Alperovich G, Rama I, Lloberas N, Franquesa M, Poveda R, Gomà M, Herrero-Fresneda I, Cruzado J M, Bolaños N, Carrera M, Grinyó J M, Torras J
Laboratori de Nefrologia Experimental, Hospital de Bellvitge, Barcelona, Spain.
Lupus. 2007;16(1):18-24. doi: 10.1177/0961203306073136.
Renal involvement in systemic lupus erythematosus is a common complication that significantly worsens morbidity and mortality. Although treatment with corticosteroids and cytotoxic drugs may be useful in many cases, morbidity associated with these drugs and the relapsing nature of the disease make it necessary to develop new treatment strategies. Five-month old female NZB/W F1 mice were divided into the following groups: CYP group (n = 10), cyclophosphamide (CYP) 50 mg/kg intraperitoneally every 10 days; RAPA 1 group (n = 10) oral daily sirolimus (SRL), 1 mg/kg; RAPA 12 group (n = 13), oral daily SRL, 12mg/kg; FTY group (n = 10), oral fingolimod (FTY720), 2 mg/kg three times per week. An additional group of 13 non-treated mice were used as a control (control group). Follow-up was performed over four months. Animal survival, body weight, anti-DNA antibodies and proteinuria were determined. Kidneys were processed for conventional histology and immunofluorescence for IgG and complement. Total histological score (HS) was the sum of mesangial expansion, endocapillary proliferation glomerular deposits, extracapillary proliferation, interstitial infiltrates, tubular atrophy and interstitial fibrosis. All treated groups had lower proteinuria at the end of the follow-up with respect to the control group (P < 0.0001). Serum anti-DNA antibodies were appropriately controlled in RAPA 1 and CYP groups, but not in FTY or RAPA 12 groups. SRL and CYP arrested, and perhaps reversed almost all histological lesions. FTY720 ameliorated histological lesions but did not control mesangial expansion or interstitial infiltrates. SRL produces great improvement in murine lupus nephritis, while FTY720 seems a promising alternative if used in appropriate doses.
系统性红斑狼疮累及肾脏是一种常见的并发症，会显著增加发病率和死亡率。尽管在许多情况下使用皮质类固醇和细胞毒性药物进行治疗可能有效，但这些药物相关的发病率以及疾病的复发特性使得有必要开发新的治疗策略。将5月龄雌性NZB/W F1小鼠分为以下几组：环磷酰胺（CYP）组（n = 10），每10天腹腔注射环磷酰胺（CYP）50 mg/kg；雷帕霉素1组（n = 10），每日口服西罗莫司（SRL）1 mg/kg；雷帕霉素12组（n = 13），每日口服西罗莫司（SRL）12 mg/kg；芬戈莫德（FTY）组（n = 10），每周三次口服芬戈莫德（FTY720）2 mg/kg。另外选取13只未治疗的小鼠作为对照组。随访进行了四个月。测定动物存活率、体重、抗DNA抗体和蛋白尿。对肾脏进行常规组织学检查以及IgG和补体的免疫荧光检查。总组织学评分（HS）为系膜扩张、毛细血管内增生、肾小球沉积物、毛细血管外增生、间质浸润、肾小管萎缩和间质纤维化的总和。与对照组相比，所有治疗组在随访结束时蛋白尿水平均较低（P < 0.0001）。雷帕霉素1组和环磷酰胺组血清抗DNA抗体得到适当控制，但在芬戈莫德组或雷帕霉素12组中未得到控制。西罗莫司和环磷酰胺阻止了几乎所有组织学病变，甚至可能使其逆转。芬戈莫德改善了组织学病变，但未控制系膜扩张或间质浸润。西罗莫司对小鼠狼疮性肾炎有显著改善作用，而芬戈莫德如果使用适当剂量似乎是一种有前景的替代药物。
