扩散张量成像早期诊断大鼠慢性移植物肾病及监测移植肾纤维化程度的价值

The value of diffusion tensor imaging in early diagnosis of chronic allograft nephropathy and monitoring graft fibrosis in rats

目的探讨扩散张量成像（DTI）早期诊断大鼠慢性移植物肾病（CAN）及监测移植肾纤维化程度的价值。 方法实验组以Fisher大鼠为供体、Lewis大鼠为受体，建立大鼠CAN模型30只；对照组以Lewis大鼠为供、受体建立原位同基因肾移植模型30只。所有大鼠移植术后14 d开始每2周检测1次肌酐浓度。采用数字表法随机选取各组大鼠8只分别于术后4、12、20周行连续性MRI检查，分别测量各组移植肾皮、髓质的ADC和部分各项异性（FA）值。从各组剩余的22只大鼠中分别于术后4、12、20周采用数字表法随机选取6只大鼠获取移植肾标本行病理分析，采用慢性移植物损伤指数（CADI）评分对各组移植肾标本进行评估，并定量检测α-平滑肌肌动蛋白（α-SMA）及波形蛋白（Vimentin）在移植肾组织中的表达。实验组和对照组间术后不同时间的肌酐值、皮质和髓质DTI参数值、CADI评分、α-SMA、Vimentin蛋白表达量的比较采用两独立样本t检验，实验组间CADI评分、α-SMA及Vimentin蛋白表达量的差异采用单因素方差分析比较。采用Pearson法评价实验组DTI参数与CADI评分、α-SMA、Vimentin蛋白表达量的相关性。 结果术后实验组大鼠肌酐持续升高，对照组大鼠肌酐无明显升高，术后第8周开始2组大鼠的肌酐差异有统计学意义（P均〈0.01）。T2WI像示对照组大鼠在术后不同时间点移植肾大小及信号强弱、分布无明显变化。实验组术后第4周与同期对照组相比，移植肾稍有增大，皮髓质信号较高，肾脏皮髓质分界不清，随术后时间的延长发生形态学及信号的变化，皮髓质信号逐渐增强，信号分布紊乱，分界更加模糊。术后第4、12、20周，实验组移植肾皮、髓质ADC和FA值较同期对照组均下降，差异均有统计学意义（P均〈0.05）；随着术后时间的延长，实验组移植肾皮、髓质ADC和FA值逐渐降低，而对照组移植肾皮、髓质参数值并未出现显著下降趋势。实验组皮质ADC、髓质ADC、皮质FA、髓质FA值与CADI评分、α-SMA和Vimentin蛋白表达量均呈负相关，r值为－0.50~－0.85，P均〈0.01。 结论DTI可早期诊断CAN并监测移植肾纤维化程度的改变。

ObjectiveTo estimate the value of diffusion tensor imaging （DTI） in early diagnosis of chronic allograft nephropathy （CAN） and monitoring of graft fibrosis in rat models. MethodsThirty CAN rat models were established as experimental group by transplanting Fisher donor kidneys into Lewis recipients. Thirty Lewis rats that received Lewis kidneys served as control group. Serum creatinine （SCr） was monitored regularly every two weeks from 14 days after transplantation. Eight rats were randomly selected by random number table method and underwent DTI examination at 4, 12, 20 weeks after modeling. DTI scans were performed on the renal cortex and medulla to measure apparent diffusion coefficient （ADC） and fractional anisotropy （FA）. From the remaining 22 rats in each group, 6 rats were randomly selected and underwent pathological analysis at 4, 12, 20 weeks after modeling. Histological changes in the kidney were evaluated by chronic allograft damage index （CADI） scores. The expression of alpha-smooth muscle actin （α-SMA） and Vimentin were quantitatively measured. The differences in creatinine, DTI parameters, CADI score, α-SMA, Vimentin expression level were analyzed by two independent samples t test in two groups, the differences among CADI score, α-SMA, Vimentin expression level of the experimental group were compared using ANOVA. The correlations among DTI parameters and CADI score, α-SMA and Vimentin expression level were analyzed using Pearson analysis. ResultsThe creatinine in the experimental group increased continuously, and the creatinine in the control group showed no significant increase. The difference in creatinine between the two groups was statistically significant from 8th week after operation （P〈0.01）. There was no obvious difference in the size and signal intensity of transplanted kidneys in control group at different time points. Compared with the control group, the graft kidney in the experimental group at the 4 weeks demonstrated increased signal intensity with mild increased volume of kidney, and the boundaries between cortex and medulla were not clear. The cortex and medulla showed gradually increased signal intensity, heterogeneous signal distribution and marginal haziness over time. The ADC and FA value of renal cortex and medulla in experimental group were significantly lower than those in control group at 4, 12, 20 weeks （P〈0.05）. The ADC and FA values of the cortex and medulla gradually decreased in the experimental group over time, while the values of the parameters in the control group did not show a significant decrease. The ADC and FA values of the cortex and medulla were negatively correlated with the scores of CADI, and the expression level of α-SMA, Vimentin in the experimental group（r=-0.50 to-0.85, P〈0.01）. ConclusionDTI can be an effective technique for early diagnosis of CAN and monitoring of graft fibrosis process.