Determination of 29 Trace Elements in 32 Cases of Liver Biopsy with Unexplained Liver Injury
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摘要:
目的 测定肝组织中的微量元素,探讨不明原因肝损害的发生与机体微量元素的关系。 方法 对不明原因肝损害患者进行肝组织穿刺术取出肝组织,与对照组正常的肝组织,均采用电感耦合等离子体质谱仪测定29种微量元素含量,进行比较分析。 结果 不明原因肝损害(实验组)与对照组比较,肝组织中的锂7Li、铍9Be、铝27Al、钙44Ca、钛48Ti、钒51V、铬52Cr、钴59Co、镍60Ni、锗73Ge、锶88Sr 、 钼95Mo 、铟115In、锡118Sn、铼185Re、铂195Pt、汞202Hg、铅208Pb、铋209Bi 19种元素均显著增高,差异有统计学意义(P < 0.01);砷75As、硒82Se均增高,差异有统计学意义(P < 0.05),镉111Cd显著降低 ,差异有统计学意义(P < 0.01),而镁24Mg、锰55Mn、铁57Fe、铜63Cu、锌66Zn、镓71Ga、硒77Se、钡137Ba无显著差异(P > 0.05)。 实验组中铁蛋白和肝组织活检中铁含量的相关性,采用Spearman相关性分析,P < 0.01,铁蛋白与肝组织中铁呈正相关关系。 结论 不明原因肝损害患者的肝组织中微量元素升高,表明这些微量元素代谢异常可能为不明原因肝损害的原因之一,或在肝病的发生、发展过程中起一定的作用。肝病理检查及肝组织微量元素测定为实验组患者明确找到了肝损害的病因。铁蛋白与肝组织中铁含量呈正相关。 Abstract:Objective To determine trace elements in liver tissue and to explore the relationship between the occurrence of liver injury with unknown causes and trace elements in the body. Methods The liver tissue of patients with liver injury of unknown causes was obtained by liver biopsy. The content of 29 trace elements was determined by inductively coupled plasma mass spectrometry (ICP-MS) and were compared with the normal liver tissue of the control group. Results Compared with the control group, 19 elements including lithium, beryllium, aluminum, calcium, titanium, vanadium, chromium, cobalt, nickel, germanium, strontium, molybdenum, indium, tin, rhenium, platinum, mercury, lead, bismuth were significantly increased (P < 0.01). Arsenic and selenium increased (P < 0.05), and cadmium significantly decreased (P < 0.01). However, there were no significant differences in magnesium, manganese, ferrum, copper, zinc, gallium, selenium and barium (P > 0.05). Spearman correlation analysis showed ferritin was positively correlated with iron content in liver tissue. Conclusion The increase of trace elements in liver tissue of patients with liver injury of unknown cause indicated that abnormal metabolism of trace elements might be one of the causes of liver injury of unknown causes or play a certain role in the occurrence and development of liver disease. By examination of liver pathology and determination of trace elements in liver tissue, the causes of liver damage in the experimental group were clearly found. Ferritin was positively correlated with iron content in liver tissue. -
表 1 实验组与对照组肝组织中的微量元素含量(μg/g)
Table 1. The concentration of trace elements in liver tissue of experimental group and control group (μg/g )
元素 对照组M(P25,P75) 实验组M(P25,P75) Z P 锂Li7 0.415 (0.166,0.562) 1.380 (0.653,2.838) −4.034 < 0.001** 铍Be9 0.031 (0.017,0.043) 0.807 (0.339,1.284) −5.191 < 0.001** 镁Mg24 191.410 (116.950,253.097) 134.812 (82.114,232.670) −1.343 0.179 铝Al27 91.708 (60.774,128.017) 205.687 (79.968,293.438) −3.137 0.002** 钙Ca44 31.559 (19.419,42.835) 121.298 (53.201,331.890) −4.494 < 0.001** 钛Ti48 3.311 (2.258,4.655) 15.650 (6.840,23.429) −5.593 < 0.001** 钒V51 0.056 (0.040,0.090) 0.469 (0.166,0.894) −5.560 < 0.001** 铬Cr52 0.750 (0.4298,1.199) 3.041 (1.965,5.828) −5.699 < 0.001** 锰Mn55 4.544 (2.759,5.413) 3.583 (2.622,8.520) −4.02 0.688 铁Fe57 1104.256 (872.058,1902.449) 1092.648 (712.147,1709.335) −0.715 0.474 钴Co59 0.213 (0.178,0.251) 0.780 (0.350,4.161) −4.743 < 0.001** 镍Ni60 1.739 (1.004,2.467) 8.945 (4.652,18.341) −5.496 < 0.001** 铜Cu63 39.023 (23.287,47.266) 44.792 (26.534,60.657) −1.356 0.175 锌 Zn66 140.601 (101.656,182.848) 95.770 (57.136,181.653) −1.574 0.116 镓Ga71 0.394 (0.232,0.640) 0.326 (0.116,0.668) −0.487 0.626 锗Ge73 0.044 (0.032,0.079) 0.162 (0.057,0.361) −3.223 0.001 ** 砷 As75 0.857 (0.436,1.596) 1.923 (0.475,4.566) −2.080 0.038 * 硒Se77 1.407 (0.950,2.377) 1.646 (0.899,2.204) −0.315 0.753 硒Se82 0.892 (0.589,1.237) 1.317 (0.701,2.850) −2.277 0.023* 锶Sr88 1.527 (0.841,2.135) 3.305 (1.459,4.520) −3.758 < 0.001** 钼Mo95 2.168 (1.506,2.790) 3.206 (1.749,7.236) −2.637 0.008 镉Cd111 6.818 (2.942,10.272) 1.408 (0.660,1.731) −5.364 < 0.001** 铟Ln115 0.004 (0.002,0.006) 0.108 (0.075,0.497) −5.892 < 0.001** 锡Sn118 0.633 (0.359,0.836) 4.994 (2.015,36.284) −4.136 < 0.001** 钡Ba137 50.791 (27.999,63.054) 52.746 (27.407,85.671) −0.752 0.452 铼Re185 0.000 (0.000,0.001) 0.143 (0.028,0.340) −5.122 < 0.001** 铂Pt195 0.005 (0.003,0.010) 0.259 (0.095,0.428) −4.928 < 0.001** 汞Hg202 0.281 (0.167,0.378) 5.140 (2.275,10.034) −4.774 < 0.001** 铅Pb208 3.927 (3.007,6.485) 16.921 (8.302,30.566) −5.034 < 0.001** 铋Bi209 0.217 (0.148,0.557) 0.895 (0.525,2.507) −3.689 < 0.001** *P < 0.05, **P < 0.01。 表 2 实验组与对照组肝组织中的微量元素升高及降低例数[n(%)]
Table 2. The number of trace elements in liver tissue increased and decreased in experimental group and control group [n(%)]
元素名 参数(P25,P75) 实验组 对照组 增高 降低 实检n 增高n(%) 降低n(%) 实检n 增高n(%) 降低n(%) χ2 P χ2 P 锂7Li (0.166,0.562) 27 13 (48.148) 3 (11.111) 33 5 (15.152) 3 (9.091) 7.699 0.006** − 0.796 铍9Be (0.017,0.043) 18 13 (72.222) 2 (11.111) 26 7 (26.923) 5 (19.231) 8.803 0.003** − 0.469 镁24Mg (116.950,253.097) 31 4 (12.903) 10 (32.258) 35 8 (24.242) 8 (24.242) 1.095 0.295 0.732 0.392 铝27Al (60.774,128.017) 31 19(61.290) 5(16.129) 33 5 (15.150) 10(30.303) 14.518 < 0.001** 1.790 0.181 钙44Ca (19.419,42.835) 32 25(78.125) 3 (9.375) 35 4 (11.428) 10(28.571) 30.291 < 0.001** 3.939 0.047 钛48Ti (2.258,4.655) 30 26(86.667) 1 (3.333) 35 7 (20.000) 9 (25.714) 28.725 < 0.001** − 0.016* 钒51V (0.040,0.090) 30 24(80.000) 1 (3.333) 33 6 (18.182) 5 (15.152) 24.075 < 0.001** − 0.197 铬52Cr (0.4298,1.199) 32 24(75.000) 2 (6.250) 35 8 (22.857) 8 (22.857) 18.216 < 0.001** − 0.086 锰55Mn (2.759,5.413) 32 12(37.500) 11 (34.375) 35 5 (14.286) 9 (25.714) 4.758 0.029* 0.599 0.439 铁57Fe (872.058,1902.449) 32 6(18.750) 14 (43.750) 35 8 (22.857) 9 (25.714) 0.171 0.680 2.412 0.120 钴59Co (0.178,0.251) 31 22 (70.968) 6 (19.355) 32 6 (18.750) 6 (18.750) 17.389 < 0.001** 0.004 0.951 镍60Ni (1.004,2.467) 30 23 (76.667) 2 (66.667) 31 10(32.258) 6 (19.355) 12.108 0.001** − 0.255 铜63Cu (23.287,47.266) 32 17 (53.125) 5 (15.625) 35 6 (17.143) 8 (22.857) 10.289 0.001** 0.559 0.455 锌66Zn (101.656,182.848) 31 9 (29.032) 14 (45.161) 35 7 (20.000) 9 (25.714) 0.730 0.393 2.738 0.098 镓71Ga (0.232,0.640) 25 5(20.000) 12 (48.000) 35 8 (22.857) 8 (22.857) 0.070 0.791 4.149 0.042 锗73Ge (0.032,0.079) 27 12 (44.444) 6 (22.222) 34 7 (20.588) 8 (23.529) 3.994 0.046* 0.015 0.904 砷75As (0.436,1.596) 28 8 (28.571) 8 (28.571) 31 5 (16.129) 6 (19.355) 1.326 0.250 0.691 0.406 硒77Se (0.950,2.377) 31 7 (22.581) 7 (22.581) 35 9 (25.714) 8 (22.857) 0.088 0.767 0.001 0.979 硒82Se (0.589,1.237) 31 16 (51.613) 4 (12.903) 35 7 (20.000) 9 (25.714) 7.236 0.007** 1.706 0.192 锶88Sr (0.841,2.135) 31 18 (58.065) 5 (16.129) 35 6 (17.143) 9 (25.714) 11.897 0.001** 0.904 0.342 钼95Mo (1.506,2.790) 30 13 (43.333) 9 (30.000) 34 7 (20.588) 8 (23.529) 3.838 0.050 0.342 0.559 镉111Cd (2.942,10.272) 31 1 (3.225) 25 (80.645) 35 7 (20.000) 7 (20.000) − 0.058 24.207 < 0.001** 铟115In (0.002,0.006) 20 16 (80.000) 1 (5.000) 27 6 (22.222) 9 (33.33) 15.405 < 0.001** − 0.029* 锡118Sn (0.359,0.836) 28 18 (64.286) 3 (10.714) 14 2 (14.286) 2 (14.286) 9.355 0.002** − 0.736 钡137Ba (27.999,63.054) 31 11(35.484) 11 (35.484) 35 2 (5.714) 9 (25.714) 9.211 0.002** 0.743 0.389 铼185Re (0.000,0.001) 22 17 (77.272) 0 (0.000) 27 4 (14.815) 0 (0.000) 19.310 < 0.001** 铂195Pt (0.003,0.010) 28 24 (85.714) 1 (3.571) 17 2 (11.764) 2 (11.764) 23.712 < 0.001** − 0.547 汞202Hg (0.167,0.378) 26 17 (65.385) 4 (15.385) 34 6 (17.647) 7 (20.688) 14.203 < 0.001** − 0.742 铅208Pb (3.007,6.485) 32 22 (68.750) 3 (9.375) 35 6 (17.143) 8 (22.857) 18.302 < 0.001** 2.214 0.137 铋209Bi (0.148,0.557) 28 16 (57.143) 6 (21.429) 31 2 (6.452) 9 (29.032) 17.831 < 0.001** 0.449 0.503 *P < 0.05,**P < 0.01。 表 3 中毒性肝炎组肝组织的微量元素升高情况 (μg/g)
Table 3. The increase of trace elements in liver tissues in the group of toxic hepatitis (μg/g)
元素 对照组M(P25,P75) 中毒性肝炎组M(P25,P75) Z P 钙44Ca 31.559 (19.419,42.835) 357.595 (38.793,511.147) −2.556 0.011* 钛48Ti 3.311 (2.258,4.655) 17.322 (7.353,51.076) −3.251 0.001** 钒51V 0.056 (0.040,0.090) 0.280 (0.110,1.115) −3.153 0.002** 铬52Cr 0.750 (0.4298,1.199) 5.859 (2.623,12.030) −3.415 0.001** 钴59Co 0.213 (0.178,0.251) 1.261 (0.247,3.134) −2.221 0.026* 镍60Ni 1.739 (1.004,2.467) 10.018 (8.526,18.814) −3.545 < 0.001** 镉11Cd 6.818 (2.942,10.272) 0.941 (0.639,2.132) −2.924 0.003* 铟115In 0.004 (0.002,0.006) 0.6335 (0.063,0.000) −2.325 0.020* 铼185Re 0.000 (0.000,0.001) 0.000 (0.000,0.000) −2.336 0.020* 铂195Pt 0.005 (0.003,0.010) 0.418 (0.093,3.058) −3.174 0.002** 铅208Pb 3.927 (3.007,6.485) 25.501 (19.160,40.517) −3.415 0.001** *P < 0.05, **P < 0.01 。 表 4 实验组铁蛋白和肝组织活检中铁含量及相关性比较
Table 4. Comparison of iron content and correlation between ferritin and liver biopsy in experimental group
项目 P50 P25 P75 铁蛋白(ng/mL) 300.90 161.78 914.15 Fe [ppb] 1244.01 950.96 2032.84 rS 0.888 P < 0.001** **P < 0.01。 -
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