新知導讀-CharXgen活性竹炭包裹在海藻酸鈉微球中作為尿毒症毒素的吸收劑以延緩腎功能惡化 by: agnes30 12 月, 2022 本篇文章導讀自: CharXgen-Activated Bamboo Charcoal Encapsulated in Sodium Alginate Microsphere as the Absorbent of Uremic Toxins to Retard Kidney Function Deterioration 以新型活性碳CharXgen餵食CKD大鼠，發現具有保護腎功能及降低血清尿毒症的潛在益處 | 摘要 硫酸吲哚酚 (IS) 和對甲酚硫酸鹽 (PCS) 是慢性腎病 (CKD) 中積累的兩種蛋白質結合尿毒症毒素。本研究的目的是評估新型活性炭 CharXgen 在 CKD 動物模型中對保護腎功能和降低血清尿毒症毒素的影響。 透過掃描電子顯微鏡 (SEM) 和 X 射線衍射儀 (XRD) 對活化前後的CharXgen進行物理特性分析，發現活化後的CharXgen 比表面積增加。 透過體外結合試驗和 CKD 動物模型評估 CharXgen 對生物化學和降低尿毒症毒素的影響。動物試驗總共分成五組，分別是正常組、假手術組(對動物進行和實驗組相同的手術處理，但並不給予實驗刺激)、CKD組、CKD + AST-120組與CKD+CharXgen組。 經掃描電子顯微鏡 (SEM) 和 X 射線衍射儀 (XRD) 分析後發現活化後的CharXgen 具有高內表面積。經體外結核試驗發現CharXgen 能夠有效吸收硫酸吲哚酚及對甲酚硫酸鹽。而在動物實驗中，CKD+CharXgen組的大鼠腎功能獲得改善，且血清中 IS 和 PCS 較低。另外，與 CKD 組相比，發現CKD+CharXgen組的大鼠成纖維細胞生長因子 23 顯著降低，這種變化在CKD + AST-120組未發現。這表明 CharXgen 是一種新型安全無毒的活性炭，具有減輕腎功能惡化和降低與蛋白質結合的尿毒症毒素的潛力。 l 簡介 患有慢性腎病 (CKD) 的患者患心血管疾病 (CVD) 的風險顯著增加，尤其是患有終末期腎病 (ESRD) 的患者。傳統的CVD高風險族群如高血壓、高血脂症和糖尿病患者不能完全解釋CVD增加的風險；而CKD患者這種非傳統的風險因子則有明確的證據支持，其中包括尿毒症毒素的積累、腎功能下降及尿毒症溶質。 尿毒症溶質包括硫酸吲哚酚 (IS) 和對甲酚硫酸鹽 (PCS)，它們是腸道菌群代謝芳香氨基酸後源自腸道的兩種蛋白質結合尿毒症毒素，會抑制內皮細胞增殖，可能導致內皮細胞功能的障礙 。而IS 的積累可能會加速腎小球硬化、氧化應激、間質纖維化及腎元減少而促進CKD的進展。IS 參與了 CKD 中 CVD 的發病機制，包括動脈粥樣硬化、外周動脈疾病、充血性心力衰竭、血栓形成和心律失常。另外，成纖維細胞生長因子 23 (FGF23) 是一種從骨分泌的磷酸尿因子，在腎臟功能衰退初期，血中FGF23的濃度即升高。FGF 23 不僅是礦物質骨紊亂的主要調節因子，而且還是導致 CKD 患者心血管發病率和死亡率的因素。因此，減少體內IS 和 PCS的濃度及降低FGF23可能可以延緩CKD的進展。 AST-120 是1991年在日本上市的口服腸道吸附劑，可透過減少 CKD 患者的炎症基因表現，有效降低血清和尿液的 IS 濃度並延緩 CKD 進展的藥物 。在美國的一項初步隨機、雙盲、安慰劑對照試驗中，AST-120 與血清 IS水平的顯著劑量依賴性降低和尿毒症相關不適的減少有關。 因此，通過 AST-120 去除 IS 不僅改善了腎功能，還降低了 CKD 患者心血管事件的風險。 但是AST-120的生產成本較高，所以應用並不廣泛。不過，還有一種從台灣竹子萃取及生產的新型活性炭 CharXgen，具有多孔結構，其安全性、腎臟保護作用以及是否可以降低血清生化指標尚不清楚。因此，作者的目的是研究 CharXgen 對 CKD 動物模型臨床參數的影響。 l 結果 圖 1.掃描電子顯微鏡 (SEM) 分析的竹炭 ( A , B ) 和 CharXgen ( C , D ) 的橫截面和縱截面。 發現Brunauer-Emmett-Teller (BET)比表面積值在竹炭活化過後顯著增加。 圖 2.比較CharXgen及AST-120 在胃腸模擬狀態下吲哚 ( A )、對甲酚 ( B ) 和磷酸鹽 ( C ) 的體外結合能力測定。 在小腸和大腸等條件下，CharXgen 對吲哚的結合親和力更高（圖 2A） 在小腸條件下，CharXgen與對甲酚的結合親和力更高；在大腸條件下，CharXgen 和 AST-120 之間的對甲酚結合親和力沒有顯著差異（圖 2B) 在口腔條件下，CharXgen對磷酸鹽的結合能力與 AST-120 相似；在胃、小腸和大腸條件下，AST-120對磷酸鹽結合能力更高，(圖 2C) 圖 3. 每組大鼠分別在餵食木炭、AST-120 或 CharXgen 後 8、16 和 24 小時的腸道狀態。 結果顯示CharXgen組腸道顏色結果與AST-120組相似，與木炭組相比沒有明顯變黑。   圖 4. 每組​​大鼠的肝功能和營養狀況。各組GPT（ A）和GOT（B）及白蛋白（C）水平無顯著差異。 GPT：谷丙轉氨酶；GOT：谷氨酸草酰乙酸轉氨酶。 CKD + AST-120組 和 CKD + CharXgen 組的肝功能，與正常組或假手術組相比沒有顯著變化（圖 4 A,B) 在血清白蛋白方面，CKD組和CKD+CharXgen組也呈現正常水平(圖4 C)   圖 5. 每組大鼠的腎功能。BUN：血尿素氮；Cr：肌酐 與 CKD 組相比，CKD + CharXgen 組的血清 BUN ( A ) 和 Cr ( B ) 水平顯著降低。 圖 6.每組大鼠的血清鈣 ( A )、磷酸鹽 ( B ) 和 FGF23 ( C ) 水平。(FGF23：成纖維細胞生長因子 23) 每組的鈣和磷酸鹽沒有顯著變化。而在FGF23中顯示CKD + CharXgen 組大鼠的 FGF23 與 CKD 組相比，水平較低。 | 結論 結果顯示 CharXgen新型活性碳具有很大的比表面積及多孔特性，且在體內安全無毒。此外，透過上述實驗發現 CharXgen 在保護大鼠腎功能和降低尿毒症有潛在益處，可能可以減輕 CKD 大鼠腎功能惡化和降低 IS 和、PCS及 FGF23 水平的潛力。不過CharXgen是否在人體腎臟中的具有保護作用還需要再進一步的研究。 l 參考文獻 Vanholder, R.; Massy, Z.; Argiles, A.; Spasovski, G.; Verbeke, F.; Lameire, N.; European Uremic Toxin Work Group. 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毒素在小腸末端(ileum)就開始產生及吸收了，還有些吃入的重金屬在胃腸就開始吸收，毒素一般 根本到不了大腸。 細粒附劑顆粒在胃腸是有選擇性的吸附，可以在胃腸就開始吸收毒素，作用比一般膠囊裝活性炭粉在大腸作用更完全。