【作者】 李素敏；

【导师】 段惠军；

【作者基本信息】 河北医科大学 ， 病理学与病理生理学， 2006， 博士

【摘要】 目的:IgA肾病自1968年首先报导以来,已被认为是世界上最常见的原发性肾小球疾病。初期,人们认为该病预后良好。近年研究发现,在确诊后20～25年内患者呈进行性发展,20%～30%不可逆转地进展为终末期肾病(end-stage renal disease,ESRD)。肾组织学分级系统有助于比较IgAN肾活检标本和预测自然病程。本文首先回顾性研究既往6年678例IgAN肾活检标本,分析肾脏组织学分级及肾小管间质损害(TIL)与临床、实验室资料之间的关系。其次,研究不同级别的TIL肾活检组织中结缔组织生长因子(CTGF),磷酸化P38有丝分裂原活化蛋白激酶(phosphorylaed-P38 mitogen activated protein kinase,P-P38MAPK)及转化生长因子(TGF-β1)的表达情况,并探讨它们在肾小管间质损害进程中的作用。并进一步前瞻性对照研究IgA肾病患者Th细胞亚群紊乱与临床表现、TIL之间的关系,及其在发病机制中的作用。最后,探讨了黄芪注射液对IgAN患者肾小管功能的影响,并分析肾小管功能(尿视黄醇结合蛋白Urinary retinol binding protein,RBP及尿N-乙酰-β-D氨基葡萄糖苷酶N-acetyl-β-D- glucosaminidase,UNAG)与IgA肾病患者间质病理损害程度之间的关系,为进一步研究IgA肾病的发病机制及防治措施提供理论依据。方法:1.678例IgA肾病肾小管间质损害与临床指标的相关分析收集经临床及肾活检证实的678例原发性IgA肾病患者的病理与临床资料。光镜下观察方法:参考Lee分级标准和Haas分型标准,并根据小管间质损害病理学特点,对肾小管间质病变严重程度采用半定量积分评价。比较不同类型肾小管间质病变IgA肾病患者之间临床表现、实验室检查及肾活检病理的特点。2.IgA肾病患者CTGF、P38MAPK在TGF-β1致肾脏纤维化中的作用肾小管-间质病理指标参考Haas分型标准,将IgAN患者分为下列三组:1.轻度增生组(HaasⅠ、Ⅱ型)2.局灶增生组(HaasⅢ型)3.增生硬化组更多还原

【Abstract】 Objectives: IgA nephropathy (IgAN) was first described in 1968 and is now recognized as the commonest primary glomerulopathy.The long-term outcome was initially thought to be benign but several series have reported highly variable prognosis with up to 20～30% of patients with IgAN developing end-stage renal disease (ESRD) within 20～25 years of diagnosis.The histologic grading system is useful to compare biopsy specimens and to predict the natural course of disease in IgA nephropathy (IgAN), although none of grading system is perfect. Firstly,The purpose of this retrospective study over a period of 6 years 678 renal biopsies was to investigate the relationship of the histologic grading, tubulointerstitial lesions(TIL) and clinical,laboratory data. secondly,To study the expression of connective tissue growth factor(CTGF), the phosphorylaed p38 Mitogen-Activated Protein Kinase (p-p38MAPK) Mediates TGF-β1–Induced Fibrogenesis in renal tissues of patients with IgA nephropathy. and theirs relationship with different grade tubulointerstital lession (TIL).Thirdly,To investigate the relationship of imbalance of T cell subpopulations and pathogenesis, clinical manifestation, as well as TIL of IgA nephropathy in prospective and controlled trial. Finally, To probe the effects of astragalus injection (AI) on renal tubular function in patients with IgAN and analyze the relationship of the renal tubular function (urinary retinol binding protein,RBP;N-acetyl-β-D-glucosaminidase,UNAG) and the severity of tubulointerstitial lesion. In order to further investigate the pathogenesis and preventional measure of IgA nephropathy.Methods:1. Study on the associations of the tubulointerstitial lesions with clinical indices in 678 cases of IgA nephropathyThe clinical、laboratory and histopathological data in 678 patients with更多还原