环孢素影响宿主主要组织相容性复合物的实验研究

目的 研究环孢素对宿主主要组织相容性复合物（MHC）的影响。方法14只新西兰兔随机分成3组,对照组4只,低、高剂量环孢素组各5只,共给药30d。每5天提取外周血单个核细胞RNA,实验结束后取肝脏、脾脏、肾脏和胸腺少许提取RNA,RT-PCR测定MHCI类和MHCⅡ类mRNA的表达,Western印迹测定它们的蛋白表达。结果用药10d时,低剂量环孢素组外周血单个核细胞MHCI类、MHCⅡ类mRNA表达由用药前的0．23±0．04和2．77±0．25分别升高到1．78±0．15和7．30±0．51,蛋白表达由用药前的2．31±0．14和12．52±1．23分别升高到11．32±1．45和22．31±1．91（均P〈0．01）;高剂量环孢素组外周血单个核细胞MHCI类、MHCⅡ类mRNA表达由用药前的0．24±0．06和2．56±0．33分别升高到4．72±0．28和14．20±2．58,蛋白表达由用药前的2．42±0．06和12．51±1．31分别升高到13．81±1．38和24．22±2．88（均P〈0．01）。15d后直到实验结束,MHC表达又下降到最初用药前水平。结论环孢素能-过性增加宿主MHCI类和MHCⅡ类的表达。

Influence of cyclosporine A on the mRNA and protein expression of major histocompatibility complexes I and II: experiment with rabbits

OBJECTIVE: To investigate the influence of cyclosporine A (CsA) on the mRNA and protein expression of major histocompatibility (MHC) I and II. METHODS: 14 New Zealand white rabbits were randomly divided into three groups to be injected intramuscularly 5 mg/kg once a day for 30 days (low dose CsA group, n = 5), 20 mg/kg (high dose CsA group, n = 5), or normal saline (control group, n = 4). Peripheral blood sample was collected every 5 days, monouclear cells were isolated, total RNA was extracted, and 30 days later the rabbits were killed and their livers, spleens, kidneys, and thyroid glands were taken out, total RNA was extracted, RT-PCR and Western blotting were used to examine the mRNA and protein expression of MHCI and MHCII. RESULTS: The peripheral blood monouclear cell MHCI and MHCII mRNA expression levels on day 10 of the low dose CsA group were 1.78 +/- 0.15 and 7.30 +/- 0.51, both significantly higher than those before the injection of CsA (0.23 +/- 0.04 and 2.77 +/- 0.25, both P < 0.01); the MHCI and MHCII protein expression levels were 11.32 +/- 1.45 and 22.31 +/- 1.91, both significantly higher than those before the injection (2.31 +/- 0.14 and 12.52 +/- 1.23, both P < 0.01). In high dose CsA group, the MHCI and MHCII mRNA expression levels on day 10 were 4.72 +/- 0.28 and 14.20 +/- 2.58, both significantly higher than those before the injection (0.24 +/- 0.06 and 2.56 +/- 0.33, both P < 0.01); the protein expression levels were 13.81 +/- 1.38 and 24.22 +/- 2.88, both significantly higher than those before the injection (2.42 +/- 0.06 and 12.51 +/- 1.31, both P < 0.01). Since the day 15, the levels of MHCI and MHCII mRNA and protein expression levels began decrease gradually until the levels before the injection. By the end of the experiment there was no significant difference in the MHCI and MHCII mRNA and protein expression levels of the liver, spleen, kidney, and thymus among the 3 groups. CONCLUSION: Cyclosporine can increase the host MHCI and MHCII expression for a period of time.