| 摘要: | 羥基丁酸(3-hydroxybutyrate; 3HB)在結構上有不對稱中心，因此有D-型以及L-型等兩種鏡像異構物。D-3HB為體內含量最高的酮體，可作為替代葡萄糖之能量來源。L-3HB則因其低含量及分析技術之限制而少有相關研究。D-3HB的生成路徑與脂質的代謝息息相關，且在細胞實驗中D-3HB可轉化成L-3HB。本研究使用影響脂質代謝的gentamicin(GM)觀察其對D-及L-3HB的影響，以Wistar Albino大鼠每日腹腔注射150 mg(6天)或100mg (10天)/kg/day之GM。此外，由於GM容易引起腎病變，本研究同時也探討口服給與具有腎臟保護作用之metformin(MET)、N-acetylcysteine(NAC)以及atorvastatin(ATO)時對D-及L-3HB的影響以幫助解明(D,L)-3HB之生理意義。
結果顯示在投與GM後，血清中的D-及L-3HB之濃度均顯著上升，而腎臟中則僅D-3HB具顯著上升，腎臟組織中之D-3HB/L-3HB的比值也明顯上升(5.70 ± 0.84 vs. 20.73 ± 6.18以及4.23 ± 0.66 vs. 14.40 ± 3.81; 正常組vs. GM 150 mg組以及正常組vs. GM 100 mg組, p < 0.05)。在GM+MET或GM+NAC組中D-3HB/L-3HB則顯著下降(20.73 ± 6.18 vs. 10.78 ± 1.79 vs. 6.09 ± 1.28; GM 150 mg組vs. GM+MET組vs. GM+NAC組, p < 0.05)。另一方面，GM+ATO的組別可明顯降低GM 100 mg組的D-3HB/L-3HB的數值(14.40 ± 3.81 vs. 5.47 ± 1.22; GM 100 mg組vs. GM+ATO組, p < 0.05)。
本研究顯示D-3HB/L-3HB的比值變化較濃度變化更能反映GM引起的腎損傷。
3-Hydroxybutyrate (3-HB) has one chiral center, therefore; it contains two enantiomers, D-3HB and L-3HB. D-3HB is one of the ketone bodies, which is an alternative source of energy. However, there are rarely researches associated with L-3HB because of its low content and limitation in separation technology. The pathway of D-3HB production was associated with lipid metabolism. In addition, D-3HB could convert to L-3HB in cell culture. In this study, we used Wistar Albino rat intraperitoneally injected gentamicin (GM) 150 mg (6 days) or 100 mg (10 days)/kg/day which would interfere lipid metabolism. Because GM likely to induce nephropathy, we administered three drugs orally for renal protection which were metformin (MET), N-acetylcysteine (NAC) and atorvastatin (ATO). Finally, we investigated the effect of GM, MET, NAC and ATO on D- and L-3HB for better understanding the physiological role of (D,L)-3HB.
After we administered GM, both of the concentration of D- and L-3HB were increased significantly in the rat serum. In the rat kidney, only concentration of D-3HB was increased significantly, but the ratio of D-3HB/L-3HB was also increased significantly (5.70 ± 0.84 vs. 20.73 ± 6.18 and 4.23 ± 0.66 vs. 14.40 ± 3.81; normal vs. GM 150 mg group and normal vs. GM 100 mg group, p < 0.05). In GM+MET and GM+NAC group, the ratio of D-3HB/L-3HB was decreased significantly (20.73 ± 6.18 vs. 10.78 ± 1.79 vs. 6.09 ± 1.28; GM 150 mg group vs. GM+MET group vs. GM+NAC group, p < 0.05). On the other hand, GM+ATO group could decreased the ratio of D-3HB/L-3HB significantly (14.40 ± 3.81 vs. 5.47 ± 1.22; GM 100 mg group vs. GM+ATO group, p < 0.05).
In conclusion, the changes in ratio of D-3HB/L-3HB was better to reflect the pathological conditions of GM-induced nephropathy compared with the changes in concentration. |
