IgA肾病肾内小动脉病变特点及其可能发生机制

Characteristics of intrarenal arteriole lesions and its possible pathogenesis in patients with IgA nephropathy

目的观察伴或不伴高血压的IgA肾病患者肾内小/细动脉病变特点及其可能的机制。方法选取光镜表现为轻度系膜增生或局灶增生性病变伴小/细动脉病变的原发性IgA肾病20例,其中血压正常者10例为A组,伴高血压者10例为B组,非IgA轻度系膜增生或局灶增生性肾炎血压正常者10例为C组,3组临床及病理指标相匹配。对经皮肾穿刺活检组织常规进行免疫荧光、光镜(HE、PASM、Masson染色)及电镜检查。选取PASM染色切片,使用多功能电子显微镜,在200倍视野下,选取小/细动脉的正中或接近正中矢状位横截面照相,使用医学图像分析管理系统测量管壁厚度/血管外径、内膜厚度/血管外径、中膜厚度/血管外径。采用免疫组化法检测肾组织及小/细动脉血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)、血管紧张素Ⅱ1型受体(angiotensinⅡtype1receptor,AT1R)及Ⅲ型胶原纤维的表达。结果 A、B组与C组相比管壁厚度/血管外径、内膜厚度/血管外径显著升高,A组与B组间差异无统计学意义(P>0.05)。小/细动脉区域与肾组织AngⅡ、AT1R表达强度一致(P>0.05)。A、B组与C组相比,肾组织及小/细动脉区域AngⅡ与AT1R表达显著增强,B组与A组相比,除AngⅡ在肾组织的表达增强外,小/细动脉AngⅡ及AT1R在肾组织及小/细动脉的表达差异均无统计学意义(均P>0.05);Ⅲ型胶原纤维主要分布于小/细动脉内膜,B组较A、C组显著增强,A、C两组间差异无统计学意义(P>0.05)。IgA肾病肾内小/细动脉病变的相关因素分析显示:管壁厚度/血管外径与其AngⅡ表达呈显著正相关,内膜厚度/血管外径与AngⅡ、AT1R表达呈显著正相关。结论 IgA肾病患者肾内小/细动脉病变不完全依赖于高血压,其肾内肾素-血管肾张素系统的表达明显增强。

Objective To characterize the intrarenal arteriole lesions and the possible pathogenesis in IgA nephropathy patients with and without hypertension. Methods We retrospectively collected 20 IgA nephropathy patients with mild mesangial hyperplasia or focal hyperplasia associated with intrarenal arteriole lesions. They were divided into two groups： group A with normal blood pressure （n=10）, and group B with hypertension （n=10）. In addition, 10 non-IgA nephropathy cases with mild mesangial hyperplasia or focal hyperplasa and normal blood pressure were assigned as group C. Clinical and pathological indexes were matched among the 3 groups. Renal biopsy tissues were subject to light microscopy after HE, PASM and Masson staining, immunofluorescence and electron microscopy examinations. Cross section images of arterioles in the slides were taken after staining with PASM. The wall thickness/outer diameter ratio and intima thickness/outer diameter ratio of the arterioles were then measured. AngiotensinII （Ang II）, AngiotensinII receptor type I （AT1R） and collagen III in slides were detected by immunohistochemistry. Results The wall thickness/outer diameter ratio and intima thickness/outer diameter ratio of the arterioles were significantly higher in groups A and B than in group C, but were indifferent between group A and B. The expression of AngII and AT1R in renal tissues and arterioles were significantly higher in groups A and B than in group C. AngII expression in renal tissues was significantly higher in group B than in group A, but AngII expression in arterioles and AT1R expression in renal tissues and arterioles were similar between the 2 groups. Collagen III expressed predominantly in arteriolar intima, and was significantly higher in group B than in groups A and C. Positive correlations between wall thickness/outer diameter ratio and AngII expression as well as between intima thickness/outer diameter ratio and the expressions of AngII and AT1R were found in arterioles. Conclusion In IgA nephropathy patients, the intrarenal arteriole lesions did not completely depend on hypertention, and the intrarenal rennin-angiotensin system is highly expressed.