系膜增生性肾小球肾炎的MR分子成像研究

Mesangial proliferative glomerulonephritis(MsPGN) is one of the important pathological types of primary glomerulonephritis.Mesangial cell proliferation frequently precedes and is linked to the increase of extracellular matrix in the mesangium of MsPGN, which has prominent accordance with clinical manifestation and prognosis.The key point in management of MsPGN is to early diagnose and estimate pathology and progress of glomerulohephritis. Renal biopsy used as golden criteria for kidney disease diagnosis is not considered a routine procudure due to invasive consequense.It's in an urgent need to develop a non-invasive modality to diagnose and assess treatment in MsPGN comprehensively.Integrin ανβ3 is up-regulated in proliferative mesangial cells,which acts as a vital moleular hallmark in MsPGN. Our study is to prepare SPIO-RGD as a molecular probe to visualize Integrin receptors on proliferative mesangial cells in rabbit MsPGN model via MR technique, the goal is to explore a non-invasive method for early diagnosis of MsPGN and provide new perspective for future application in evaluation of theraputic effect and prognosis.

系膜增生性肾小球肾炎(MsPGN)是原发性肾小球肾炎的重要病理类型之一，以弥漫性肾小球系膜细胞增生及系膜基质增多为主要特征。MsPGN的系膜细胞增生程度与临床表现和预后有明显依赖关系，早期准确诊断肾脏病变的病理类型和进展程度，是治疗取得成功的关键。肾穿刺作为肾病诊断的金标准由于其创伤性而难以作为常规检查，因此研发高敏感、高特异性并可以活体全面诊断和评价MsPGN治疗效果的无创性检查方法，成为临床的迫切需求。研究表明：增生系膜细胞整合素ανβ3受体表达显著上调，是MsPGN的一个重要标志物。本研究将利用兔系膜增生性肾炎模型作为研究对象，制备靶向标记整合素ανβ3 受体的SPIO-RGD纳米分子探针，通过MR分子成像活体对MsPGN系膜增生情况在细胞与分子水平进行评估和动态监测，探索早期诊断MsPGN的无创性检查方法，为临床判断预后及疗效提供新思路。

系膜增生性肾小球肾炎(mesangial proliferative glomerulonephritis，MsPGN)是成人原发性肾小球肾炎的重要病理类型之一。MsPGN临床表现和预后与系膜细胞增生程度有明显依赖关系。增生的系膜细胞细胞表面存在高表达的整合素ανβ3，RGD作为整合素ανβ3的配体具有特异性亲和力。我们的研究制备磁性探针SPIO-RGD并进行体外和活体实验，验证了MsPGN肾病模型皮质区在注射造影剂后T2值有明显减低，普鲁士蓝染色显示在增生的系膜系膜细胞区有大量蓝染颗粒沉积,提示SPIO-RGD可以有效无创诊断MsPGN并通过MR参数进行定量测量。在完成以上实验之外，利用已建成模型进行了肾病的功能成像研究，测量了病变区域ADC值和FA值的变化，提出功能成像可以在血清学检查阴性阶段早期就对病理改变给予警示，具有极大的临床应用价值。