霉酚酸酯治疗对狼疮性肾炎肾组织内α-SMA和TGF-β_1的影响

Expression of renal α-SMA and TGF-β_1 in lupus nephritis patients treated with mycophenolate mofetil

目的 :研究霉酚酸酯 (MMF)对狼疮性肾炎 (LN)肾脏慢性化病变的影响。 方法 :9例LN患者采用MMF联合中小剂量激素疗法。免疫组化法检测治疗前后肾内α 平滑肌肌动蛋白 (α SMA)和转化生长因子 β1(TGF β1)的表达。 结果 :MMF治疗 6个月后 ,LN患者的蛋白尿、自身抗体等临床指标均获得明显改善 ,肾组织慢性化指数治疗前后改变无统计学差异 (P >0 0 5 )。患者肾小球内α SMA的表达明显减少 (P <0 0 5 ) ,而肾小管间质中α SMA和肾内TGF β1的表达治疗后有部分下降但无统计学意义。肾间质血管上α SMA的表达治疗前后无明显差异。结论 :MMF治疗 6个月后 ,患者肾内α SMA和TGF β1的表达部分下降 ,可能是肾脏慢性化病变无明显进展的重要原因之一。

Objective:To investigate the effect of mycophenolate mofetil(MMF)on chronic renal lesions in patients with active lupus nephritis(LN)and the related pharmacologic mechanisms. Methodology:MMF was given to nine active LN patients at a dosage of 1 0～1 5 g/d and oral prednisone for six months.All renal biopsy and vebiospy (6 months later) samples were processed for routine staining,and renal chronic index of each patient was evaluated. Α smooth muscle actin(α SMA)and transforming growth factor β 1(TGF β 1)protein expression were assessed by immunohistochemistry staining. Results:Urinary protein excretion and anti ds DNA antibody titer of the patients were significantly decreased after six months treatment of MMF(3 39±2 66 g/24h vs 0 74±0 70 g/24h and 20 3±18 0% vs 2 93±4 24%,Both P <0 01).Although serum creatinine levels of the patients improved to a certain degree after 6 months MMF treatment,but the difference had no statistical significance (131 6±115 6 μmol/L vs 75 6±31 7 μmol/L, P >0 05).Chronic index of renal pathology was found no significant increase after treatment with MMF(2 33±2 00 vs 2 67±2 50, P >0 05).Glomerulosclerosis,fibrotic crescents,tubular atrophy,interstitial fibrosis and arteriolar fibrosis were found not aggravated after treatment.Protein expression of α SMA in glomerular decreased dramatically after six months treatment of MMF (1 69±1 17 vs 0 99±0 63, P <0 05).The renal protein expression of TGF β 1(1 51±0 70 vs 1 07±0 54 in glomerular;1 67±0 56 vs 1 02±0 43 in tubulointerstitium;Both P >0 05)was estimated and α SMA in tubulointerstitium(1 84±0 68 vs 1 83±0 53, P >0 05)was reduced at certain extent after treatment,but showed no statistical significance.Protein expression of α SMA on interstitial vessels was found no obvious difference before and after MMF treatment. Conclusion:Protein expression of glomerular α SMA and renal TGF β 1 decreased significantly after six months treatment of MMF,which might be related with the unchanged chronic renal index.