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  • 學位論文

大豆蛋白水解物對不同疾病動物模式血壓調節的作用

Effects of Soy Protein Hydrolysate on Blood Pressure in Various Animal Models

指導教授 : 陳俊榮

摘要


血管收縮素轉換?﹛?(angiotensin converting enzyme, ACE)的活性增加是 RAS 活化的重要因子之一。本研究將就三個不同的疾病動物模式,觀察攝取大豆蛋白是否可以其被消化酵素水解後的產物達到降低血壓和保護組織的功能。第一部份使用 5/6 腎切除手術作為慢性腎衰竭的動物模式,餵食實驗動物含大豆蛋白或大豆蛋白胃蛋白?﹞蘢悛?(soy protein hydrolysate, SPH)的飲食同樣具有改善因腎切除手術所造成血壓上升、血漿胰島素濃度上升、腎功能缺損及腎臟 TNF-a(tumor necrosis factor-a)濃度上升的作用。第二部分餵食實驗動物高油高果糖飲食四週以誘發代謝性症候群,接著餵食實驗動物含大豆蛋白或 SPH 的飲食八週,結果發現大豆蛋白和大豆蛋白胃蛋白?﹛水解物同樣具有降低實驗動物血壓、血糖、血脂濃度的作用,也會降低血漿、心臟和腎臟中 ACE 的活性,同時也可降低組織中 TNF-a 和 PAI-1(plasminogen activator inhibitor-1)的濃度,但對於血漿和脂肪組織中 adiponectin 的濃度皆無影響。第三部份投予實驗動物一氧化氮合成?“磻蹌? L-NAME 以誘發高血壓,在實驗動物飲食中分別添加 1%、3% 或 5% 的SPH,結果發現 5% 的 SPH 相較於控制組可降低血壓、心臟和腎臟的 ACE 活性、腎臟 PAI-1、TNF-a 濃度和 CYP 4A 的表現,同時病理組織切片也可觀察到對於心臟和腎臟組織損傷皆有改善的作用。最後我們進一步分離 SPH 中具ACE抑制活性的胜?戍レC,其中以LKNQRESY、DQMPRRF及 LVPPQESQRR三種最具ACE 抑制活性。所以我們推論大豆蛋白的攝取可能藉由其消化水解後所產生具生理活性的胜?戍レC,在體內達到抑制ACE 活性的作用,所以攝取大豆蛋白質對於腎衰竭、代謝性症候群和一氧化氮缺發的實驗動物具有降低血壓和改善組織損傷的功能。

並列摘要


Angiotensin converting enzyme plays a key physiological role in the activation of RAS (rennin-angiotensin system). We investigated the effects of pepsin-digested soy protein hydrolysate (SPH) on blood pressure and ACE activity in three different animal models in this study. In 5/6-nephrectomized rats, we found soy protein and SPH had the same renoprotective effects and decrease systolic blood pressure, plasma insulin and renal TNF-a (tumor necrosis factor-a) concentration. In rats with metabolic syndrome induced by high-fructose-high-fat diet, SPH was also as effective as soy protein in the reduction of blood pressure, plasma glucose and lipids. The soy protein and SPH group also had lower plasma, heart and renal ACE activity and tissue TNF-a and PAI-1 (plasminogen activator inhibitor-1) level than the control group. However, no difference in plasma and adipose adiponectin level was found. In the third part of study, we fed NO-deficient hypertensive rats diet containing 1%, 3% or 5% SPH. We found that the 5% SPH group had lower blood pressure, heart and renal ACE activity, renal PAI-1, TNF-a level and CYP4A expression than the control group. In pathohistological analysis, we also found that 5% SPH can protective cardiovascular and renal injuries caused by administration of NO synthase inhibitor. Furthermore, we isolated the peptides with ACE inhibitory activities in SPH, and we found that LKNQRESY, DQMPRRF and LVPPQESQRR were the three most effective peptides derived from soy protein. Therefore, we suggested that one possible mechanism of the beneficial effects of soy protein consumption on hypertension and related tissue injuries may be the ACE inhibitory peptide derived from digested soy protein.

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