胱抑素C

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血清胱抑素C
(Cystatin C)
PDB的解譯基於3gax[1].
有效结构
PDB 直系同源检索：PDBe, RCSB
标识
代号 CST3; ARMD11
扩展标识 遗传学：604312 鼠基因：102519 同源基因：78 ChEMBL: 1741304 GeneCards: CST3 Gene
RNA表达模式
更多表达数据
直系同源体
物种 人类 小鼠
Entrez 1471 13010
Ensembl ENSG00000101439 ENSMUSG00000027447
UniProt P01034 P21460
mRNA序列 NM_000099 NM_009976
蛋白序列 NP_000090 NP_034106
基因位置 Chr 20:
23.61 – 23.62 Mb		 Chr 2:
148.87 – 148.88 Mb
PubMed查询 [1] [2]


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标记。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，如阿兹海默病。在人類中，所有细胞與细胞核(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。它是一種溶酶体蛋白酶的酶抑制剂(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[编辑]

腎的功能[编辑]

参见：腎功能

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标记。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)試著調整這些變量。

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)(隨時間的推移追踪血清胱抑素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肾脏病之風險，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]在感染艾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[编辑]

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]為符合自我管裡的基因特性，已經表明半血清胱抑素C可能由基础代谢率所影響。[35]

神經系統疾病[编辑]

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，它是阿兹海默病的潛在目標。[36][37]據報導血清胱抑素C水平在阿兹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[编辑]

血清胱抑素C水平降低动脉粥样硬化(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[编辑]

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(其中的红血球和凝血因子已被去除之血液流體)的隨機樣本測定。[44]

在眾多的人口裡因性別與年齡，而有不同的參考值。

分子生物學[编辑]

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(等电点在pH9.3)。

歷史[编辑]

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裡被描述為"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[编辑]

註釋[编辑]

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外部連結[编辑]

常見澱粉樣蛋白形成的蛋白質
系統性澱粉樣變
器官局限性類澱粉樣變
取自“https://zh.100ke.info/w/index.php?title=胱抑素C&oldid=79072360”