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中华诊断学电子杂志

中华诊断学电子杂志 ›› 2024, Vol. 12 ›› Issue (03) : 160 -165. doi: 10.3877/cma.j.issn.2095-655X.2024.03.004

基础研究

质子磁共振波谱对急性肝损伤兔肝脏脂质与葡萄糖代谢评估价值的研究
关计添1, 尤克增2, 耿义群3, 孙树宜4, 赖凌峰4, 沈智威1, 张晓磊1, 周腾5, 黄淮栋4, 杨琳4, 程焱4, 吴烁华4, 赵芝泓4, 庄彩玉4, 吴仁华1,†()   
  1. 1. 515041　汕头大学医学院第二附属医院影像科；515041　汕头大学医学院第二附属医院医学影像中心
    2. 515041　汕头大学医学院第二附属医院影像科；276400　临沂市中心医院医学影像科
    3. 515000　汕头大学医学院分子病理实验室
    4. 515041　汕头大学医学院第二附属医院影像科
    5. 515000　汕头大学医学院计算机系
  • 收稿日期:2024-04-12 出版日期:2024-08-26
  • 通信作者: 吴仁华
  • 基金资助:
    国家自然科学基金(31870981); 国家自然科学基金重点国际（地区）合作研究项目(82020108016); 2020 LKSF跨学科研究项目(2020LKSFBME06); 2020李嘉诚基金会跨学科研究项目(2020LKSFG05D); 广东省高水平大学发展计划临床医学重点学科项目(002-18120302); 广东省科技专项基金项目(STKJ2021148); 广东省基础与应用基础研究基金省企联合基金(2023A1515220187); 广东省基础与应用基础研究基金自然科学基金项目(2024A1515012267)

The value of proton magnetic resonance spectroscopy in assessing liver lipid and glucose metabolism alternations in rabbits with acute liver injury

Jitian Guan1, Kezeng You2, Yiqun Geng3, Shuyi Sun4, Lingfeng Lai4, Zhiwei Shen1, Xiaolei Zhang1, Teng Zhou5, Huaidong Huang4, Lin Yang4, Yan Cheng4, Shuohua Wu4, Zhihong Zhao4, Caiyu Zhuang4, Renhua Wu1,†()   

  1. 1. Department of Radiology, the Second Affiliated Hospital of Medical College of Shantou University, Shantou 515041, China; Department of Medical Imaging Center, the Second Affiliated Hospital of Medical College of Shantou University, Shantou 515041, China
    2. Department of Radiology, the Second Affiliated Hospital of Medical College of Shantou University, Shantou 515041, China; Department of Imaging Center, the Linyi Central Hospital, Linyi 276400, China
    3. Laboratory of Molecular Pathology, Medical College of Shantou University, Shantou 515000, China
    4. Department of Radiology, the Second Affiliated Hospital of Medical College of Shantou University, Shantou 515041, China
    5. Department of Computer Science, Medical College of Shantou University, Shantou 515000, China
  • Received:2024-04-12 Published:2024-08-26
  • Corresponding author: Renhua Wu
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引用本文：

关计添, 尤克增, 耿义群, 孙树宜, 赖凌峰, 沈智威, 张晓磊, 周腾, 黄淮栋, 杨琳, 程焱, 吴烁华, 赵芝泓, 庄彩玉, 吴仁华. 质子磁共振波谱对急性肝损伤兔肝脏脂质与葡萄糖代谢评估价值的研究[J]. 中华诊断学电子杂志, 2024, 12(03): 160-165.

Jitian Guan, Kezeng You, Yiqun Geng, Shuyi Sun, Lingfeng Lai, Zhiwei Shen, Xiaolei Zhang, Teng Zhou, Huaidong Huang, Lin Yang, Yan Cheng, Shuohua Wu, Zhihong Zhao, Caiyu Zhuang, Renhua Wu. The value of proton magnetic resonance spectroscopy in assessing liver lipid and glucose metabolism alternations in rabbits with acute liver injury[J]. Chinese Journal of Diagnostics(Electronic Edition), 2024, 12(03): 160-165.

目的

探究质子磁共振波谱(1H-MRS)技术对兔急性肝损伤模型中肝脏脂质和葡萄糖代谢改变的评估价值。

方法

选择健康成年雄性新西兰大白兔20只，采用随机数字表法分为对照组(10只)和实验组(10只)。对照组腹腔注射生理盐水(1 ml/kg)；实验组腹腔注射亚硒酸钠(1 ml/kg)，构建急性肝损伤模型。48 h后，使用1.5 T磁共振系统，采用单体素点分辨法波谱成像序列扫描兔活体肝脏。使用LCModel软件计算脂质、糖原和葡萄糖复合物(Glyu)和胆碱复合物(CCC)与水的相对峰值，并检测兔血清天冬氨酸转氨酶(AST)和丙氨酸转氨酶(ALT)水平，两组比较采用t检验。对兔肝脏标本进行苏木精-伊红(HE)染色，观察肝脏组织病理学变化。

结果

19只动物最终完成该实验过程，其中实验组9只，对照组10只。与对照组比较，实验组兔的lipid 13/lipid 09水平(5.21±1.83，7.17±2.56)、lipid 13/(lipid 21＋lip 23)水平(6.52±0.82，7.35±2.33)均显著升高，而Glyu水平[(0.22±0.15)×10－2，(0.15±0.06)×10－2]和CCC水平[(0.09±0.03)×10－2，(0.07±0.03)×10－2]则显著下降，均差异有统计学意义(t＝－2.31，－2.88，2.42，2.12；均P<0.05)。实验组兔血清AST[(433.79±140.19)U/L]和ALT[(779.67±149.54)U/L]水平较对照组[(46.51±17.71)U/L，(69.44±20.79)U/L]均显著升高(t＝5.46，13.92；均P<0.05)。实验组兔肝脏出现肝小叶结构破坏、肝细胞坏死等急性弥漫性肝损伤的病理变化。

结论

利用亚硒酸钠可成功诱导兔急性肝损伤。1H-MRS技术可有效评估急性肝损伤的脂质与葡萄糖代谢改变，为临床无创诊断提供了新的思路。

关键词: 化学与药物性肝损伤, 磁共振波谱, 脂质, 葡萄糖
Objective

To investigate the value of proton magnetic resonance spectroscopy (1H-MRS) in assessing liver lipid and glucose metabolism alterations in a rabbit model of acute liver injury.

Methods

Twenty healthy adult male New Zealand white rabbits were randomly divided into a control group (n=10) and an experimental group (n=10). The control group received intraperitoneal injection of normal saline (1 ml/kg), while the experimental group received intraperitoneal injection of sodium selenite (1 ml/kg) to establish an acute liver injury model. After 48 hours, the 1.5 T magnetic resonance system was used to scan the live rabbit liver using a single-voxel point resolved spectroscopy sequence. LCModel software was employed to calculate the relative peaks of lipid, glycogen and glucose complex (Glyu), and choline-containing compounds (CCC) with water, and the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in rabbit serum were measured. Comparisons between the 2 groups were performed using t-tests. The rabbit liver specimens were stained with hematoxylin and eosin (HE) to observe pathological changes in liver tissues.

Results

Nineteen animals ultimately completed the experimental process, with 9 in the experimental group and 10 in the control group. Compared to the control group, the experimental group showed significantly increased levels of lipid 13/lipid 09 (5.21±1.83, 7.17±2.56) and lipid 13/(lipid 21+ lipid 23) (6.52±0.82, 7.35±2.33), while the levels of Glyu [(0.22±0.15)×10-2, (0.15±0.06)×10-2] and CCC [(0.09±0.03)×10-2, (0.07±0.03)×10-2] significantly decreased, all with statistically significant differences (t=-2.31, -2.88, 2.42, 2.12, all P<0.05). Serum AST [(433.79±140.19)U/L, (46.51±17.71)U/L] and ALT [(779.67±149.54)U/L, 69.44±20.79)U/L] levels in the experimental group and control group were also significantly elevated (t=5.46, 13.92, all P<0.05). The livers in the experimental group displayed pathological changes acute diffuse liver injury, such as destruction of the liver lobule structure and necrosis of liver cells.

Conclusions

Sodium selenite can effectively induced acute liver injury in the rabbit model. 1H-MRS technology is proved to be a valuable tool for evaluating the metabolic of lipid and glucose associated with acute liver injury, offering a novel perspective for clinical non-invasive diagnostic strategies.

Key words: Chemical and drug induced liver injury, Magnetic resonance spectroscopy, Lipid, Glucose
图1 兔肝脏质子磁共振波谱图像注：a图为T2加权轴向图像定位图，图中标注单体素MRS定位位置及大小(方框所示)；b图为兔肝脏1H-MRS图，分为lipid 09甲基(-CH3)峰、lipid 13亚甲基(-CH2-)峰、不饱和脂肪酸(-CH2-CH＝CH-CH)峰；CCC为胆碱复合物；Glyu为糖原和葡萄糖复合物；1H-MRS为质子磁共振波谱
表1 两组兔1H-MRS相对代谢物峰值比较(±s)
组别 例数 lipid 13/lipid 09 lipid 13/(lipid 21＋lipid 23) Glyu(×10－2) CCC(×10－2)
实验组 9 7.17±2.56 7.35±2.33 0.15±0.06 0.07±0.03
对照组 10 5.21±1.83 6.52±0.82 0.22±0.15 0.09±0.03
t值   －2.31 －2.88 2.42 2.12
P值   <0.05 <0.05 <0.05 <0.05
表2 两组兔1H-MRS肝功能比较(U/L，±s)
组别 例数 AST ALT
实验组 9 433.79±140.19 779.67±149.54
对照组 10 46.51±17.71 69.44±20.79
t值   5.46 13.92
P值   <0.05 <0.05
图2 两组兔肝脏的组织学切片图像注：a图为对照组；b图为实验组，显示中度细胞肿胀和脂肪变性，并伴有坏死和/或游离出血点(箭头所示)(HE ×100)
[1]
Stine JG，Lewis JH.Current and future directions in the treatment and prevention of drug-induced liver injury：a systematic review[J].Expert Rev Gastroenterol Hepatol，2016，10(4)：517-536.DOI：10.1586/17474124.2016.1127756.
[2]
Chayanupatkul M, Schiano TD. Acute liver failure secondary to drug-induced liver injury[J].Clin Liver Dis，2020，24(1)：75-87.DOI：10.1016/j.cld.2019.09.005.
[3]
Whitfield JB, Masson S, Liangpunsakul S, et al. Evaluation of laboratory tests for cirrhosis and for alcohol use，in the context of alcoholic cirrhosis[J].Alcohol，2018(66)：1-7.DOI：10.1016/j.alcohol.2017.07.006.
[4]
Spallholz JE.On the nature of selenium toxicity and carcinostatic activity[J].Free Radic Biol Med，1994，17(1)：45-64.DOI：10.1016/0891-5849(94)90007-8.
[5]
Siegelman ES，Rosen MA.Imaging of hepatic steatosis[J].Semin Liver Dis，2001，21(1)：71-80.DOI：10.1055/s-2001-12930.
[6]
Choi SJ，Kim SM，Kim YS，et al.Magnetic resonance-based assessments better capture pathophysiologic profiles and progression in nonalcoholic fatty liver disease[J].Diabetes Metab J，2021，45(5)：739-752.DOI：10.4093/dmj.2020.0137.
[7]
Weerasekera A, Sima DM, Dresselaers T, et al. Non-invasive assessment of disease progression and neuroprotective effects of dietary coconut oil supplementation in the ALS SOD1(G93A) mouse model：a (1)H-magnetic resonance spectroscopic study[J].Neuroimage Clin，2018(20)：1092-1105.DOI：10.1016/j.nicl.2018.09.011.
[8]
Dezortova M, Taimr P, Skoch A, et al. Etiology and functional status of liver cirrhosis by 31P MR spectroscopy[J].World J Gastroenterol，2005，11(44)：6926-6931.DOI：10.3748/wjg.v11.i44.6926.
[9]
Smith B，Johnson R，Williams C，et al.Unraveling the glycogen synthesis pathway using 13C nuclear magnetic resonance analysis：a contemporary approach[J].Metabolism，2021(110)：154394.DOI：10.1016/j.metabol.2020.154394.
[10]
Keshavan MS，Stanley JA，Montrose DM，et al.Prefrontal membrane phospholipid metabolism of child and adolescent offspring at risk for schizophrenia or schizoaffective disorder：an in vivo 31P MRS study[J].Mol Psychiatry，2003，8(3)：316-323，251.DOI：10.1038/sj.mp.4001325.
[11]
Wang L，Zhang Y，Chen H，et al.In vivo proton magnetic resonance spectroscopy of hepatic ischemia/reperfusion injury in a rat model：insights from a longitudinal study[J].Magn Reson Imaging，2024(59)：54-61.DOI：10.1016/j.mri.2023.09.012.
[12]
Marjańska M，Terpstra M．Influence of fitting approaches in LCModel on MRS quantification focusing on age-specific macromolecules and the spline baseline[J].NMR Biomed，2021，34(5)：e4197.DOI：10.1002/nbm.4197.
[13]
Takanashi J，Somazawa F，Maruyama K，et al.Metabolic changes in early childhood using LCModel with corrected water scaling method[J].J Magn Reson Imaging，2012，35(1)：174-180.DOI：10.1002/jmri.22802.
[14]
Li T，Zhang H，Yuan X，et al.Lipid metabolism in cancer cells：novel insights from proton nuclear magnetic resonance spectroscopy[J].Trends Biochem Sci，2023，48(5)：411-421.DOI：10.1016/j.tibs.2023.02.004.
[15]
Orphanidou-Vlachou E，Kohe SE，Brundler MA，et al.Metabolite levels in paediatric brain tumours correlate with histological features[J].Pathobiology，2018，85(3)：157-168.DOI：10.1159/000458423.
[16]
Arlauckas SP，Browning EA，Poptani H，et al.Imaging of cancer lipid metabolism in response to therapy[J].NMR Biomed，2019，32(10)：e4070.DOI：10.1002/nbm.4070.
[17]
Romanska HM, Tiziani S, Howe RC, et al. Nuclear magnetic resonance detects phosphoinositide 3-kinase/Akt-independent traits common to pluripotent murine embryonic stem cells and their malignant counterparts[J].Neoplasia，2009，11(12)：1301-1308.DOI：10.1593/neo.09850.
[18]
Carballeira NM，Montano N，Amador LA，et al.Novel very long-chain α-methoxylated δ5，9 fatty acids from the sponge asteropus niger are effective inhibitors of topoisomerases IB[J].Lipids，2016，51(2)：245-256.DOI：10.1007/s11745-015-4114-9.
[19]
Corbin IR，Furth EE，Pickup S，et al.In vivo assessment of hepatic triglycerides in murine non-alcoholic fatty liver disease using magnetic resonance spectroscopy[J].Biochim Biophys Acta，2009，1791(8)：757-763.DOI：10.1016/j.bbalip.2009.02.014.
[20]
Cai C，Wu Y，Yang L，et al.Sodium selenite attenuates balloon injury-induced and monocrotaline-induced vascular remodeling in rats[J].Front Pharmacol，2021 (12)：618493.DOI：10.3389/fphar.2021.618493.
[21]
Reischauer C，Hock A，Kolokythas O，et al.Fully navigated 3 T proton magnetic resonance spectroscopy of liver metastases with inner-volume saturation[J].Abdom Radiol (NY)，2017，42(11)：2615-2622.DOI：10.1007/s00261-017-1173-9.
[22]
Harper DG, Plante DT, Jensen JE, et al. Energetic and cell membrane metabolic products in patients with primary insomnia：a 31-phosphorus magnetic resonance spectroscopy study at 4 tesla[J].Sleep，2013，36(4)：493-500.doi：10.5665/sleep.2530.
[23]
Brandão LA，Castillo M．Adult brain tumors：clinical applications of magnetic resonance spectroscopy[J].Magn Reson Imaging Clin N Am，2016，24(4)：781-809.DOI：10.1016/j.mric.2016.07.005.
[24]
Zarifi M，Tzika AA.Proton MRS imaging in pediatric brain tumors[J].Pediatr Radiol，2016，46(7)：952-962.DOI：10.1007/s00247-016-3547-5.
[25]
Vladimirov N, Perlman O. Molecular MRI-based monitoring of cancer immunotherapy treatment response[J].Int J Mol Sci，2023，24(4)：3151.DOI：10.3390/ijms24043151.
[26]
Kim S，Lee H，Park E，et al.In vivo 1H MR spectroscopic imaging of phospholipase-mediated membrane lipid release in apoptotic glioma：a translational study[J].Neuro Oncol，2023，25(4)：582-591.DOI：10.1093/neuonc/noab045.
[27]
Cao Z，Wu LP，Li YX，et al.Change of choline compounds in sodium selenite-induced apoptosis of rats used as quantitative analysis by in vitro 9.4T MR spectroscopy[J].World J Gastroenterol，2008，14(24)：3891-3896.DOI：10.3748/wjg.14.3891.
[28]
Shen ZW，Cao Z，You KZ，et al.Quantification of choline concentration following liver cell apoptosis using 1H magnetic resonance spectroscopy[J].World J Gastroenterol，2012，18(10)：1130-1136.DOI：10.3748/wjg.v18.i10.1130.
[29]
Alnahdi A，John A，Raza H．Augmentation of glucotoxicity，oxidative stress，apoptosis and mitochondrial dysfunction in HepG2 cells by palmitic acid[J].Nutrients，2019，11(9)：1979.DOI：10.3390/nu11091979.
[30]
Pasanta D，Htun KT，Pan J，et al.Magnetic resonance spectroscopy of hepatic fat from fundamental to clinical applications[J].Diagnostics (Basel)，2021，11(5)：842.DOI：10.3390/diagnostics11050842.
[31]
Morita SY，Tsuji T，Terada T．Protocols for enzymatic fluorometric assays to quantify phospholipid classes[J].Int J Mol Sci，2020，21(3)：1032.DOI：10.3390/ijms21031032.
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