泡球蚴感染C57BL/6小鼠肝脏CD34表达的动态变化
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摘要
目的观察泡球蚴(Em)感染C57BL/6小鼠肝脏CD34微血管密度(MVD)的动态变化。方法将40只C57BL/6小鼠随机分为实验组和对照组,实验组通过肉眼肝叶穿刺感染泡球蚴(Em),对照组通过注射等量PBS。分别于感染后30 d、60 d、90 d及120 d后取小鼠肝脏组织,苏木素-伊红(HE)染色观察肝脏的病理组织学改变,免疫组织化学染色观察泡球蚴感染后CD34-MVD的动态改变。结果实验组泡球蚴组织各时间点中CD34-MVD分别为(39.10±11.84)/HP、(66.80±11.08)/HP、(111.20±8.00)/HP和(56.14±7.12)/HP,实验组泡球蚴周围肝组织分别为(1.14±0.82)/HP、(1.56±0.92)/HP、(2.32±1.43)/HP和(1.38±0.82)/HP;对照组分别为(1.00±0.94)/HP、(1.30±1.06)/HP、(2.00±1.15)/HP和(1.10±0.87)/HP。实验组与对照组比较,差异均有统计学意义(P<0.01);实验组泡球蚴组织内比较,差异有统计学意义(F=94.63,P<0.001);实验组泡球蚴周围肝组织内比较,差异无统计学意义(F=3.24,P>0.05);对照组内比较,差异无统计学意义(F=1.98,P>0.05)。结论泡球蚴浸润性生长过程中可能伴随着血管新生,血管新生可能为其生长重要的机制之一。
The aim of our study is to observe the dynamic expression of CD34 microvascular density(MVD) in the liver of C57BL/6 mice infected with Echinococcus multilocularis(Em). Forty C57BL/6 mice were randomly divided into two groups,the experimental group and the control group.Each mouse of the experimental group was infected with echinococcus protoscoleces by opening their abdominal in inoculating liver. Each mouse of the control group received a coresponding volume of PBS.After 30 days,60 days,90 days and 120 days,samples of mouse liver were collected and subjected to hematoxylin and eosin(HE) staining.The dynamic changes in liver CD34-MVD expression in C57BL/6 mice infected with Em was analyzed by immunohistochemical method. At different times during the course of Em infection,the expression of CD34-MVD respectively was(39.10 ±11.84)/HP,(66.80±11.08)/HP,(111.20±8.00)/HP,(56.14±7.12)/HP, the Em surrounding tissues was(1.14±0.82)/HP,(1.56±0.92)/HP,(2.32±1.43)/HP,(1.38±0.82)/HP, the control group was(1.00±0.94)/HP,(1.30±1.06)/HP,(2.00±1.15)/HP和(1.10±0.87)/HP. The difference between the experimental group and the control group was statistically significant(P<0.01).The differences among different time points in the experimental group Em tissues were also statistically significant(F=94.63,P<0.001);The differences among different time points in the Em surrounding tissues and the control group were no statistically significant(F=3.24,P>0.05,F=1.98,P>0.05). There might be along with angiogenesis in Em of infiltrated growth,angiogensis could be one of the most important mechanisms for its growth.
The aim of our study is to observe the dynamic expression of CD34 microvascular density(MVD) in the liver of C57BL/6 mice infected with Echinococcus multilocularis(Em). Forty C57BL/6 mice were randomly divided into two groups,the experimental group and the control group.Each mouse of the experimental group was infected with echinococcus protoscoleces by opening their abdominal in inoculating liver. Each mouse of the control group received a coresponding volume of PBS.After 30 days,60 days,90 days and 120 days,samples of mouse liver were collected and subjected to hematoxylin and eosin(HE) staining.The dynamic changes in liver CD34-MVD expression in C57BL/6 mice infected with Em was analyzed by immunohistochemical method. At different times during the course of Em infection,the expression of CD34-MVD respectively was(39.10 ±11.84)/HP,(66.80±11.08)/HP,(111.20±8.00)/HP,(56.14±7.12)/HP, the Em surrounding tissues was(1.14±0.82)/HP,(1.56±0.92)/HP,(2.32±1.43)/HP,(1.38±0.82)/HP, the control group was(1.00±0.94)/HP,(1.30±1.06)/HP,(2.00±1.15)/HP和(1.10±0.87)/HP. The difference between the experimental group and the control group was statistically significant(P<0.01).The differences among different time points in the experimental group Em tissues were also statistically significant(F=94.63,P<0.001);The differences among different time points in the Em surrounding tissues and the control group were no statistically significant(F=3.24,P>0.05,F=1.98,P>0.05). There might be along with angiogenesis in Em of infiltrated growth,angiogensis could be one of the most important mechanisms for its growth.
引文
[1] Piarroux M, Piarroux R, Giorgi R, et al. Clinical features and evolution of alveolar echinococcosis in France from 1982 to 2007: results of a survey in 387 patients[J]. J Hepatol,2011, 55(5):1025-1033.
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[4] Hanahan D. Rethinking the war on cancer[J]. Lancet, 2014, 383(9916):558-563.
[5] Nielsen JS, Mcnagny KM. CD34 is a key regulator of hematopoietic stem cell trafficking to bone marrow and mast cell progenitor trafficking in the periphery[J]. Microcirculation, 2009, 16(6):487-496. DOI:10.1080/10739680902941737
[6] Majchrzak K, Kaspera W, Szyma J, et al. Markers of angiogenesis (CD31, CD34, rCBV) and their prognostic value in low-grade gliomas[J].Neurol Neurochir Pol, 2013, 47(4):325-331.
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[8] 李瑶, 林仁勇, 徐琦,等. 泡球蚴感染对Balb/c小鼠肝脏TGF-β1及其信号蛋白表达的影响[J]. 免疫学杂志, 2011, 27(3):215-220.
[9] Yang P, Yuan W, He J, et al. Overexpression of EphA2, MMP-9, and MVD-CD34 in hepatocellular carcinoma: Implications for tumor progression and prognosis[J]. Hepatol Res, 2010, 39(12):1169-1177. DOI:10.1111/j.1872-034X.2009.00563.x
[10] Bing Z, Jianru Y, Yaoquan J, et al. Evaluation of angiogenesis in non-small cell lung carcinoma by CD34 immunohistochemistry[J].Cell Biochem Biophys, 2014, 70(1):327-331. DOI:10.1007/s12013-014-9916-5
[11] Hristov M, Weber C. Endothelial progenitor cells in vascular repair and remodeling[J]. Pharmacol Res, 2008, 58(2):148-151. DOI: 10.1016/j.phrs.2008.07.008
[12] Siemerink MJ, Klaassen I, Vogels IMC, et al. CD34 marks angiogenic tip cells in human vascular endothelial cell cultures[J]. Angiogenesis, 2012, 15(1):151-163. DOI: 10.1007/s10456-011-9251-z
[13] Sarmadi S, Izadimood N, Movarei F. Association of neo angiogenesis by CD34 expression and clinicopathologic features in squamous cell carcinoma of cervix[J]. Acta Med Iran, 2017, 55(5):282-289.
[14] Mathiyalagan P, Liang Y, Kim D, et al. Angiogenic mechanisms of human CD34\r,+\r, stem cell exosomes in the repair of ischemic hindlimb novelty and significance[J]. Circ Res, 2017, 120(9):1466-1476.
[15] 张示杰, 吴何兴, 李琪,等. 沙鼠肝泡球蚴组织中微血管密度、血管内皮生长因子的表达及意义[J]. 中国普外基础与临床杂志, 2015, 22(2):134-138.
[16] 张继增. 泡状棘球蚴病[J]. 诊断病理学杂志, 2001, 8(5):261-262.
[17] Dematteis S, Baz A, Rottenberg M, et al. Antibody and Th1/Th2-type responses in BALB/c mice inoculated with live or dead Echinococcus granulosus protoscoleces.[J]. Parasite Immunol, 2010, 21(1):19-26.
[18] Wang J, Gottstein B. Immunoregulation in larval Echinococcus multilocularis infection[J]. Parasite Immunol, 2016, 38(3):182-192.
[19] 魏晓丽, 丁剑冰, 许晏,等. 小鼠感染泡球蚴后细胞因子水平的变化[J]. 中国寄生虫学与寄生虫病杂志, 2004, 22(6):361-364.
[20] 赵慧, 白雪, 聂晓涵,等. 泡球蚴感染小鼠肝脏中IL-10和TGF-β1的动态变化[J]. 中国寄生虫学与寄生虫病杂志, 2012, 30(1):6-32.
[2] Avcioglu H, Guven E, Balkaya I, et al. First detection of Echinococcus multilocularis in rodent intermediate hosts in Turkey[J].Parasitology, 2017:1-7.
[3] 温浩, 徐明谦. 实用包虫病学[M]. 北京:科学出版社, 2007:16-17.
[4] Hanahan D. Rethinking the war on cancer[J]. Lancet, 2014, 383(9916):558-563.
[5] Nielsen JS, Mcnagny KM. CD34 is a key regulator of hematopoietic stem cell trafficking to bone marrow and mast cell progenitor trafficking in the periphery[J]. Microcirculation, 2009, 16(6):487-496. DOI:10.1080/10739680902941737
[6] Majchrzak K, Kaspera W, Szyma J, et al. Markers of angiogenesis (CD31, CD34, rCBV) and their prognostic value in low-grade gliomas[J].Neurol Neurochir Pol, 2013, 47(4):325-331.
[7] Weidner N, Folkman J, Pozza F, et al. Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma[J].J Natl Cancer I, 1992, 84(24):1875-1887.
[8] 李瑶, 林仁勇, 徐琦,等. 泡球蚴感染对Balb/c小鼠肝脏TGF-β1及其信号蛋白表达的影响[J]. 免疫学杂志, 2011, 27(3):215-220.
[9] Yang P, Yuan W, He J, et al. Overexpression of EphA2, MMP-9, and MVD-CD34 in hepatocellular carcinoma: Implications for tumor progression and prognosis[J]. Hepatol Res, 2010, 39(12):1169-1177. DOI:10.1111/j.1872-034X.2009.00563.x
[10] Bing Z, Jianru Y, Yaoquan J, et al. Evaluation of angiogenesis in non-small cell lung carcinoma by CD34 immunohistochemistry[J].Cell Biochem Biophys, 2014, 70(1):327-331. DOI:10.1007/s12013-014-9916-5
[11] Hristov M, Weber C. Endothelial progenitor cells in vascular repair and remodeling[J]. Pharmacol Res, 2008, 58(2):148-151. DOI: 10.1016/j.phrs.2008.07.008
[12] Siemerink MJ, Klaassen I, Vogels IMC, et al. CD34 marks angiogenic tip cells in human vascular endothelial cell cultures[J]. Angiogenesis, 2012, 15(1):151-163. DOI: 10.1007/s10456-011-9251-z
[13] Sarmadi S, Izadimood N, Movarei F. Association of neo angiogenesis by CD34 expression and clinicopathologic features in squamous cell carcinoma of cervix[J]. Acta Med Iran, 2017, 55(5):282-289.
[14] Mathiyalagan P, Liang Y, Kim D, et al. Angiogenic mechanisms of human CD34\r,+\r, stem cell exosomes in the repair of ischemic hindlimb novelty and significance[J]. Circ Res, 2017, 120(9):1466-1476.
[15] 张示杰, 吴何兴, 李琪,等. 沙鼠肝泡球蚴组织中微血管密度、血管内皮生长因子的表达及意义[J]. 中国普外基础与临床杂志, 2015, 22(2):134-138.
[16] 张继增. 泡状棘球蚴病[J]. 诊断病理学杂志, 2001, 8(5):261-262.
[17] Dematteis S, Baz A, Rottenberg M, et al. Antibody and Th1/Th2-type responses in BALB/c mice inoculated with live or dead Echinococcus granulosus protoscoleces.[J]. Parasite Immunol, 2010, 21(1):19-26.
[18] Wang J, Gottstein B. Immunoregulation in larval Echinococcus multilocularis infection[J]. Parasite Immunol, 2016, 38(3):182-192.
[19] 魏晓丽, 丁剑冰, 许晏,等. 小鼠感染泡球蚴后细胞因子水平的变化[J]. 中国寄生虫学与寄生虫病杂志, 2004, 22(6):361-364.
[20] 赵慧, 白雪, 聂晓涵,等. 泡球蚴感染小鼠肝脏中IL-10和TGF-β1的动态变化[J]. 中国寄生虫学与寄生虫病杂志, 2012, 30(1):6-32.