目的:探讨儿童紫癜性肾炎(HSPN)肾组织Th1/Th2比值与肾脏微血管损伤的关系。方法:选取32名HSPN患儿为病例组,根据肾脏病理结果分为4个亚组:HSPN Ⅱ级(n=8),Ⅲa级(n=7),Ⅲb级(n=10)及Ⅵ/Ⅴ级(n=7)。5例因肾外伤切除肾组织患者为对照组。免疫组化法检测肾组织INFγ(标记Th1细胞)、IL-4(标记Th2细胞)及CD34(标记微血管)的表达,并进行微血管评分,计算微血管密度(MVD),分析肾脏INFγ、IL-4表达与肾脏病理分级、肾脏微血管评分和MVD之间的关系。结果:与对照组相比,病例组肾组织INFγ表达降低,IL-4表达升高,Th1/Th2比值随着HSPN病理损伤的加重而减小,各级间差异有统计学意义(P<0.05)。与对照组比较,HSPNⅡ级和Ⅲa 级组MVD显著增加,但Ⅳ/Ⅴ级组MVD显著减少(P<0.05)。与对照组和HSPNⅡ级组比较,HSPNⅢa级、Ⅲb级以及Ⅳ/Ⅴ级组肾脏微血管评分明显增加,且随病理分级的增加,肾脏微血管评分逐渐增加,各级间差异有统计学意义(P<0.05)。肾组织Th1/Th2比值与微血管密度变化呈负相关(r=-0.921,P<0.01)。结论:Th1/Th2比值降低可能参与了HSPN肾脏微血管损伤。
Abstract
OBJECTIVE: To explore possible correlations between renal Th1/Th2 ratio and renal microvascular injury in children with Henoch-Schonlein purpura nephritis (HSPN). METHODS: Thirty-two children with HSPN were enrolled. They were classified into four groups by renal pathology: HSPN class II (n=8), HSPN class IIIa (n=7), HSPN class IIIb (n=10) and HSPN class IV/V (n=7). Five patients undergoing nephrectomy due to trauma were used as the controls. INFγ, IL-4 and CD34 in the renal tissues were measured by immunohistochemical analysis. INFγ was used as a marker of Th1, IL-4 was used as a marker of Th2 and CD34 was used as a marker of microvessel. The renal microvessel density was evaluated according to the Weidner standard. The relationships among the local Th1/Th2 ratio, renal pathological grade, microvessel score and microvessel density were studied. RESULTS: Immunohistochemical analysis showed a lower expression of INFγ and a higher expression of IL-4 in the HSPN groups than in the control group. The local Th1/Th2 ratio in the HSPN groups decreased and correlated significantly with the renal pathological grade. There were significant differences among four HSPN subgroups (P<0.05). Compared with the control group, the renal microvessel density in the HSPN class II and class IIIa groups increased significantly (P<0.05), but it decreased in the HSPN class IV/V group (P<0.05). The renal microvessel scores in the HSPN class IIIa, class IIIb and class IV/V groups increased significantly compared with those in the control and the HSPN classⅡ. The increased renal microvessel scores were associated with more severe renal pathological changes. A negative correlation was found between the local Th1/Th2 ratio and the microvessel density in kidneys (r=-0.921, P<0.01). CONCLUSIONS: The decrease of Th1/Th2 ratio in kidneys might be responsible for renal microvascular injury in children with HSPN.
关键词
紫癜性肾炎 /
Th1/Th2比值 /
微血管损伤 /
儿童
Key words
Henoch-Schonlein purpura nephritis /
Th1/Th2 ratio /
Microvascular injury /
Child
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1]Del Prete G. The concept of type-1 and type-2 helper T cells and their cytokines in humans[J].Int Rev Immunol, 1998, 16(3-4): 427-455.
[2]Jancovic D, Liu Z, Gause WC. Th1-and Th2-cell commitment during infectious disease: asymmetry in divergent pathways[J].Trends Immunol, 2001, 22(8): 450-457.
[3]Qin W, Hongya W, Yongjing C, Fang X, Yue M, Xuekun Z, et al. Increased OX40 and soluble OX40 ligands in children with Henoch-Schonlein purpura: association with renal involvement[J]. Pediatr Allergy Immunol, 2011, 22(1 Pt 1): 54-59.
[4]周承,王振开. 过敏性紫癜早期肾损害患儿T细胞亚群的变化及意义[J]. 实用临床医药杂志,2009,13(13): 96-98.
[5]陶红,李秋,王莉,李翠萃,阳海平,张高福. 过敏性紫癜发病中树突状细胞与T辅助细胞分化失衡的关系[J]. 第三军医大学学报, 2010, 32(7): 677-679.
[6]杨军,李成荣,祖莹,王国兵,李永柏. 调节性T细胞在儿童过敏性紫癜发病机制中的作用初探[J].中华儿科杂志, 2006, 44(6): 411-414.
[7]孙大庆, 张秋业, 董增义, 白枫. 过敏性紫癜病儿树突细胞分泌白细胞介素12水平与TH1/TH2的变化[J]. 中国当代儿科杂志, 2006, 8(4): 307-310.
[8]许自川,曾雪琪,党西强,何小解. Thl/Th2迁移与紫癜性肾炎的研究进展[J]. 国际病理科学与临床杂志, 2007, 27(1): 64-67.
[9]曾雪琪, 许自川, 党西强, 何小解, 易著文. 血管内皮生长因子与紫癜性肾炎肾间质微血管损伤的关系[J]. 中国当代儿科杂志, 2009, 11(9): 717-721.
[10]张建江,易著文,何小解,杨华彬,丁娟娟,莫双红. 紫癜性肾炎患儿肾间质血管损害与临床的关系[J].实用儿科临床杂志,2006,21(8):487-489.
[11]Kaneyama T, Kobayashi S, Aoyagi D, Ehara T. Tranilast modulates fibrosis, epithelial-mesenchymal transition and peritubular capillary injury in unilateral ureteral obstruction rats[J]. Pathology, 2010, 42(6): 564-573.
[12]Kang DH, Kanellis J, Hugo C, Truong L, Anderson S, Kerjaschki D, et al. Role of The microvascular endothelium in progressive renal disease[J]. J Am Soc Nephrol, 2002, 13(3): 806-816.
[13]Wu L, Tiwari MM, Messer KJ, Holthoff JH, Gokden N, Brock RW, et al. Peritubular capillary dysfunction and renal tubular epithelial cell stress following lipopolysaccharide administration in mice[J]. Am J Physiol Renal Physiol, 2007, 292(1): F261-F268.
[14]Ohashi R, Kitamura H, Yamanaka N. Peritubular capillary injury during the progression of experimental glomerulonephritis in rats[J]. J Am Soc Nephrol, 2000, 11(1): 47-56.
[15]中华医学会儿科学分会肾脏病学组.小儿肾小球疾病的临床分类、诊断及治疗[J].中华儿科杂志, 2001, 39(12):746-749.
[16]Mosmann TR, Coffman Rl. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties[J].Annu Rev Immunol, 1989, 7: 145-173.
[17]Yano T, Tanikawa S, Fujie T, Masutani M, Horie T. Vascular endothelial growth factor expression and neovascularisation in non-small cell lung cancer[J]. Eur J Cancer, 2000, 36(5): 601-609.
[18]Weidner N. Tumoural vascularity as a prognostic in cancer patients: the evidence continues to grow[J]. J Pathol, 1998, 184(2):119-122.
[19]吴杰,陈香美,师锁柱. 血管病变在1005例IgA肾病中的意义及其影响因素[J]. 中华医学杂志, 2003,83(4): 289-293.
[20]解德琼,甘华,杜晓刚,李正荣,巫江.终末期肾病患者Th1/Th2型细胞因子的特征与外周血T细胞凋亡的关系[J].细胞与分子免疫学杂志, 2006, 22(6):763-766.