血清铁和铁蛋白与肝病患者肝纤维化的相关研究
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摘要
目的 铁过载和许多疾病关系密切,尤其是肝脏疾病。如何有效地控制肝铁过载,对于肝病的预防和治疗都有着重要的意义。本文对血清铁,血清铁蛋白和肝脏疾病肝纤维化指标的关系及肝铁过载的问题加以研究,为肝病的预防和治疗提供客观的参考指标。方法 用1S快速肝穿刺法,对36例肝病患者肝组织标本行HE和铁染色、镜检;同时分别应用原子吸收光谱法,放射免疫法和酶联免疫法检测患者的血清铁,铁蛋白和肝纤维化指标(包括透明质酸,层粘蛋白,人Ⅲ型前胶原,Ⅳ型胶原)。结果 良性肝病患者与肝细胞癌患者比较,血清铁测定值无显著性差异(P>0.05),但早期肝细胞癌患者肝纤维化指标明显高于良性肝病患者(P<0.05)。血清铁和血清铁蛋白与层粘蛋白具有统计学上的相关性(血清铁r=0.428,p=0.029;血清铁蛋白r=0.465,p=0.018)。肝癌组织没有发现铁颗粒沉积。结论 肝细胞癌患者多出现血清铁蛋白升高;血清铁、血清铁蛋白测定值和层粘蛋白测定值具有相关性;与良性肝病相比,肝癌组织的铁含量明显降低。晚期肝癌患者纤维化指标下降,可能与肿瘤组织抑制了胶原合成有关。酒精性脂肪肝多合并肝铁过载;对于良性肝脏疾病血清铁蛋白测定值可以作为肝铁过载的重要指标。
Objective To study the relationship of serum iron and ferritin with the indicators for hepatic fibrosis. Methods To use the method of one second liver biopsy, liver tissue speciments were obtained from 36 patients with benign (14)or malign (22)liver diseases, and routine microscopic examination was performed after haematoxylin—eosin(HE) and Perl's Prussian staining. Atomic absorption spectrum, radioimmunoassay and enzyme—linked immunosorbent assay were respectively employed to examine the serum levels of iron, ferritin, hyaluronic acid, laminin, human procollagen typeⅢ, and collagen typeⅣ. Results The results between patients with benign and malignant liver diseases are significant differences in the serum ferritin levels (P<0.05), but not in serum iron levels (P>0.05 ). It was also noted that the levels of the indicators for hepatic fibrosis in patients with begin and early—stage malignant disease varied significantly from the levels in normal subjects ,but these differences were not observed between normal subjects and patients with end—stage hepatic malignancies. Serum iron and ferritin were found to be associated with serum laminin levels (serum iron: r=0.428, p=0.029;serum ferritin: r=0.465, p=0.018 ), and no irongranules detected in the tissue specimens of hepatocellular carcinoma. Conclusions Most of the patients with hepatocellular carcinoma have elevated serum ferritin levels. The serum levels of iron and ferritin are statistically correlated with serum laminin level. Obvious reduction of iron content is typical of hepatic malignant tissuesin comparison with the benign tissues, and the reduction in the levels of the indicators for hepatic fibrosis might involve the inhibition of collagen synthesis in the tumor tissues from patients with end-stage hepatocellular carcinoma. Most of the cases of alcoholic fatty liver are complicated by liver iron overload, often marked by serum iron and ferrtin levels.
Objective To study the relationship of serum iron and ferritin with the indicators for hepatic fibrosis. Methods To use the method of one second liver biopsy, liver tissue speciments were obtained from 36 patients with benign (14)or malign (22)liver diseases, and routine microscopic examination was performed after haematoxylin—eosin(HE) and Perl's Prussian staining. Atomic absorption spectrum, radioimmunoassay and enzyme—linked immunosorbent assay were respectively employed to examine the serum levels of iron, ferritin, hyaluronic acid, laminin, human procollagen typeⅢ, and collagen typeⅣ. Results The results between patients with benign and malignant liver diseases are significant differences in the serum ferritin levels (P<0.05), but not in serum iron levels (P>0.05 ). It was also noted that the levels of the indicators for hepatic fibrosis in patients with begin and early—stage malignant disease varied significantly from the levels in normal subjects ,but these differences were not observed between normal subjects and patients with end—stage hepatic malignancies. Serum iron and ferritin were found to be associated with serum laminin levels (serum iron: r=0.428, p=0.029;serum ferritin: r=0.465, p=0.018 ), and no irongranules detected in the tissue specimens of hepatocellular carcinoma. Conclusions Most of the patients with hepatocellular carcinoma have elevated serum ferritin levels. The serum levels of iron and ferritin are statistically correlated with serum laminin level. Obvious reduction of iron content is typical of hepatic malignant tissuesin comparison with the benign tissues, and the reduction in the levels of the indicators for hepatic fibrosis might involve the inhibition of collagen synthesis in the tumor tissues from patients with end-stage hepatocellular carcinoma. Most of the cases of alcoholic fatty liver are complicated by liver iron overload, often marked by serum iron and ferrtin levels.
引文
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2.李增禧,梁业成.铁是生命牧关的微量元素.广东省微量元素科学.1994;1(3):54-5
3.黄聪武,白岚.铁过载和肝脏疾病.第一军医大学学报.2002;22(4):370-1
4.范建民,曾民德.脂肪肝.上海医科大学出版社,2000,6.49-50
5.张雪生,柳启沛.乙醇对铁过载大鼠肝细胞脂质过氧化和胶原代谢的影响.营养学报1998:20(4):432-435
6. Siegers CP. Influence of dietary iron overload on cell proliferution and intestinal tumorgenesis in mice. Can felt, 19921 65(3): 245-246
7. Wixom RI, Prukin L. Henosiderin: Nature, formation, and significance. Rev Exp pathol, 1998;22(2): 193-195
8.叶维法,杨秉辉.肝胆肿瘤学.天津科学技术出版社,2000,40-41
9. Harrison H, Adams PC. Hemochromatosis. Commongenes, uncommon illness? Can Fam Physiciaw, 2002;48(15): 132633
10. Hoshida Y, Ikcda k. Chromic Liver disense in the extremely elderly of 80 years or more: Clinicnl chaltheristion proghosis and patient survival analysis. Hepatol, 1999: 31(5): 860-866
11. Ronach H, Fataccioli V. Effect of chronic ethanol feeding on lipid peroxidation and protein oxidation in relation to liver pathology. Hepatology, 1997;25(2): 351-355
12. Pinelli A, TrivnlZio S, Tomasoni L. High-dose vitamin E lovers urine porphyrin levels in patients affected by porphyria cutanca tarda. Pharmacol Res. 2002;45(4):355-359
13.Bayraktar Y. The use of deferoxamine infusions to enhance the response role to interferon-alpha threatment of chronic viral hepatitis B. J Viral Hepat, 1996;3(3)129-135
14. Grandal N, Milman N. Distribution of liver haemosiderin iron in 187 patients with variors types of hepatic disease. APMIS, 1996;104(3): 220-226
15. 江绍基.临床肝胆系病学.上海科学技术出版社,1992:433—440
16. Torimuru T. Cooldinated expression of integrin α6β1 and lamin hepatocellular carcinoma. Hum Pathol, 1997;28(10):1131
2.李增禧,梁业成.铁是生命牧关的微量元素.广东省微量元素科学.1994;1(3):54-5
3.黄聪武,白岚.铁过载和肝脏疾病.第一军医大学学报.2002;22(4):370-1
4.范建民,曾民德.脂肪肝.上海医科大学出版社,2000,6.49-50
5.张雪生,柳启沛.乙醇对铁过载大鼠肝细胞脂质过氧化和胶原代谢的影响.营养学报1998:20(4):432-435
6. Siegers CP. Influence of dietary iron overload on cell proliferution and intestinal tumorgenesis in mice. Can felt, 19921 65(3): 245-246
7. Wixom RI, Prukin L. Henosiderin: Nature, formation, and significance. Rev Exp pathol, 1998;22(2): 193-195
8.叶维法,杨秉辉.肝胆肿瘤学.天津科学技术出版社,2000,40-41
9. Harrison H, Adams PC. Hemochromatosis. Commongenes, uncommon illness? Can Fam Physiciaw, 2002;48(15): 132633
10. Hoshida Y, Ikcda k. Chromic Liver disense in the extremely elderly of 80 years or more: Clinicnl chaltheristion proghosis and patient survival analysis. Hepatol, 1999: 31(5): 860-866
11. Ronach H, Fataccioli V. Effect of chronic ethanol feeding on lipid peroxidation and protein oxidation in relation to liver pathology. Hepatology, 1997;25(2): 351-355
12. Pinelli A, TrivnlZio S, Tomasoni L. High-dose vitamin E lovers urine porphyrin levels in patients affected by porphyria cutanca tarda. Pharmacol Res. 2002;45(4):355-359
13.Bayraktar Y. The use of deferoxamine infusions to enhance the response role to interferon-alpha threatment of chronic viral hepatitis B. J Viral Hepat, 1996;3(3)129-135
14. Grandal N, Milman N. Distribution of liver haemosiderin iron in 187 patients with variors types of hepatic disease. APMIS, 1996;104(3): 220-226
15. 江绍基.临床肝胆系病学.上海科学技术出版社,1992:433—440
16. Torimuru T. Cooldinated expression of integrin α6β1 and lamin hepatocellular carcinoma. Hum Pathol, 1997;28(10):1131