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胱抑素C

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血清胱抑素C
(Cystatin C)
PDB的解译基于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剂、胱蛋白、后γ-球蛋白，或神经内分泌基本多肽)，[2]是由CST3基因编码的一种蛋白质，其分子量小(13000)由体内有核细胞恒定产生，能自由通过(滤过)肾小球，且肾小管上皮细胞不分泌亦不重吸收，主要用作肾功能的生物标记。最近，已经研究了其在预测新发或恶化的心血管疾病的作用。它也似乎涉及类淀粉蛋白(一种特定类型的蛋白沉积)的脑功能障碍，如阿兹海默病。在人类中，所有细胞与细胞核(含DNA的细胞芯)产生具有120个氨基酸肽之血清胱抑素C。它几乎存在于所有的组织及体液中。它是一种溶酶体蛋白酶的酶抑制剂(来自于分解蛋白质的特定细胞亚单位的一种酶)，及可能是一种最重要的半胱氨酸蛋白酶(Cysteine protease)细胞外的(Extracellular)的抑制剂(经由的特定类型蛋白质降解酶、它可以防止细胞外蛋白质分解)。血清胱抑素C属于基因家族2型胱抑素(Cystatin)。

医学上的作用

肾的功能

参见：肾功能

肾小球滤过率(GFR)、肾脏健康标记物，最好是经由注入如菊粉、放射性同位素如51Cr-EDTA、125I-碘酞酸盐、99mTc-DTPA(pentetic acid)或造影剂如碘海醇(iohexol)等化合物测定，但这些技术有些复杂、昂贵、耗时且具有潜在的副作用。[3][4]肌酸酐是肾功能最广泛使用的生物标记。这在检测轻度肾功能损害是不准确的，并且检测水平会因肌肉质量及蛋白质的摄入量而有所不同。[5]公式如"克罗夫特-高尔特公式"及"肾病饮食改进(MDRD)公式"(参见肾功能)试着调整这些变量。

半胱氨酸蛋白酶抑制剂C具有低分子量(约13.3千道尔顿)，它是由血流在经由肾脏肾小球滤过而移除出来。如果肾功能和肾小球滤过率下降，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的血清水平是肾功能(如肾小球滤过率、以GFR表示)的一个更精确的测试。[4][6]这一发现主要是基于横断面研究(Cross-sectional study)(在一单一的时间点)。纵向研究(Longitudinal study)(随时间的推移追踪血清胱抑素C)比较少；一些研究表明为有前景的成果。[7][8][9]相比于肌酸酐、血清胱抑素C的水平较少依赖年龄、性别、种族及肌肉质量等参数。单独的血清胱抑素C的测量还没有被证明优于肾功能的调整估计公式。[10]相对于之前的声称，血清胱抑素C已被发现受到身体组成的影响。[11][12]据认为，胱抑素C可以预测发展中的慢性肾脏病之风险，从而标示出"临床"肾功能不全的状态。[13]

研究还调查了胱抑素C作为肾功能药物剂量调整的标志。[14][15]

血清胱抑素C水平据报导会因患者致癌、[16][17][18](甚至轻微的)甲状腺功能障碍[19][20][21]及一些糖皮质激素的疗法[22][23]但并非所有的情况[24]而有所改变。其它的报告已经发现，其水平受到吸烟及C反应蛋白水平的影响。[25]在感染艾滋病毒时水平似乎在增加，这可能会或可能不会反映实际的肾功能不全。[26][27][28]在怀孕期间胱抑素C监测GFR的作用仍存在着争议。[29][30]如肌酸酐一样，胱抑素C的消除经由除使肾脏增加GFR的恶化外的路径。[31]

死亡及心血管疾病

肾功能不全会增加死亡和心血管疾病的风险。[32][33] 因为血清胱抑素C长期预后的结果已经出现可能比预期的GFR更强，已经假设血清胱抑素C也可能连接到独立肾功能的一种死亡率方式。[34]为符合自我管里的基因特性，已经表明半血清胱抑素C可能由基础代谢率所影响。[35]

神经系统疾病

这条件继承了显性(Dominance (genetics))的方式。

因为血清胱抑素C还结合β淀粉样蛋白(Amyloid beta)并降低其聚集及沉积，它是阿兹海默病的潜在目标。[36][37]据报导血清胱抑素C水平在阿兹海默病病患上显得较高。[38]

血清胱抑素C在多发性硬化症(Multiple sclerosis (MS))及其它脱髓鞘症(demyelinating disease)(其病征在髓鞘神经鞘的病损)的作用仍有争议。[39]

其他功用

血清胱抑素C水平降低动脉粥样硬化(所谓的动脉硬化)及主动脉的动脉瘤(aneurysm)(囊状膨出)病变。[40][41][42][43]

实验室测试

血清胱抑素C可使用免疫测定(immunoassay)法、如浊度计(nephelometer)或颗粒增强比浊法(turbidimetry)进行血清(其中的红血球和凝血因子已被去除之血液流体)的随机样本测定。[44]

在众多的人口里因性别与年龄，而有不同的参考值。

分子生物学

血清胱抑素C超级家族包括包含多个胱抑素样序列的蛋白质。

血清胱抑素C为一种非糖基化，碱性蛋白质(等电点在pH9.3)。

历史

血清胱抑素C最早于1961年在肾功能衰竭患者的尿液及脑脊液里被描述为"γ-轨迹"连同其它的轨迹(例如β-轨迹)作为一种微量蛋白。[45]格拉布(Grubb)与洛夫柏格(Löfberg)首次报导其氨基酸序列。[45]他们注意到晚期肾功能衰竭病患增加。[46]1985年由格拉布及其同事第一次提出作为肾小球滤过率的量测方法。[47][48]

根据2012年7月5日新英格兰医学杂志的一篇研究报告指出利用血清肌酸酐和胱抑素C被发现可以非常有效精确地反映GFR值。

参见

注释

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外部链接

检索自“https://zh.wikipedia.org/w/index.php?title=胱抑素C&oldid=82738538”