跳转到内容

胱抑素C

维基百科，自由的百科全书
维基百科中的醫學内容仅供参考，並不能視作專業意見。如需獲取醫療幫助或意見，请咨询专业人士。詳見醫學聲明。
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]
  1. ^ Robert Kolodziejczyk, Karolina Michalska, Alejandra Hernandez-Santoyo, Maria Wahlbom, Anders Grubb, Mariusz Jaskolski. Crystal structure of human cystatin C stabilized against amyloid formation. The FEBS journal. 2010-04, 277 (7): 1726–1737 [2019-05-26]. ISSN 1742-4658. PMID 20175878. doi:10.1111/j.1742-4658.2010.07596.x. 
  2. ^ Alzforum: AlzGene. （原始内容存档于2004-12-27）. 
  3. ^ Zahran A, El-Husseini A, Shoker A. Can cystatin C replace creatinine to estimate glomerular filtration rate? A literature review. Am. J. Nephrol. 2007, 27 (2): 197–205 [2015-06-03]. PMID 17361076. doi:10.1159/000100907. （原始内容存档于2012-09-28）. 
  4. ^ 4.0 4.1 Roos JF, Doust J, Tett SE, Kirkpatrick CM. Diagnostic accuracy of cystatin C compared to serum creatinine for the estimation of renal dysfunction in adults and children--a meta-analysis. Clin. Biochem. March 2007, 40 (5–6): 383–391. PMID 17316593. doi:10.1016/j.clinbiochem.2006.10.026. 
  5. ^ King AJ, Levey AS. Dietary protein and renal function. J. Am. Soc. Nephrol. May 1993, 3 (11): 1723–37 [2015-06-03]. PMID 8329667. （原始内容存档于2023-04-07）. 
  6. ^ Dharnidharka VR, Kwon C, Stevens G. Serum cystatin C is superior to serum creatinine as a marker of kidney function: a meta-analysis. Am. J. Kidney Dis. August 2002, 40 (2): 221–226 [2015-06-03]. PMID 12148093. doi:10.1053/ajkd.2002.34487. （原始内容存档于2022-09-09）. 
  7. ^ Premaratne E, MacIsaac RJ, Finch S, Panagiotopoulos S, Ekinci E, Jerums G. Serial measurements of cystatin C are more accurate than creatinine-based methods in detecting declining renal function in type 1 diabetes. Diabetes Care. May 2008, 31 (5): 971–973 [2015-06-03]. PMID 18319326. doi:10.2337/dc07-1588. （原始内容存档于2013-04-14）. 
  8. ^ Perkins BA; Nelson RG; Ostrander BE; et al. Detection of renal function decline in patients with diabetes and normal or elevated GFR by serial measurements of serum cystatin C concentration: results of a 4-year follow-up study. J. Am. Soc. Nephrol. May 2005, 16 (5): 1404–1412. PMC 2429917 可免费查阅. PMID 15788478. doi:10.1681/ASN.2004100854. 
  9. ^ Corrao AM; Lisi G; Di Pasqua G; et al. Serum cystatin C as a reliable marker of changes in glomerular filtration rate in children with urinary tract malformations. J. Urol. January 2006, 175 (1): 303–309. PMID 16406933. doi:10.1016/S0022-5347(05)00015-7. 
  10. ^ Stevens LA; Coresh J; Schmid CH; et al. Estimating GFR using serum cystatin C alone and in combination with serum creatinine: a pooled analysis of 3,418 individuals with CKD. Am. J. Kidney Dis. March 2008, 51 (3): 395–406 [2015-06-03]. PMC 2390827 可免费查阅. PMID 18295055. doi:10.1053/j.ajkd.2007.11.018. （原始内容存档于2020-09-26）. 
  11. ^ Shlipak MG. Cystatin C as a marker of glomerular filtration rate in chronic kidney disease: influence of body composition. Nat Clin Pract Nephrol. April 2007, 3 (4): 188–189. PMID 17290239. doi:10.1038/ncpneph0404. 
  12. ^ Macdonald J; Marcora S; Jibani M; et al. GFR estimation using cystatin C is not independent of body composition. Am. J. Kidney Dis. November 2006, 48 (5): 712–719 [2015-06-03]. PMID 17059990. doi:10.1053/j.ajkd.2006.07.001. （原始内容存档于2018-09-12）. 
  13. ^ Shlipak MG; Katz R; Sarnak MJ; et al. Cystatin C and prognosis for cardiovascular and kidney outcomes in elderly persons without chronic kidney disease. Annals of Internal Medicine. August 2006, 145 (4): 237–46 [2015-06-03]. PMID 16908914. doi:10.7326/0003-4819-145-4-200608150-00003. （原始内容存档于2012-09-11）. 
  14. ^ Hermida J, Tutor JC. Serum cystatin C for the prediction of glomerular filtration rate with regard to the dose adjustment of amikacin, gentamicin, tobramycin, and vancomycin. Ther Drug Monit. June 2006, 28 (3): 326–331 [2015-06-03]. PMID 16778715. doi:10.1097/01.ftd.0000211805.89440.3d. （原始内容存档于2016-01-20）. 
  15. ^ Schück O, Teplan V, Sibová J, Stollová M. Predicting the glomerular filtration rate from serum creatinine, serum cystatin C and the Cockcroft and Gault formula with regard to drug dosage adjustment. Int J Clin Pharmacol Ther. February 2004, 42 (2): 93–7. PMID 15180169. doi:10.5414/cpp42093. 
  16. ^ Demirtaş S, Akan O, Can M, Elmali E, Akan H. Cystatin C can be affected by nonrenal factors: a preliminary study on leukemia. Clin. Biochem. February 2006, 39 (2): 115–118. PMID 16337174. doi:10.1016/j.clinbiochem.2005.10.009. 
  17. ^ Nakai K; Kikuchi M; Fujimoto K; et al. Serum levels of cystatin C in patients with malignancy. Clin. Exp. Nephrol. April 2008, 12 (2): 132–139. PMID 18317874. doi:10.1007/s10157-008-0043-8. 
  18. ^ Kos J, Stabuc B, Cimerman N, Brünner N. Serum cystatin C, a new marker of glomerular filtration rate, is increased during malignant progression. Clin. Chem. December 1998, 44 (12): 2556–7. PMID 9836733. [永久失效連結]
  19. ^ Fricker M, Wiesli P, Brändle M, Schwegler B, Schmid C. Impact of thyroid dysfunction on serum cystatin C. Kidney Int. May 2003, 63 (5): 1944–1947. PMID 12675875. doi:10.1046/j.1523-1755.2003.00925.x. 
  20. ^ Manetti L; Pardini E; Genovesi M; et al. Thyroid function differently affects serum cystatin C and creatinine concentrations. J. Endocrinol. Invest. April 2005, 28 (4): 346–9 [2015-06-03]. PMID 15966508. doi:10.1007/bf03347201. （原始内容存档于2008-06-08）. 
  21. ^ Wiesli P, Schwegler B, Spinas GA, Schmid C. Serum cystatin C is sensitive to small changes in thyroid function. Clin. Chim. Acta. December 2003, 338 (1–2): 87–90 [2015-06-03]. PMID 14637271. doi:10.1016/j.cccn.2003.07.022. （原始内容存档于2018-06-08）. 
  22. ^ Risch L, Herklotz R, Blumberg A, Huber AR. Effects of glucocorticoid immunosuppression on serum cystatin C concentrations in renal transplant patients. Clin. Chem. November 2001, 47 (11): 2055–9. PMID 11673383. [永久失效連結]
  23. ^ Cimerman N, Brguljan PM, Krasovec M, Suskovic S, Kos J. Serum cystatin C, a potent inhibitor of cysteine proteinases, is elevated in asthmatic patients. Clin. Chim. Acta. October 2000, 300 (1–2): 83–95. PMID 10958865. doi:10.1016/S0009-8981(00)00298-9. 
  24. ^ Bökenkamp A, van Wijk JA, Lentze MJ, Stoffel-Wagner B. Effect of corticosteroid therapy on serum cystatin C and beta2-microglobulin concentrations. Clin. Chem. July 2002, 48 (7): 1123–6. PMID 12089191. [永久失效連結]
  25. ^ Knight EL; Verhave JC; Spiegelman D; et al. Factors influencing serum cystatin C levels other than renal function and the impact on renal function measurement. Kidney Int. April 2004, 65 (4): 1416–1421. PMID 15086483. doi:10.1111/j.1523-1755.2004.00517.x. 
  26. ^ Odden MC; Scherzer R; Bacchetti P; et al. Cystatin C level as a marker of kidney function in human immunodeficiency virus infection: the FRAM study. Arch. Intern. Med. November 2007, 167 (20): 2213–2219 [2015-06-03]. PMC 3189482 可免费查阅. PMID 17998494. doi:10.1001/archinte.167.20.2213. （原始内容存档于2008-06-07）. 
  27. ^ Collé A; Tavera C; Prévot D; et al. Cystatin C levels in sera of patients with human immunodeficiency virus infection. A new avidin-biotin ELISA assay for its measurement. J Immunoassay. 1992, 13 (1): 47–60. PMID 1569212. doi:10.1080/15321819208019824. 
  28. ^ Jaroszewicz J, Wiercinska-Drapalo A, Lapinski TW, Prokopowicz D, Rogalska M, Parfieniuk A. Does HAART improve renal function? An association between serum cystatin C concentration, HIV viral load and HAART duration. Antivir. Ther. (Lond.). 2006, 11 (5): 641–5. PMID 16964834. 
  29. ^ Strevens H, Wide-Swensson D, Torffvit O, Grubb A. Serum cystatin C for assessment of glomerular filtration rate in pregnant and non-pregnant women. Indications of altered filtration process in pregnancy. Scand. J. Clin. Lab. Invest. 2002, 62 (2): 141–147. PMID 12004930. doi:10.1080/003655102753611771. 
  30. ^ Akbari A; Lepage N; Keely E; et al. Cystatin-C and beta trace protein as markers of renal function in pregnancy. BJOG. May 2005, 112 (5): 575–578. PMID 15842279. doi:10.1111/j.1471-0528.2004.00492.x. 
  31. ^ Sjöström P, Tidman M, Jones I. Determination of the production rate and non-renal clearance of cystatin C and estimation of the glomerular filtration rate from the serum concentration of cystatin C in humans. Scand. J. Clin. Lab. Invest. 2005, 65 (2): 111–124. PMID 16025834. doi:10.1080/00365510510013523. 
  32. ^ Tonelli M; Wiebe N; Culleton B; et al. Chronic kidney disease and mortality risk: a systematic review. J. Am. Soc. Nephrol. July 2006, 17 (7): 2034–2047. PMID 16738019. doi:10.1681/ASN.2005101085. 
  33. ^ Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N. Engl. J. Med. September 2004, 351 (13): 1296–1305. PMID 15385656. doi:10.1056/NEJMoa041031. 
  34. ^ Stevens LA, Levey AS. Chronic kidney disease in the elderly--how to assess risk. N. Engl. J. Med. May 2005, 352 (20): 2122–2124. PMID 15901867. doi:10.1056/NEJMe058035. 
  35. ^ Delanaye P, Cavalier E, Krzesinski JM. Cystatin C, renal function, and cardiovascular risk. Annals of Internal Medicine. February 2008, 148 (4): 323. PMID 18283218. doi:10.7326/0003-4819-148-4-200802190-00023. 
  36. ^ Mi W; Pawlik M; Sastre M; et al. Cystatin C inhibits amyloid-beta deposition in Alzheimer's disease mouse models. Nat. Genet. December 2007, 39 (12): 1440–1442. PMID 18026100. doi:10.1038/ng.2007.29. 
  37. ^ Kaeser SA; Herzig MC; Coomaraswamy J; et al. Cystatin C modulates cerebral beta-amyloidosis. Nat. Genet. December 2007, 39 (12): 1437–1439. PMID 18026102. doi:10.1038/ng.2007.23. 
  38. ^ Chuo LJ, Sheu WH, Pai MC, Kuo YM. Genotype and plasma concentration of cystatin C in patients with late-onset Alzheimer disease. Dement Geriatr Cogn Disord. 2007, 23 (4): 251–257 [2015-06-03]. PMID 17310123. doi:10.1159/000100021. （原始内容存档于2012-09-28）. 
  39. ^ Del Boccio P; Pieragostino D; Lugaresi A; et al. Cleavage of cystatin C is not associated with multiple sclerosis. Annals of Neurology. August 2007, 62 (2): 201–204. PMID 17006926. doi:10.1002/ana.20968. 
  40. ^ Shi GP; Sukhova GK; Grubb A; et al. Cystatin C deficiency in human atherosclerosis and aortic aneurysms. J. Clin. Invest. November 1999, 104 (9): 1191–1197. PMC 409823 可免费查阅. PMID 10545518. doi:10.1172/JCI7709. 
  41. ^ Abisi S, Burnand KG, Waltham M, Humphries J, Taylor PR, Smith A. Cysteine protease activity in the wall of abdominal aortic aneurysms. J. Vasc. Surg. December 2007, 46 (6): 1260–1266 [2015-06-03]. PMID 18155003. doi:10.1016/j.jvs.2007.08.015. （原始内容存档于2018-11-04）. 
  42. ^ Abdul-Hussien H; Soekhoe RG; Weber E; et al. Collagen degradation in the abdominal aneurysm: a conspiracy of matrix metalloproteinase and cysteine collagenases (– Scholar search). Am. J. Pathol. March 2007, 170 (3): 809–817. PMC 1864891 可免费查阅. PMID 17322367. doi:10.2353/ajpath.2007.060522.  [失效連結]
  43. ^ Gacko M, Chyczewski L, Chrostek L. Distribution, activity and concentration of cathepsin B and cystatin C in the wall of aortic aneurysm. Pol J Pathol. 1999, 50 (2): 83–6. PMID 10481531. 
  44. ^ Croda-Todd MT, Soto-Montano XJ, Hernández-Cancino PA, Juárez-Aguilar E. Adult cystatin C reference intervals determined by nephelometric immunoassay. Clin. Biochem. September 2007, 40 (13–14): 1084–1087 [2015-06-03]. PMID 17624320. doi:10.1016/j.clinbiochem.2007.05.011. （原始内容存档于2018-01-29）. 
  45. ^ 45.0 45.1 Grubb A, Löfberg H. Human gamma-trace, a basic microprotein: amino acid sequence and presence in the adenohypophysis. Proc. Natl. Acad. Sci. U.S.A. May 1982, 79 (9): 3024–3027. PMC 346341 可免费查阅. PMID 6283552. doi:10.1073/pnas.79.9.3024. 
  46. ^ Löfberg H, Grubb AO. Quantitation of gamma-trace in human biological fluids: indications for production in the central nervous system. Scand. J. Clin. Lab. Invest. November 1979, 39 (7): 619–626. PMID 119302. doi:10.3109/00365517909108866. 
  47. ^ Grubb A, Simonsen O, Sturfelt G, Truedsson L, Thysell H. Serum concentration of cystatin C, factor D and beta 2-microglobulin as a measure of glomerular filtration rate. Acta Med Scand. 1985, 218 (5): 499–503. PMID 3911736. doi:10.1111/j.0954-6820.1985.tb08880.x. 
  48. ^ Simonsen O, Grubb A, Thysell H. The blood serum concentration of cystatin C (gamma-trace) as a measure of the glomerular filtration rate. Scand. J. Clin. Lab. Invest. April 1985, 45 (2): 97–101. PMID 3923607. doi:10.3109/00365518509160980. 

外部連結

[编辑]
检索自“https://zh1.bitforum.be.eu.org/w/index.php?title=胱抑素C&oldid=82738538”