35年狼疮性肾炎临床与基础研究

35 Years of Clinical and Basic Research in Lupus Nephritis

本研究在国内首次发现异常增高的循环白介素６ 可导致狼疮性全身性病理损害；白介素６ 异常增高在狼疮性小管间质损害过程中可能具有重要作用；白介素６ 及其信息传递中的 Ｇ Ｐ１３０ ， Ｊｕｎ Ｂ 基因异常表达参与了弥漫性增生性狼疮性肾炎（ Ｌ Ｎ） 分子发病过程，并率先发现丹参通过增强ｃｍｙｃ 蛋白高水平表达而诱导细胞凋亡，从而对人肾成纤维细胞增殖产生抑制作用。在国内外首次证实巨噬细胞在 Ｌ Ｎ 的病人肾脏局部增殖，且和疾病严重程度呈正相关。首次发现白介素受体（ｓ Ｉ Ｌ２ Ｒ） 和 Ｆ Ｌ Ｃ Ｔ 增多是诊断早期活动 Ｌ Ｎ 的可靠指标。筛选并建立了一种本病活动性的计分方法；发现小管间质病变分级对 Ｌ Ｎ 肾小球病理、临床表现、治疗、疗效及复发的判断均有指导意义。在国内首先报道超大剂激素冲击疗法治疗严重的活动性 Ｌ Ｎ，率先提出适合我国国情的改进 Ｃ Ｔ Ｘ 冲击疗法治疗 Ｌ Ｎ。发现中药在促进骨髓造血，对抗 Ｃ Ｔ Ｘ 等致免疫功能过度抑制具有一定作用。首次在国内探讨了 Ｌ Ｎ 尿毒症的可逆性，并分析发现 Ｓ Ｌ Ｅ 死亡最主要原因并非尿毒症。

This research firstly demonstrated that high level of circulating I L 6 plays an importantrolein the patho genesis of systemic damage and renal tubulo interstitial lesions in S L E. The expression of G P130 and Jun Bgenes in thesignaltransduction pathway of I L 6 wasincreased in the pathogenesis of diffuselupus nephritis . Apoptosis can beinducedby enhancement of c myc protein expression , which inhibits proliferation of human kidney fibroblasts . We ,for the firsttime ,demonstrated thatlocal proliferation of macrophages occurs within kidney of patients with lupus nephritis . The ex tent of local macrophage proliferation closely correlated to the severity ofthe diseases . Furthermore ,we found thats I L 2 Rand F L C Tare early parameters oflupus nephritis activity and set up a new activity index scoring system . The severity ofinterstitial damage is closely associated with glomerular damage ,clinical manifestation ,response to therapy , and out comes . We introduced steroid pulse therapyforfulminantlupus and modified C T Xpulse therapy for lupus nephritis . Thepotential role of traditional Chinese medicinesin the treatment oflupus nephritis was proved by its effectiveness in reduc ing side effects of C T X. The reversibility of renalfailure caused by lupus nephritis was also investigated , and the maincause of death in patients with lupus nephritis is mainly non renal.