穀胱甘肽或/和N－乙醯半胱胺酸的補充對慢性腎功能損傷小鼠的氧化壓力及抗氧化能力的影響

Effects of glutathione or/and N-acetylcysteine supplementation on oxidative stress and antioxidant capacities in mice with chronic kidney injury

陸晴(Qing Lu 陸晴)

指導教授 ： 黃怡嘉

中山醫學大學/健康管理學院/營養學系/碩士(2019年)

https://doi.org/10.6834/CSMU201900121

摘要

穀胱甘肽 (glutathione, GSH) 及其相關抗氧化酵素是生物體內主要的抗氧化防禦系統。半胱胺酸為生成 GSH 的前驅物質，可有效提升體內抗氧化能力。當腎功能逐漸損傷過程中會增加其氧化壓力，補充 GSH 或 N－乙醯半胱胺酸 (N-acetylcysteine, NAC－半胱胺酸的補充劑型) 可能有助於增加腎臟抗氧化能力，但合併 GSH 及 NAC 是否具有更好的抗氧化效果則未被研究。本研究目的為探討單獨或合併給予 GSH 及 NAC 補充後對腎損傷小鼠的氧化壓力及抗氧化能力之影響。C57BL/6J 小鼠隨機分成 5 組，分別為：對照組 (給予 0.9 % 生理食鹽水，n＝10)、腎損傷組 (以 celecoxib 誘發腎損傷，n＝10)、GSH 組 (celecoxib＋GSH，n＝8)、NAC 組 (celecoxib＋NAC，n＝10) 及 GSH＋NAC 組 (celecoxib＋GSH＋NAC，n＝8)，於介入第 8 週結束時犧牲。結果顯示 300 mg/kg BW 的 celecoxib 會造成小鼠輕微腎損傷及氧化－抗氧化平衡改變，且氧化壓力指標與 GSH (rs＝0.52, p < 0.001) 和氧化型 GSH (rs＝0.48, p < 0.001) 濃度及 GSH 還原酶活性 (rs＝0.40, p < 0.01) 呈顯著正相關。給予 GSH 或 NAC 的補充後相較於腎損傷組並無顯著降低氧化壓力，但 GSH 的補充能增加還原型和氧化型 GSH 比值及 GSH 還原酶活性。給予 GSH 合併 NAC 補充相較單獨補充時無法更顯著增加 GSH 濃度及相關抗氧化酵素活性。結論為給予些微腎損傷小鼠補充 GSH 後會促進抗氧化防禦能力，但單獨 NAC 及合併 GSH 的補充則無顯著增加抗氧化能力及降低氧化壓力的效果。

關鍵字

穀胱甘肽N－乙醯半胱胺酸 ； 氧化壓力 ； 慢性腎損傷

並列摘要

Glutathione (GSH) and GSH-related antioxidant enzymes are the main antioxidant defense system in organism. Cysteine is a precursor of GSH synthesis, and can effectively enhance antioxidant capacities. Oxidative stress is increased when kidney function is gradually damaged. Although the supplementation of GSH or N-acetylcysteine (NAC, a supplemented form of cysteine) may increase antioxidant capacities of kidney, the effect of the combination of GSH and NAC on antioxidant capacities is unknown. The purpose of this study was to investigate the effects of GSH or/and NAC supplementation on oxidative stress and antioxidant capacities in mice with chronic kidney injury. C57BL/6J mice were randomized into 5 groups: control group (0.9% normal saline, n = 10), celecoxib group (chronic kidney injury induced by celecoxib, n=10), GSH group (GSH + celecoxib, n = 8), NAC group (NAC + celecoxib, n = 10) and GSH + NAC group (celecoxib + GSH + NAC, n = 8). Mice were sacrificed at the end of the 8th week. Results indicated that300 mg/kg body weight celecoxib could induce mild chronic kidney injury and the imbalance of oxidative stress and antioxidant capacities. The indicator of oxidative stress significantly positively correlated with levels of GSH (rs = 0.52, p < 0.001), oxidized glutathione (rs = 0.48, p < 0.001) and activity of GSH reductase (rs = 0.40, p < 0.01) in the celecoxib group. There was no significant reduction in oxidative stress in the GSH and NAC groups when compared with the celecoxib group. The ratio of GSH and oxidized GSH and GSH reductase activity increased in the GSH group. There were no significant increases in GSH concentration and related antioxidant enzymes activities in the GSH + NAC group when compared with either GSH or NAC groups. In conclusion, the supplementation of GSH could increase antioxidant capacities in mice with mild kidney injury. However, neither NAC nor GSH plus NAC supplementation had effects on antioxidant capacities and oxidative stress.

並列關鍵字

glutathione ； N-acetylcysteine ； oxidative stress ； chronic kidney injury

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