Identification and regulation of factors related to progression of renal

主要研究结果如下：(1)基于前期研究发现足细胞损伤可使系膜损伤引起的可逆损伤转变为不可逆损伤，通过同时注射抗裂膜单克隆抗体（5-1-6）和抗y-1单克隆抗体（1-223），建立了大鼠进行性肾脏病变的不可逆模型。(2)肾小球内fractalkine表达的增加和肾小球内CX3CR1（fractalkine受体）阳性细胞浸润的增加与肾脏病变的进展密切相关。(3)针对cd4阳性细胞或Th1细胞因子或FK506 （Th1细胞因子阻滞剂）以及FTY720、MMF、螺内酯和ACE抑制剂的抗体可抑制肾脏病变的进展。(4)胶原酶活性降低是系膜基质增加的良好标志。(5)在mRNA水平上抑制tgf - β的表达可抑制系膜基质的增加。(6)中药、GTW可抑制Thy-1型肾炎患者尿蛋白、肾小球系膜基质增加及MCP-2、IL-2表达。(7)早期干预低蛋白饮食可延缓肾脏疾病的进展。

Summarized main results are : (1)A new irreversible model for progressive renal lesions has been established in rats by injecting simultaneously the anti-slit diaphragm monoclonal antibody (5-1-6) and anti-Thy-1 monoclonal antibody (1-22-3), based on our previous finding that podocyte injury could change the reversible injury derived from the mesangial injury to the irreversible one. (2)The increased intraglomerular expression of fractalkine and the increased intraglomerular infiltration of CX3CR1(receptor to fractalkine)-positive cells were intimately related to the progression of the renal lesions. (3)Antibodies against CD4-positive cells or Th1 cytokines or FK506 (blocker of Th1 cytokines as well as FTY720,MMF, spironolactone and ACE inhibitors suppressed the progression of renal lesions. (4)The decrease in the collagenase activity was a good marker for the increase of mesangial matrix. (5)The suppression of the expression of TGF-beta at mRNA level resulted in the suppression of the increase of mesangial matrix. (6)Traditional Chinese medicine, GTW could suppress the amount of urinary protein, mesangial matrix increase and the expression of MCP-2 and IL-2 expression in Thy-1 nephritis. (7)The eartly intervention with low protein diet could delay the progression of renal diseases.