In vivo (1)H MRS and (31)P MRSI of the response to cyclocreatine in transgenic mouse liver expressing creatine kinase.
In vivo (1)H MRS and (31)P MRSI of the response to cyclocreatine in transgenic mouse liver expressing creatine kinase.
复制标题
表达肌酸激酶的转基因小鼠肝脏对环肌酸反应的体内 (1)H MRS 和 (31)P MRSI。
DOI：
10.1002/nbm.3391
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发表时间：
2015
影响因子：
2.9
通讯作者：
Branch,CraigA
中科院分区：
文献类型：
--
作者：
Cui,Min-Hui;Jayalakshmi,Kamaiah;Liu,Laibin;Guha,Chandan;Branch,CraigA
肝细胞移植已被探索作为肝移植的治疗替代方案，但缺乏监测手术成功的方法。已发表的研究结果支持使用肌酸激酶（CK）表达肝细胞的体内31 P MRSI监测植入肝细胞的增殖。磷酸肌酸组织水平取决于输入到CK酶反应的肌酸（Cr），但通过1H MRS测量Cr的信噪比（SNR）较低。我们研究了使用铬类似物环肌酸的可能性1H MRS和31 P MRSI分别检测CCr对PCCr、γ-ATP、γ-ATP和γ-ATP的影响，在肝细胞中表达CK的BB同种型（CKBB）的转基因小鼠的肝脏中的pH和Pi/ATP。添加1.0%CCr后，第4天肝脏PCCr水平稳定在18.12 ± 3.91 mmol/kg。PCCr与CCr呈正相关，ATP浓度和pH随PCCr的增加而下降。喂食1%CCr水溶液可诱导PCCr明显饱和，表明CCr量化可能不需要用于量化小鼠CK表达。这些发现支持使用31 P MRS无创监测CK表达肝细胞移植成功的可能性。版权所有© 2015约翰威利父子有限公司.
Hepatocyte transplantation has been explored as a therapeutic alternative to liver transplantation, but a means to monitor the success of the procedure is lacking. Published findings support the use ofin vivo31P MRSI of creatine kinase (CK)‐expressing hepatocytes to monitor proliferation of implanted hepatocytes. Phosphocreatine tissue level depends upon creatine (Cr) input to the CK enzyme reaction, but Cr measurement by1H MRS suffers from low signal‐to‐noise ratio (SNR). We examine the possibility of using the Cr analog cyclocreatine (CCr, a substrate for CK), which is quickly phosphorylated to phosphocyclocreatine (PCCr), as a higher SNR alternative to Cr.1H MRS and31P MRSI were employed to measure the effect of incremental supplementation of CCr upon PCCr, γ‐ATP, pH and Pi/ATP in the liver of transgenic mice expressing the BB isoform of CK (CKBB) in hepatocytes.Water supplementation with 0.1% CCr led to a peak total PCCr level of 17.15 ± 1.07 mmol/kg wet weight by 6 weeks, while adding 1.0% CCr led to a stable PCCr liver level of 18.12 ± 3.91 mmol/kg by the fourth day of feeding. PCCr was positively correlated with CCr, and ATP concentration and pH declined with increasing PCCr. Feeding with 1% CCr in water induced an apparent saturated level of PCCr, suggesting that CCr quantization may not be necessary for quantifying expression of CK in mice. These findings support the possibility of using31P MRS to noninvasively monitor hepatocyte transplant success with CK‐expressing hepatocytes. Copyright © 2015 John Wiley & Sons, Ltd.