB1 and hypercholesterolemia endemic in swine population. The results indicated that FB1 induced increases in cellular concentration of cholesterol. At the moment, FB1 inhibited expression of LDL-receptor and ACAT mRNATo control the hypercholesterolemia induced by FB1, probucol might be effective. In Taiwan, FB1 contamination was noted in pig feed. Serum cholesterol was higher than the normal range of pigs. Ruling out other factors of hypercholesterolemia might be helpful to conclude a direct link between dietary FB1 and hypercholesterolemia.