探討機能性雞肝水解物對於Streptozotocin-Nicotinamide誘導小鼠認知障礙之改善功效

Abstract

糖尿病為常見之代謝性疾病之一，主要為胰島素缺乏或是產生阻抗導致體內血糖失衡，而高血糖也容易造成體內糖化終端產物(advanced glycation end products, AGEs)的堆積進而提升氧化壓力，造成認知行為障礙。本研究即探討富含支鏈胺基酸之雞肝水解物(chicken liver hydrolysates, CLHs)有無調降血糖、氧化壓力以及認知障礙的功效。實驗以注射鏈脲佐菌素(streptozotocin, STZ)與nicotinamide誘導ICR小鼠高血糖並補充低、中、高劑量(409.46, 818.92, and 1223.38 mg/kg BW) CLHs，而由動物實驗結果顯示：補充中、高劑量CLHs後可顯著提升腦與血清之抗氧化能力(p<0.05)。在血糖方面，補充CLHs的高血糖組別血糖值在第三、六、九週顯著低於無補充高血糖組別(p<0.05)，葡萄糖耐受性試驗血糖之曲線下面積則顯著減少(p<0.05)；而從胰島素敏感性來看，補充CLHs組別胰島素與胰島素阻抗程度(homeostatic model assessment for insulin resistance, HOMA- IR)顯著低於無補充高血糖組別(p<0.05)。在行為學實驗上：CLHs可縮短小鼠在水迷宮中找到逃脫平台的時間(p<0.05)，並滯留於原平台區域時間顯著更長，穿越次數也更多(p<0.05)；而在Y迷宮中的探索能力則顯著改善(p<0.05)。從腦部組織切片結果觀察：H&E染色中可看出高血糖組別之神經細胞呈現萎縮的趨勢，使得蘇木精顏色的比例更多，在IHC染色中補充中、高劑量CLHs的組別則有減少β-amyloid堆積的現象(p<0.05)。而補充CLHs後，AGEs堆積程度有減少趨勢，使凋亡相關蛋白質(receptor for advanced glycation end products, RAGE; c-Jun N-terminal kinase, JNK; Caspase 3)表現量減少(p<0.05)。綜觀上述結果：CLHs補充具有緩解血糖上升與氧化壓力，減緩腦細胞之凋亡程度，進而改善探索能力與空間記憶的效果。

Diabetes mellitus (DM) is a common metabolic syndrome, which causes hyperglycemia due to insufficient insulin or insulin resistance. The excessive blood glucose produces advanced glycation end products (AGEs) and then induces oxidative stress, thus leading cognitive dysfunction. This study was to investigate the protective effects of chicken liver hydrolysates (CLHs) in low, medium, and high doses (409.46, 818.92, and 1223.38 mg/kg BW) on hyperglycemia, oxidative stress, and cognitive dysfunction in streptozotocin (STZ)-nicotinamide induced hyperglycemic ICR mice. Current results showed that medium and high doses of CLHs resulted in higher (p<0.05) antioxidant capacities in sera and brains of STZ induced hyperglycemic mice. In addition, CLH supplementation reduced (p<0.05) the level of blood glucose of STZ induced mice in 3, 6, and 9 weeks of experiment. CLH supplemented group also had lower (p<0.05) blood glucose area under the curve (AUC) and homeostatic model assessment for insulin resistance (HOMA-IR). CLH supplementation also reduced (p<0.05) the escape latencies in the reference memory test, extend (p<0.05) the spent time on target zone in the probe test, and enhance (p<0.05) alternation behavior in Y-maze. Meanwhile, CLH supplemented groups had less contracted neuron bodies in the hippocampus, which can be stained by hematoxylin in hematoxylin and eosin (H&E) stainings, and showed lower (p<0.05) β-amyloid (Aβ) deposits in immunochemical stainings. Although there was only a tendency toward less AGEs accumulation by CLH supplementation, the expression of apoptosis related protein, such as receptor for advanced glycation end products (RAGE), c-Jun N-terminal kinase (JNK), and Caspase 3 were decreased (p<0.05) in STZ induced mice co-treated with CLHs. To sum up, our patented CLHs have abilities to reduce cognitive dysfunction via inhibiting hyperglycemia, oxidative stress, and apoptosis in the STZ induced hyperglycemic mice.