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目的观察慢性移植物肾病(CAN)大鼠模型移植肾中C4d的沉积情况,并分析免疫抑制剂对C4d沉积的影响。方法将Fisher 344大鼠的肾移植到Lewis大鼠体内复制CAN模型,术后给予环孢素A(CsA)10 mg/(kg·d)×10 d。将模型鼠随机分为5组,每组9只,分别给予不同的药物:(1)生理盐水对照组;(2)CsA[6 mg/(kg·d)]组;(3)雷帕霉素[RAPA,0.8 mg/(kg·d)]组;(4)他克莫司[FK506,0.15 mg/(kg·d)]组;(5)霉酚酸[MMF,20 mg/(kg·d)]组。分别在术后第4、8及1 2周时处死每组大鼠3只,留取移植肾标本,根据Banff 97标准评价组织病理改变,用免疫荧光法检测C4d沉积情况。结果移植后第4周,各移植组中均未发现明显的CAN临床病理改变,各组Banff标准评分差异无统计学意义(P>0.05),但各组受体大鼠移植肾肾小管周围毛细血管(PTC)部位均出现C4d阳性沉积;术后8周各组均不同程度出现CAN的典型病理变化,PTC部位的C4d沉积增强;术后12周时CAN进展到最严重阶段,PTC部位的C4d沉积程度达到最大。C4d沉积与移植肾CAN病理改变呈正相关(r=0.894,P=0.000)。同对照组相比,CsA组和FK506组C4d沉积程度差异均无统计学意义(P>0.05),而MMF组和RAPA组能够减少C4d的沉积,差异有统计学意义(P<0.05)。结论大鼠肾移植后,PTC部位可出现C4d沉积,且产生的时间早于CAN发展的病理变化,同时C4d沉积的表达与CAN的进展相关。MMF和RAPA能够抑制CAN的进展,CsA和FK506无明显抑制作用。
Objective To observe the deposition of C4d in the graft kidney of rat model of chronic allograft nephropathy (CAN) and to analyze the effect of immunosuppressive agents on C4d deposition. Methods The kidney of Fisher 344 rats were transplanted into Lewis rats to replicate CAN model. CsA was given 10 mg / (kg · d) × 10 d after operation. The model rats were randomly divided into 5 groups with 9 rats in each group, which were given different drugs: (1) saline control group, (2) CsA [6 mg / (kg · d)] group, (4) tacrolimus [FK506 at 0.15 mg / (kg · d)]; (5) mycophenolic acid [MMF at 20 mg / (kg · D)] group. At the 4th, 8th and 12th week after surgery, 3 rats in each group were sacrificed, and the grafts of renal allografts were collected. The histopathological changes were evaluated according to Banff 97 standard. The deposition of C4d was detected by immunofluorescence. Results No obvious pathological changes of CAN were found in the 4th week after transplantation. There was no significant difference in Banff standard score among the three groups (P> 0.05), but the perirenal capillary C4dpositive deposition occurred in all the vessels (PTC). At 8 weeks after operation, typical pathological changes of CAN appeared in all groups, and C4d deposition in PTC increased. After 12 weeks, CAN progressed to the most serious stage. C4d The extent of deposition reached the maximum. There was a positive correlation between C4d deposition and CAN pathological changes (r = 0.894, P = 0.000). Compared with the control group, there was no significant difference in the C4d deposition between the CsA group and the FK506 group (P> 0.05), while the MMF group and the RAPA group could reduce the C4d deposition (P <0.05). Conclusions After the kidney transplantation in rats, C4d deposition may occur at PTC site, and the production of C4d is earlier than that of CAN. Meanwhile, the expression of C4d is correlated with the progression of CAN. MMF and RAPA can inhibit the progress of CAN, CsA and FK506 no significant inhibitory effect.