基于异常糖基化IgA1研究和解法抑制肾系膜细胞增殖的机制

IgA nephropathy is mostly attributed to respiratory and gastrointestinal tract infection，the abnormal-glycosylated IgA1 is the cause of IgA1 accumulating in glomerular mesangium. The pathogenesis of IgA nephropathy is similar to the route of transmission known as “exogenous pathogens invading from the exterior into the interior “in the Chinese medicine. Our study showed that Reconciliation and Heat-clearing Decoction could significantly reduce the proteinuria and hematuria for the cases with IgA nephropathy. The Animal study suggested that Reconciliation and Heat-clearing Decoction could also reduce the abnormal-glycosylated IgA1 in serum and the development of renal mesangial cells and extracellular matrix could be slowed down.But further studies are required on how to reduce the abnormal-glycosylated IgA1 by this decoction. The latest research shows that the down-regulating Cosmc expression can increase the amount of abnormal-glycosylated IgA1 in peripheral lymphocytes; And it also shows that the decreasing combination of abnormal-glycosylated IgA1 and ASGP-R in liver cells eliminates the abnormal ones. The project is intended to use animal experiment and cell culture in vitro to make further study on the mechanism of how Reconciliation and Heat-clearing Decoction reduce the abnormal-glycosylated IgA1 and how it inhibits the proliferation to reduce cytokine-causing proinflammatory and fibrosis by testing the level of Cosmc expression and the cohesion of ASGP-R.

IgA肾病的发生多与呼吸道、胃肠道感染有关，IgA1糖基化异常在IgA1沉积到肾小球系膜中起着重要作用，其发病机制与中医“邪气由表入里”的传变途径认识相似。我们前期研究发现具有和解清热作用的中药可有效降低IgA肾病患者的尿蛋白量、改善血尿，能降低IgA肾病大鼠血液和肾组织中异常糖基化IgA1的量，并减轻肾组织中系膜细胞和基质增生。但该方如何减少异常糖基化IgA1的机制有待进一步研究。最新研究显示B淋巴细胞Cosmc表达减少使IgA1不能正常糖基化而异常糖基化IgA1产生增多，而与肝细胞ASGP-R结合的能力下降是异常糖基化IgA1清除减少的原因。本项目拟采用肾系膜细胞体外培养和动物实验的方法，通过检测B淋巴细胞Cosmc的表达量、肝脏ASGP-R结合力等，进一步研究和解清热方减少异常糖基化IgA1、抑制系膜细胞增殖、减少其产生促炎症和纤维化的细胞因子的机制。

IgA肾病的发生多与呼吸道、胃肠道感染有关，IgA1糖基化异常在IgA1沉积到肾小球系膜中起着重要作用，其发病机制与中医“邪气由表入里”的传变途径认识相似。我们前期研究发现具有和解清热作用的中药可有效降低IgA肾病患者的尿蛋白量、改善血尿，能降低IgA肾病大鼠血液和肾组织中异常糖基化IgA1的量，并减轻肾组织中系膜细胞和基质增生。最新研究显示B淋巴细胞Cosmc表达减少使IgA1不能正常糖基化而异常糖基化IgA1产生增多，而与肝细胞ASGP-R结合的能力下降是异常糖基化IgA1清除减少的原因。本项目采用肾系膜细胞体外培养和动物实验的方法，通过检测B淋巴细胞Cosmc的表达量、肝脏ASGP-R结合力等，进一步研究和解清热方减少异常糖基化IgA1、抑制系膜细胞增殖、减少其产生促炎症和纤维化的细胞因子的机制。在体外人肾系膜细胞培养实验中，具有和解法立法组方的粘膜方能上调IgA肾病患者外周B淋巴细胞的Cosmc mRNA和蛋白的表达水平，并下调IgA肾病患者外周B淋巴细胞的TGF-β1和蛋白的表达水平。