胱抑素C
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胱抑素C(cystatin C、cystatin 3、gamma trace、血清胱抑素C、半胱氨酸蛋白酶抑制劑、胱蛋白、後γ-球蛋白,或神經內分泌基本多肽),[2]是由CST3基因編碼的一種蛋白質,其分子量小(13000)由體內有核細胞恆定產生,能自由通過(濾過)腎小球,且腎小管上皮細胞不分泌亦不重吸收,主要用作腎功能的生物標記。最近,已經研究了其在預測新發或惡化的心血管疾病的作用。它也似乎涉及類澱粉蛋白(一種特定類型的蛋白沉積)的腦功能障礙,如阿茲海默病。在人類中,所有細胞與細胞核(含DNA的細胞芯)產生具有120個氨基酸肽之血清胱抑素C。它幾乎存在於所有的組織及體液中。它是一種溶酶體蛋白酶的酶抑制劑(來自於分解蛋白質的特定細胞亞單位的一種酶),及可能是一種最重要的半胱氨酸蛋白酶(Cysteine protease)細胞外的(Extracellular)的抑製劑(經由的特定類型蛋白質降解酶、它可以防止細胞外蛋白質分解)。血清胱抑素C屬於基因家族2型胱抑素(Cystatin)。
醫學上的作用
腎的功能
腎小球濾過率(GFR)、腎臟健康標記物,最好是經由注入如菊粉、放射性同位素如51Cr-EDTA、125I-碘酞酸鹽、99mTc-DTPA(pentetic acid)或造影劑如碘海醇(iohexol)等化合物測定,但這些技術有些複雜、昂貴、耗時且具有潛在的副作用。[3][4]肌酸酐是腎功能最廣泛使用的生物標記。這在檢測輕度腎功能損害是不準確的,並且檢測水平會因肌肉質量及蛋白質的攝入量而有所不同。[5]公式如"克羅夫特-高爾特公式"及"腎病飲食改進(MDRD)公式"(參見腎功能)試着調整這些變量。
半胱氨酸蛋白酶抑製劑C具有低分子量(約13.3千道爾頓),它是由血流在經由腎臟腎小球濾過而移除出來。如果腎功能和腎小球濾過率下降,胱抑素C血液水平升高。比起血清肌酸酐水平、血清胱抑素C的血清水平是腎功能(如腎小球濾過率、以GFR表示)的一個更精確的測試。[4][6]這一發現主要是基於橫斷面研究(Cross-sectional study)(在一單一的時間點)。縱向研究(Longitudinal study)(隨時間的推移追蹤血清胱抑素C)比較少;一些研究表明為有前景的成果。[7][8][9]相比於肌酸酐、血清胱抑素C的水平較少依賴年齡、性別、種族及肌肉質量等參數。單獨的血清胱抑素C的測量還沒有被證明優於腎功能的調整估計公式。[10]相對於之前的聲稱,血清胱抑素C已被發現受到身體組成的影響。[11][12]據認為,胱抑素C可以預測發展中的慢性腎臟病之風險,從而標示出"臨床"腎功能不全的狀態。[13]
研究還調查了胱抑素C作為腎功能藥物劑量調整的標誌。[14][15]
血清胱抑素C水平據報導會因患者致癌、[16][17][18](甚至輕微的)甲狀腺功能障礙[19][20][21]及一些糖皮質激素的療法[22][23]但並非所有的情況[24]而有所改變。其它的報告已經發現,其水平受到吸煙及C反應蛋白水平的影響。[25]在感染愛滋病毒時水平似乎在增加,這可能會或可能不會反映實際的腎功能不全。[26][27][28]在懷孕期間胱抑素C監測GFR的作用仍存在着爭議。[29][30]如肌酸酐一樣,胱抑素C的消除經由除使腎臟增加GFR的惡化外的路徑。[31]
死亡及心血管疾病
腎功能不全會增加死亡和心血管疾病的風險。[32][33] 因為血清胱抑素C長期預後的結果已經出現可能比預期的GFR更強,已經假設血清胱抑素C也可能連接到獨立腎功能的一種死亡率方式。[34]為符合自我管裏的基因特性,已經表明半血清胱抑素C可能由基礎代謝率所影響。[35]
神經系統疾病
這條件繼承了顯性(Dominance (genetics))的方式。
因為血清胱抑素C還結合β澱粉樣蛋白(Amyloid beta)並降低其聚集及沉積,它是阿茲海默病的潛在目標。[36][37]據報導血清胱抑素C水平在阿茲海默病病患上顯得較高。[38]
血清胱抑素C在多發性硬化症(Multiple sclerosis (MS))及其它脫髓鞘症(demyelinating disease)(其病徵在髓鞘神經鞘的病損)的作用仍有爭議。[39]
其他功用
血清胱抑素C水平降低動脈粥樣硬化(所謂的動脈硬化)及主動脈的動脈瘤(aneurysm)(囊狀膨出)病變。[40][41][42][43]
實驗室測試
血清胱抑素C可使用免疫測定(immunoassay)法、如濁度計(nephelometer)或顆粒增強比濁法(turbidimetry)進行血清(其中的紅血球和凝血因子已被去除之血液流體)的隨機樣本測定。[44]
在眾多的人口裏因性別與年齡,而有不同的參考值。
分子生物學
血清胱抑素C超級家族包括包含多個胱抑素樣序列的蛋白質。
血清胱抑素C為一種非醣基化,鹼性蛋白質(等電點在pH9.3)。
歷史
血清胱抑素C最早於1961年在腎功能衰竭患者的尿液及腦脊液裏被描述為"γ-軌跡"連同其它的軌跡(例如β-軌跡)作為一種微量蛋白。[45]格拉布(Grubb)與洛夫柏格(Löfberg)首次報導其氨基酸序列。[45]他們注意到晚期腎功能衰竭病患增加。[46]1985年由格拉布及其同事第一次提出作為腎小球濾過率的量測方法。[47][48]
根據2012年7月5日新英格蘭醫學雜誌的一篇研究報告指出利用血清肌酸酐和胱抑素C被發現可以非常有效精確地反映GFR值。
參見
註釋
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外部連結
- Cystatin: a protein that flips out! QUite Interesting PDB Structure article at PDBe (頁面存檔備份,存於互聯網檔案館)
- The MEROPS online database for peptidases and their inhibitors: I25.004 (頁面存檔備份,存於互聯網檔案館)
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