消渴草減輕高脂飼料及Streptozotocin誘導第二型糖尿病大鼠主動脈損傷之研究

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2015

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第二型糖尿病 (type 2 diabetes mellitus, Type 2 DM)因胰島素阻抗 (insulin resistance) 造成高胰島素血症 (hyperinsulinemia),而高胰島素血症與高葡萄糖血症 (hyperglycemia)為糖尿病血管病變的重要影響因子。糖尿病血管病變包含大血管 (macrovascular) 及小血管 (microvascular) 病變,其中大血管病變常見為動脈粥狀硬化症,易造成患者心臟疾病的發生並導致死亡。研究指出,消渴草 (Ruellia tuberosa L.) 具有抗氧化、抗發炎、抗癌等生理活性,亦可調節糖尿病大鼠之血脂平衡。本研究首先以小鼠肌肉C2C12細胞進行細胞試驗,結果顯示,在測試濃度(25、50、100、200、400及800μg/ml)下消渴草水及乙醇萃取物皆不具有細胞毒性;接著建立以TNF-α誘導胰島素阻抗細胞模式,發現在TNF-α 10ng/ml的濃度下,可有效誘導C2C12細胞產生胰島素阻抗;之後再以此細胞模式篩選具改善胰島素阻抗潛力之消渴草萃取物,結果顯示,不論是水或乙醇之消渴草萃取物,在濃度25μg/ml下即具有改善胰島素阻抗之C2C12細胞葡萄糖攝入之能力(p<0.05)。動物試驗結果顯示,每日餵食消渴草水及乙醇萃取物(劑量100與400mg/kg BW/day) 4週後可顯著改善高脂飼料及STZ誘導第二型糖尿病大鼠葡萄糖耐受能力。血液分析的結果顯示,消渴草萃取物可調節血脂及降低發炎反應相關因子,如:TNF-α, IL-6, VCAM-1, ICAM-1的含量;組織分析結果顯示,消渴草萃取物可增加抗氧化酵素SOD的活性及catalase的活性,並且降低發炎反應相關黏附因子MCP-1, VCAM-1的含量(p<0.05)。此外,消渴草萃取物可降低血管傷害相關因子,如:eNOS, ET-1, TF, vWF的含量(p<0.05),使其恢復至正常值。 由上述結果推測,消渴草可以透過改善胰島素阻抗、發炎反應、氧化壓力等作用,而達到減輕高脂飼料及STZ誘導第二型糖尿病大鼠主動脈損傷之效果。
The diabetes mellitus patients are mainly Type 2 DM, which is characterized by hyperinsulinemia resulted from insulin resistance. Researches indicated that hyperinsulinemia and hyperglycemia are important factors in diabetic vascular disease, including macrovascular and microvascular disease. Ruellia tuberosa L. (RTL) was used as folklore medicine for diabetes in Asia as well as Taiwan. RTL was previously reported to exhibit anti-oxidant, anti-inflammatory and anti-cancer abilities. The mouse muscle myotube C2C12 cells were treated with 10ng/mL TNF-α to induce insulin resistance. These cells were subsequently co-incubated with water or ethanol extract from RTL. The uptake of 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-d-glucose (2-NBDG) in insulin-resistant C2C12 cells was used as a platform for screening extracts from RTL with the anti-hyperglycemic potential. The protective effect of RTL extract on aorta damage in high-fat diet plus streptozotocin induced T2DM rats was further investigated. The results show that both water and ethanol extracts from RTL (25μg/ml) significantly improves the glucose uptake in insulin-resistant C2C12 cells (p< 0.05). Both water and ethanol extracts from RTL (100 and 400mg/kg BW/day) significantly decreases plasma glucose level, decreases the concents of serum TNF-α, IL-6 and VCAM-1. The enzyme-linked immunosorbent analysis suggested that RTL decreases the contents of MCP-1, VCAM-1 and recovers the contents of eNOS, ET-1, TF and vWF in the aortas of diabetic rats. The above observations suggested that RTL may alleviate the aorta damage via improving insulin resistance, inflammation and oxidative stress in high-fat diet plus STZ induced T2DM rats.

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第二型糖尿病, 消渴草, 主動脈損傷, Type 2 diabetes mellitus, Ruellia tuberosa L., Aorta damage

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