高等学校化学学报 ›› 2021, Vol. 42 ›› Issue (6): 1952.doi: 10.7503/cjcu20200879
收稿日期:
2020-12-21
出版日期:
2021-06-10
发布日期:
2021-06-08
通讯作者:
彭新艳
E-mail:pengxy1055@163.com
基金资助:
Received:
2020-12-21
Online:
2021-06-10
Published:
2021-06-08
Contact:
PENG Xinyan
E-mail:pengxy1055@163.com
Supported by:
摘要:
蛋白结合类毒素(PBUT)在尿毒症并发症的发生发展中起着重要作用, 现有血液净化模式对其清除效果较差, 开发用于高效清除尿毒症患者体内PBUT的血液灌流吸附材料已成为迫切的临床需求. 本文首先采用悬浮聚合法制备了咪唑基改性低交联聚苯乙烯微球P(St-DVB-VMZ); 然后通过小分子外交联剂的一步法傅克烷基化后交联反应, 制备出血液灌流用含咪唑基超高交联聚苯乙烯多孔树脂吸附剂HCP(St-DVB-VMZ). 利用傅里叶变换红外光谱(FTIR)、 X射线光电子能谱(XPS)、 扫描电子显微镜(SEM)及N2吸附-脱附分析等表征了吸附树脂的化学结构和微观孔结构. 结果表明, HCP(St-DVB-VMZ)具有丰富的孔结构, 比表面积达到709 m2/g. 尿毒症毒素吸附实验结果表明, HCP(St-DVB-VMZ)对蛋白结合类毒素[对硫酸吲哚酚(IS)、 对甲酚硫酸盐(PCS)和吲哚乙酸(IAA)]和中大分子毒素[甲状旁腺激素(PTH)、 β2-微球蛋白(β2M)及白细胞介素6(IL-6)]均具有优异的吸附性能并展示出较好的血液相容性, 有望实现全血灌流临床应用.
中图分类号:
TrendMD:
刘云鸿, 彭新艳. 新型蛋白结合类毒素血液灌流吸附剂的制备及吸附性能. 高等学校化学学报, 2021, 42(6): 1952.
LIU Yunhong, PENG Xinyan. Preparation and Property of A Novel Hemoperfusion Adsorbent For Protein-bound Uremic Toxins. Chem. J. Chinese Universities, 2021, 42(6): 1952.
Fig.2 Optical microscopy micrographs(A, D) and SEM images(B, C, E, F) of P(St?DVB?VMZ)(A—C) and HCP(St?DVB?VMZ)(D—F)(B, E) The surface zone; (C, F) the cross?section zone. Insets of (A) and (D) are their SEM cross-section morphologies after mechanical compression.
Sample | SBET/(m2·g-1) | Smicro/(m2·g-1) | Vp/(cm3·g-1) | Vmicro/(cm3·g-1) | Average pore size/nm |
---|---|---|---|---|---|
P(St?DVB?VMZ) | 80 | 9 | 0.19 | 0.0037 | 74.84 |
HCP(St?DVB?VMZ) | 709 | 481 | 0.62 | 0.2000 | 4.31 |
Table 1 Textural properties of P(St-DVB-VMZ) and HCP(St-DVB-VMZ)
Sample | SBET/(m2·g-1) | Smicro/(m2·g-1) | Vp/(cm3·g-1) | Vmicro/(cm3·g-1) | Average pore size/nm |
---|---|---|---|---|---|
P(St?DVB?VMZ) | 80 | 9 | 0.19 | 0.0037 | 74.84 |
HCP(St?DVB?VMZ) | 709 | 481 | 0.62 | 0.2000 | 4.31 |
Fig.5 Survey XPS spectra of P(St?DVB?VMZ) and HCP(St?DVB?VMZ)(A), O1sXPS spectra for HCP(St?DVB?VMZ)(B) and N1s XPS spectra for P(St?DVB?VMZ)(C) and HCP(St?DVB?VMZ)(D)
Fig.6 Adsorption rates of HA130 resin, P(St?DVB?VM2Z) and HCP(St?DVB?VMZ) for IS(A), PCS(B) and IAA(C) in BSA solutionThe initial concentrations of IS, PCS and IAA were 25.0, 25.0 and 5 mg/L, respectively.
Fig.7 Adsorption rates of HA?130 and HCPCST?DVB?VMZ for PBUT toxins(A) and large middle molecule uraemic toxins(B) in the human plasma with the treatment time of 2.0 hThe initial concentrations of IS, PCS, IAA, PTH, β2M and IL-6 were 25.0 mg/L, 25.0 mg/L, 5 mg/L, 180 pmol/L, 5 mg/L and 300 pg/mL, respectively. All the experiments were carried out twice and the mean values were used in the analysis of data.
Fig.8 Adsorption isotherms of HCP(St?DVB?VMZ) for PBUT(A) Non-linear Langmuir; (B) linear Langmuir; (C) non-linear Freundlich; (D) linear Freundlich model fitting plots.
PBUT | Fitting method | Langmuir | Freundlich | ||||
---|---|---|---|---|---|---|---|
qm/(mg·g-1) | KL/(L·mg-1) | R2 | KF/(mg·g-1)(L·mg-1)1/n | 1/n | R2 | ||
PCS | Linear | 73.86 | 0.01149 | 0.9940 | 6.858 | 0.3543 | 0.9680 |
Non?linear | 75.78 | 0.01061 | 0.9931 | 9.888 | 0.2924 | 0.8983 | |
IAA | Linear | 122.70 | 0.01531 | 0.9903 | 10.045 | 0.3792 | 0.9617 |
Non?linear | 137.92 | 0.00925 | 0.9868 | 14.926 | 0.3145 | 0.9620 |
Table 2 Adsorption isotherm parameters of HCP(St-DVB-VMZ) towards PBUT
PBUT | Fitting method | Langmuir | Freundlich | ||||
---|---|---|---|---|---|---|---|
qm/(mg·g-1) | KL/(L·mg-1) | R2 | KF/(mg·g-1)(L·mg-1)1/n | 1/n | R2 | ||
PCS | Linear | 73.86 | 0.01149 | 0.9940 | 6.858 | 0.3543 | 0.9680 |
Non?linear | 75.78 | 0.01061 | 0.9931 | 9.888 | 0.2924 | 0.8983 | |
IAA | Linear | 122.70 | 0.01531 | 0.9903 | 10.045 | 0.3792 | 0.9617 |
Non?linear | 137.92 | 0.00925 | 0.9868 | 14.926 | 0.3145 | 0.9620 |
Fig.9 Adsorption kinetics of HCP(St?DVB?VMZ) for PBUT(A) PBUT uptake versus time in PBS solution; (B) adsorption kinetic of pseudo-1st-order; (C) pseudo-2nd-order fitting plots for the PBUT adsorption. The initial concentration of PCS and IAA were both 100 mg/L.
PBUT | qe,exp/(mg·g-1) | Pseudo?1st?order | Pseudo?2nd?order | ||||
---|---|---|---|---|---|---|---|
qe,cal,1/(mg·g-1) | k1/min-1 | R2 | qe,cal,2/(mg·g-1) | k2/( g-1·mg-1·min-1) | R2 | ||
PCS | 21.56 | 3.69 | 0.0045 | 0.9404 | 21.35 | 0.0037 | 0.9993 |
IAA | 27.20 | 12.12 | 0.0056 | 0.9541 | 26.75 | 0.0012 | 0.9943 |
Table 3 Adsorption kinetic parameters of HCP(St-DVB-VMZ) towards PBUT
PBUT | qe,exp/(mg·g-1) | Pseudo?1st?order | Pseudo?2nd?order | ||||
---|---|---|---|---|---|---|---|
qe,cal,1/(mg·g-1) | k1/min-1 | R2 | qe,cal,2/(mg·g-1) | k2/( g-1·mg-1·min-1) | R2 | ||
PCS | 21.56 | 3.69 | 0.0045 | 0.9404 | 21.35 | 0.0037 | 0.9993 |
IAA | 27.20 | 12.12 | 0.0056 | 0.9541 | 26.75 | 0.0012 | 0.9943 |
Fig.10 Calculated adsorption rate of total protein(A) and albumin(B) from human plasma on different adsorbentsAdsorption time: 2 h. All values are expressed as mean±SD(n=3).
Fig.12 Recalcification time of the controls and adsorbents(+): Hydrophilic glass beads; (-): blank tube. Data are expressed as mean±SD of three independent measurements.
1 | Hideki F., Shunsuke G., Masafumi F., Toxins, 2018, 10(5), 202 |
2 | Shi Y. Y., Ding F., Shanghai Medical & Pharmaceutical Journal, 2018, 39(9), 12—16(史媛媛, 丁峰. 上海医药, 2018, 39(9), 12—16) |
3 | Veldeman L., Vanmassenhove J., van Biesen W., Massy Z. A., Liabeuf S., Glorieux G., Vanholder R., International Urology and Nephrology, 2019, 51(2), 293—302 |
4 | Krieter D., Kerwagen S., Rüth M., Lemke H., Wanner C., Toxins, 2019, 11(1), 47 |
5 | Duranton F., Cohen G., De Smet R., Rodriguez M., Jankowski J., Vanholder R., Argiles A., J. Am. Soc. Nephrol., 2012, 23(7), 1258—1270 |
6 | Guo J., Lu L., Hua Y., Huang K., Wang I., Huang L., Fu Q., Chen A., Chan P., Fan H., American Journal of Physiology⁃heart and Circulatory Physiology, 2017, 313(1), H1—H13 |
7 | Brunet P., Dou L., Cerini C., Berland Y., Advances in Renal Replacement Therapy, 2003, 10(4), 310—320 |
8 | Vaibhav M., Stephan T., Xia T., Doris H. F., Peter K., Scientific Reports, 2019, 9(1), 1—13 |
9 | Snauwaert E., van Biesen W., Raes A., Glorieux G., Vande W. J., Roels S., Vanholder R., Askiti V., Azukaitis K., Bayazit A., Nephrology Dialysis Transplantation, 2020, 35(4), 648—656 |
10 | Ou Z. Q., Li X. L., Zhang H., Li H. X., Lun L. D., Chinese Journal of Blood Purification, 2018, 17(4), 229—233(欧志强, 李新伦, 张宏, 李红霞, 伦立德. 中国血液净化, 2018, 17(4), 229—233) |
11 | Zhang Y., Liu Y. Y., Xiao G. Q., Shao Y. H., Mei C. L., Kong Y. Z., Journal of Clinical Nephrology, 2017, 17(6), 345—348(张豫, 刘园园, 肖观清, 邵咏红, 梅长林, 孔耀中. 临床肾脏病杂志, 2017, 17(6), 345—348) |
12 | Huang X. B., Preparation of Hypercrosslinked Polystyrene Resin with Buffering Functional Groups and Study on Its Properties, Master Dissertation of Hunan Normal University, Changsha, 2015(黄小贝, 含pH缓冲功能基超高交联聚苯乙烯吸附剂的合成及性能研究, 长沙: 湖南师范大学, 2015) |
13 | Zheng C. G., Preparation of Low⁃chlorine⁃content Hypercrosslinked Polystyrene Resin and Its Properties, Master Dissertation of Hunan Normal University, Changsha, 2015(郑从光. 低氯含量超高交联聚苯乙烯的制备及其性能研究, 长沙: 湖南师范大学, 2014) |
14 | Eleonora R., Mauro C., Maristella M., Gennaro A., Roberta R., Stefania B., Andrea M., Lucia G., Loredana P., Bruna G., PLoS One, 2014, 9(4), e95811 |
15 | Hiroshi W., Tsuyoshi N., Yohei M., Daisuke K., Toru M., Drug Metabolism & Disposition, 2012, 40(7), 1423—1428 |
16 | Ankita V., Mohd R., Naidu S., Gulam R., Rizwan H. K., PLoS One, 2011, 6(2), e17230 |
17 | Nida Z., Mohammad R. A., Gulam R., Ejaz A., Rizwan H. K., PLoS One, 2013, 8(8), e71422 |
18 | Tan L., Tan B., Chemical Society Reviews, 2017, 46(11), 3322—3356 |
19 | Mai W. C., Sun B., Wu D. C., Fu R. W., Acta Polymerica Sinica, 2018,(7), 930—938(麦伟聪, 孙镔, 吴丁财, 符若文. 高分子学报, 2018,(7), 930—938) |
20 | Tank R., Gupta D. C., Journal of Porous Materials, 2009, 16(4), 387—392 |
21 | Wang R. X., Gao B. J., Journal of Functional Polymers, 2010, (3), 275—280(王蕊欣, 高保娇. 功能高分子学报, 2010, (3), 275—280) |
22 | Tsyurupa M. P., Blinnikova Z. K., Davidovich Y. A., Lyubimov S. E., Naumkin A. V., Davankov V. A., Reactive & Functional Polymers, 2012, 72(12), 973—982 |
23 | Moulder J., Stickle W. F., Sobol P. E., Bomben K. D., Chastain J., Handbook of X⁃ray Electron Spectroscopy: A Reference Book of Standard Spectra for Identification and Interpretation of XPS Data, Perkin⁃Elmer Corporation, Minnesota, USA, 1992 |
24 | Ang A. K. S., Kang E. T., Neoh K. G., Tan K. L., Lim T. B., Polymer, 2000, 41(2), 489—498 |
25 | Hu T. L., Yu Y. S., Chinese Journal of Nephrology, Dialysis & Transplantation, 2010, 19(1), 78—83(胡炀琳, 俞雨生. 肾脏病与透析肾移植杂志, 2010, 19(1), 78—83) |
26 | Foo K. Y., Hameed B. H., Chem. Eng. J., 2010, 156(1), 2—10 |
27 | Li Q., Zhao W., Guo H., Yang J., Zhang L., ACS Appl. Mater. Interfaces, 2020, 12(23), 25546—25556 |
28 | Zeng X. W., Chen L. J., Fan Y. G., Wang C. H., Shi R. F., Acta Polymerica Sinica, 2009,(9), 909—916(曾小伟, 陈丽娟, 范云鸽, 王春红, 施荣富. 高分子学报, 2009,(9), 909—916) |
29 | Ho Y. S., McKay G., Process Biochem., 1999, 34(5), 451—465 |
30 | Tao G., Zhang L., Hua Z., Chen Y., Shi J., Carbon, 2014, 66(1), 547—559 |
31 | Shi Q., Luan S. F., Jin J., Shi H. C., Yin J. H., Li Y. G., Materials China, 2014, 33(4), 212—223(石强, 栾世方, 金晶, 石恒冲, 殷敬华, 李勇刚. 中国材料进展, 2014, 33(4), 212—223) |
32 | Ma C. F., Gao Q., Zhou J., Chen Q. X., Han B., Xia K. S., Zhou C. G., RSC Adv., 2017,(7), 2081—2091 |
33 | Gu H., Zhou N. L., Fan Y. T., Wang X. D., Li W. X., Shen J., Chem. J. Chinese Universities, 2013, 34(2), 479—484(顾皓, 周宁琳, 樊云婷, 王晓丹, 李文秀, 沈健. 高等学校化学学报, 2013, 34(2), 479—484) |
34 | Liu Y., Peng X., Hu Z., Yu M., Fu J., Huang Y., Materials Science and Engineering: C, 2021, 121, 111879 |
[1] | 汤毅达, 周宁琳, 陆春燕, 金素星, 吴悦, 沈健. 羧基化氧化石墨烯的可控合成及血液相容性[J]. 高等学校化学学报, 2012, 33(11): 2378. |
[2] | 薛歆, 范立双, 牛利, 刘斌, 常静, 张晶, 张基昌, 赵雷, 赵卓, 李淑梅. 316L钢表面纳米银镀层的制备、性质及血液相容性[J]. 高等学校化学学报, 2012, 33(10): 2289. |
[3] | 谢槟, 李贵才, 代璐, 杨苹, 黄楠. 基于多巴胺自聚合及肝素固定改善钛的血液相容性[J]. 高等学校化学学报, 2012, 33(01): 90. |
[4] | 徐东 周宁琳 沈健. 羧基化氧化石墨烯的血液相容性[J]. 高等学校化学学报, 2010, 31(12): 2354. |
[5] | 彭采宇, 仝维鋆, 韩宝三, 王兆海, 高长有, 沈家骢. 不同表面性质聚电解质多层膜的制备及蛋白质吸附和血液相容性能[J]. 高等学校化学学报, 2009, 30(11): 2311. |
[6] | 王蔚,贾小华,刘媛,王亮,袁直,汤石明,刘民,汤华 . 新型含悬挂羧基聚乳酸的制备及其血液相容性和细胞粘附性[J]. 高等学校化学学报, 2008, 29(2): 433. |
[7] | 李瑞军 李德耀 张现峰 任冬春 刘宏民. 大孔吸附树脂法去除淫羊藿多糖中蛋白的研究[J]. 高等学校化学学报, 2006, 27(1): 67. |
[8] | 侯光辉, 王慧彦, 刘涛, 袁直, 房杰, 李冬华, 邱奇, 郭世铎. 以氨基酸为配体的血液灌流用内毒素吸附剂的制备及性能研究[J]. 高等学校化学学报, 2005, 26(7): 1277. |
[9] | 王慧彦, 侯光辉, 俞玫, 袁直, 刘斌, 赵承梅. 以壳聚糖为载体的内毒素吸附剂[J]. 高等学校化学学报, 2005, 26(4): 680. |
[10] | 张金荣, 陈艳丽, 张静泽, 高巨, 施荣富, 杨益忠, 史作清, 王春红. 孔径均匀、可控的大孔吸附树脂的制备及筛分性能的研究[J]. 高等学校化学学报, 2005, 26(4): 765. |
[11] | 俞玫, 王慧彦, 刘涛, 袁直. 血液灌流用内毒素吸附材料研究[J]. 高等学校化学学报, 2004, 25(8): 1465. |
[12] | 方晖, 魏佼, 俞耀庭. 亲和吸附剂对细菌内毒素吸附性能的研究[J]. 高等学校化学学报, 2004, 25(6): 1056. |
[13] | 王虹, 张明明, 杨眉, 吕健, 袁直, 何炳林, 刘斌, 赵承梅, 沈彬. 尿毒症中分子毒物吸附剂的研究(Ⅲ)——酸性氨基酸修饰交联壳聚糖[J]. 高等学校化学学报, 2004, 25(3): 474. |
[14] | 王瑞芳, 李家政, 史作清, 施荣富, 王重, 欧来良. 树脂吸附层析法分离喜树果中的喜果甙[J]. 高等学校化学学报, 2003, 24(8): 1534. |
[15] | 王重, 史作清, 王瑞芳. 酚醛型吸附树脂对咖啡因和茶碱吸附性能的研究[J]. 高等学校化学学报, 2003, 24(10): 1896. |
阅读次数 | ||||||
全文 |
|
|||||
摘要 |
|
|||||