目的 探讨维生素D 受体(VDR)在病毒性心肌炎(VMC)小鼠心肌中的表达动态变化和作用。方法 选取120 只4 周龄雄性BALB/c 小鼠,随机分为对照组(n=40)和实验组(n=80),实验组小鼠腹腔注射柯萨奇B3 病毒制备VMC 模型,对照组小鼠腹腔注射等量的DMEM 液作为替代。分别在注射3、7、14和28 d 后各处死15 只实验组小鼠和10 只对照组小鼠,取小鼠心脏标本。用免疫组织化学法检测小鼠心肌组织VDR 的表达动态变化,并用苏木精-伊红染色观察小鼠心肌的病理变化。结果 实验组小鼠接种病毒后VDR表达显著升高,并在第7 天表达水平达到高峰,然后逐渐下降,在第28 天仍处于较高水平(P<0.01);在第3、7、14 和28 天,实验组小鼠VDR 表达水平均高于对照组,差异均有统计学意义(P<0.01);实验组小鼠心肌病理评分变化趋势与VDR 表达变化趋势一致;实验组小鼠心肌VDR 表达水平与其心肌病理变化呈正相关(P<0.01)。结论 VDR可能参与了VMC发病的炎性免疫过程。
Abstract
Objective To investigate the dynamic expression and role of vitamin D receptor (VDR) in the myocardium of mice with viral myocarditis (VMC).Methods One hundred and twenty 4-week-old male BALB/c mice were selected and assigned into control (n=40) and experimental groups (n=80). The mice in the experimental group were injected intraperitoneally with Coxsackievirus B3 to establish the model of VMC, while the mice in the control group were injected intraperitoneally with an equal volume of DMEM solution. Fifteen mice in the experimental group and ten mice in the control group were sacrificed at 3, 7, 14, or 28 days after injection, and the myocardial specimens were obtained. The dynamic expression of VDR in the myocardium was determined by the immunohistochemical technique. The pathological changes in the myocardium were examined using hematoxylin and eosin staining.Results In the experimental group, the mice had significantly increased expression of VDR after virus injection (P<0.01); the expression of VDR reached the peak at 7 days after injection, and then declined gradually; the expression of VDR remained high at 28 days after injection. At 3, 7, 14, and 28 days after injection, the expression of VDR in the experimental group was significantly higher than that in the control group (P<0.01). Moreover, in the experimental group, the changes in the pathological score of the myocardium were in accordance with the changes in the expression of VDR; the expression level of VDR in the myocardium was positively correlated with the pathological changes in the myocardium in the experimental group (P<0.01).Conclusions VDR may be involved in the inflammatory-immune process in the pathogenesis of VMC.
关键词
病毒性心肌炎 /
维生素D受体 /
维生素D /
小鼠
Key words
Viral myocarditis /
Vitamin D receptor /
Vitamin D /
Mice
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] Hendrickson WK, Flavin R, Kasperzyk JL, et al. Vitamin D receptor protein expression in tumor tissue and prostate cancer progression[J]. J Clin Oncol, 2011, 29(17):2378-2385.
[2] Xiang W, Kong J, Chen S, et al. Cardiac hypertrophy in vitamin D receptor knockout mice:role of the systemic and cardiac renin-angiotensin systems[J]. Am J Physiol Endocrinol Metab, 2005, 288(1):E125-E132.
[3] Girgis CM, Clifton-Bligh RJ, Hamrick MW, et al. The roles of vitamin D in skeletal muscle:form, function, and metabolism[J].Endocr Rev, 2013, 34(1):33-83.
[4] Basson A. Vitamin D and Crohn's disease in the adult patient:a review[J]. JPEN J Parenter Enteral Nutr, 2014, 38(4):438-458.
[5] 郭桂梅, 王娟, 夏敏, 等. 过敏性紫癜患儿血浆 1, 25(OH) 2D3, 维生素 D 受体和 24-羟化酶表达的意义[J]. 中华实用儿科临 床杂志, 2013, 28(21):1640-1642.
[6] Guillot X, Semerano L, Saidenberg-Kermanac'h N, et al. Vitamin D and inflammation[J]. Joint Bone Spine, 2010, 77(6):552-557.
[7] Kahlert C, Bergmann F, Beck J, et al. Low expression of aldehyde deyhdrogenase 1A1 (ALDH1A1) is a prognostic marker for poor survival in pancreatic cancer[J]. BMC Cancer, 2011, 11(1):275-284.
[8] Guo CY, Han B, Chang H, et al. Anti-perforin neutralizing antibody reduces myocardial injury in viral myocarditis[J]. Cardiol Young, 2009, 19(6):601-607.
[9] Jeserich M, Brunner E, Kandolf R, et al. Diagnosis of viral myocarditis by cardiac magnetic resonance and viral genome detection in peripheral blood[J]. Int J Cardiovasc Imaging, 2013, 29(1):121-129.
[10] Yuen S, Smith J, Caruso L, et al. The coxsackie-adenovirus receptor induces an inflammatory cardiomyopathy independent of viral infection[J]. J Mol Cell Cardiol, 2011, 50(5):826-840.
[11] Li K, Xu W, Guo Q, et al. Differential macrophage polarization in male and female BALB/c mice infected with coxsackievirus B3 defines susceptibility to viral myocarditis[J]. Circ Res, 2009, 105(4):353-364.
[12] Huang CH, Vallejo JG, Kollias G, et al. Role of the innate immune system in acute viral myocarditis[J]. Basic Res Cardiol, 2009, 104(3):228-237.
[13] Fairweather D, Frisancho-Kiss S, Njoku DB, et al. Complement receptor 1 and 2 deficiency increases coxsackievirus B3-induced myocarditis, dilated cardiomyopathy, and heart failure by increasing macrophages, IL-1β, and immune complex deposition in the heart[J]. J Immunol, 2006, 176(6):3516-3524.
[14] Yuan J, Yu M, Lin QW, et al. Th17 cells contribute to viral replication in coxsackievirus B3-induced acute viral myocarditis[J]. J Immunol, 2010, 185(7):4004-4010.
[15] 朱慧花, 赵琳. 维生素D 与免疫功能的研究[J]. 医学综述, 2013, 19(5):820-822.
[16] Wittke A, Weaver V, Mahon BD, et al. Vitamin D receptordeficient mice fail to develop experimental allergic asthma[J]. J Immunol, 2004, 173(5):3432-3436.
[17] Querfeld U. Vitamin D and inflammation[J]. Pediatr Nephrol, 2013, 28(4):605-610.
[18] Froicu M, Cantorna MT. Vitamin D and the vitamin D receptor are critical for control of the innate immune response to colonic injury[J]. BMC Immunol, 2007, 8(5):1-11.
[19] Meems LM, Cannon MV, Mahmud H, et al. The vitamin D receptor activator paricalcitol prevents fibrosis and diastolic dysfunction in a murine model of pressure overload[J]. J Steroid Biochem Mol Biol, 2012, 132(3):282-289.
[20] Boonstra A, Barrat FJ, Crain C, et al. 1α, 25-Dihydroxyvitamin D3 has a direct effect on naive CD4+ T cells to enhance the development of Th2 cells[J]. J Immunol, 2001, 167(9):4974-4980.
[21] Fuse K, Kodama M, Aizawa Y, et al. Th1/Th2 balance alteration in the clinical course of a patient with acute viral myocarditis[J]. Jpn Circ J, 2001, 65(12):1082-1084.
PDF(3058 KB)
