人类系膜增生性肾炎(MsPGN)发病率高，其早期病变涉及肾小球系膜细胞(GMCs)的凋亡，但其凋亡的机制尚未阐明。亚溶解型 (sublytic) C5b-9是GMCs凋亡的启动原已被确认。我们先前的研究发现，大鼠Thy-1肾炎(MsPGN模型)早期，肾内既可查见sublytic C5b-9的沉积，又能见到GMCs凋亡。鉴于转录辅激活子p300和转录因子Egr-1及ATF3在Thy-1肾炎(体内)和sublytic C5b-9刺激的GMCs (体外)中均明显上调，故为了探讨Thy-1肾炎的免疫病理学机制，本研究拟从体内外探讨由sublytic C5b-9刺激上调的p300、Egr-1、ATF3及Egr-1或ATF3被p300乙酰化修饰后对GMCs凋亡的影响，包括Egr-1与ATF3之间的关系。旨在为揭示Thy-1肾炎GMCs凋亡的关键分子及其表观遗传学调控机制，并为防治MsPGN提供启示。

Human mesangial proliferative glomerulonephritis (MsPGN) is a disease with high incidence, and the apoptosis of glomerular mesangial cells (GMCs) in the early stage of MsPGN has been confirmed, but the mechanism of GMCs apoptosis remains unclear. It has been demonstrated that sublytic C5b-9 complex is a trigger for GMCs apoptosis. And our previous studies revealed that glomerular sublytic C5b-9 deposition and GMCs apoptosis were seen in the early stage of rat Thy-1 nephritis (a model of human MsPGN). Given that transcriptional coactivator p300 and transcription factors such as the early growth responsive gene-1 (Egr-1) and activating transcription factor 3 (ATF3) are significantly up-regulated both in the renal tissue of rats with Thy-1 nephritis (in vivo) and in the GMCs stimulated with sublytic C5b-9 complexes (in vitro), and to explore the immunopathologic mechanism of the GMCs apoptosis in Thy-1 nephritis, we attempt to determine the effects of p300, Egr-1 or ATF3 expression including Egr-1 and (or) ATF3 acetylation modification mediated by p300 on GMCs apoptosis induced by sublytic C5b-9 including the relationship of Egr-1 and ATF3. The aim of this study is to elucidate the key factors resulting in GMCs apoptosis in rat Thy-1 nephritis and epigenetic regulatory mechanism, and further to provide a novel clue for preventing and treating human MsPGN.