超声造影技术定量分析兔慢性肾病血流灌注的实验研究

Expermental study on renal perfusion of chronic renal nephropathy in rabbits with contrast-enhanced ultrasound

目的探讨超声造影技术对兔慢性肾病肾纤维化评估的应用价值。方法将38只健康的新西兰兔随机分为空白对照组(6只)和实验组(32只)。实验组每日连续耳缘静脉注射阳离子牛血清白蛋白(C-BSA),诱导兔慢性肾病模型。在注射C-BSA后2、4、6、8周,采用超声造影技术检测兔肾皮质微循环灌注,与对照组进行比较;随后将兔处死,观察肾小球硬化及肾间质纤维化的病理学变化,分析超声参数与病理改变之间的相关性。结果 (1)超声造影参数结果显示:自注射C-BSA后6周起,峰值强度(DPI)明显降低,达峰时间(TTP)、平均渡越时间(MTT)与对照组比较明显延长,差异有统计学意义(P<0.01);至第8周,DPI及TTP进一步改变,与对照组比较,差异有统计学意义[(26.96±2.34)db vs(35.04±1.62)db,P<0.05;(24.31±1.82)svs(18.64±1.15)s,P<0.01)]。(2)肾脏纤维化各指标结果显示:注射C-BSA 4、6、8周后,肾小球硬化指数、肾间质胶原纤维面积增高,与对照组相比较,差异有统计学意义(0.81±0.36、1.43±0.25、2.15±0.30 vs 0.13±0.07;14.29%±4.62%、26.28%±10.09%、42.37%±10.41%vs1.21%±0.15%,均P<0.01),且纤维化随病程进展,逐渐增高。(3)相关分析显示:TTP与肾小球硬化指数、肾间质胶原纤维面积呈正相关(r=0.866、0.785,均P<0.01);DPI与肾小球硬化指数、肾间质胶原纤维面积呈负相关(r=-0.724、-0.739,均P<0.01)。结论超声造影定量分析技术可无创、客观检测兔慢性肾病肾皮质硬度和微循环灌注的变化。TTP与肾纤维化病理指标呈正相关,DPI与肾纤维化病理指标呈负相关,提示超声造影技术均可成为评价慢性肾病肾纤维化的重要方法之一。

Objective To explore the correlation of contrast-enhanced ultrasound （CEUS） parameters and the pathologic parameter of renal fibrosis. Methods Thirty-eight healthy New Zealand rabbits were randomly divided into the blank control group and the experimental group. The rabbits model was built by intravenous injection of C-bovine serum albumin （C-BSA） to rabbits of the experimental group. According to the different time points （2, 4, 6 and 8 weeks） after the injection of C-BSA, the rabbits in experimental group were randomly divided into 4 sub groups, 8 in each group. We collected the data of the CEUS parameters in the control group and the experimental group. Moreover, the renal tissues of the rabbits underwent pathologic examinations. Then, correlation analysis of CEUS parameters with parameters of renal fibrosis was performed. Results Dynamic changes of CEUS parameters： Renal cortical perfusion reduced from 6 weeks after the injection, manifested as the time to peak （TTP） and mean transit time （MTT） of the experimental group were longer than those of control group and the derived peak intensity （DPI） of the experimental group was lower than that of control group （P 〈 0.05 respectively）. The DPI and TTP at 8 weeks after the injection of the experimental group was significantly lower than those of the control group [（26.96±.2.34） db vs （35.04±1.62） db, P〈 0.05; （24.31±1.82） s vs （18.64±1.15） s, P〈 0.01]. Changes of each renal fibrosis parameter： we found that the results of the glomerulosclerosis indexes of the experimental group （4 weeks, 6 weeks and 8 weeks after the injection） were significantly higher than those of the control group （0.81±0.36, 1.43±0.25 and 2.15±0.30 vs 0.13±0.07, all P〈0.01）. The tubular interstitial collagen deposition scores of the experimental group （4 weeks, 6 weeks and 8 weeks after the injection） were significantly higher than those of the control group （14.29%±4.62%, 26.28%± 10.09% and 42.37%±10.41% vs 1.21%±0.15%, all P〈 0.01）. As the disease progressed, the results of each parameter increased. Pearson correlation analysis showed that the TTP of renal cortex was positively correlated with the glomerulosclerosis index and tubular interstitial collagen deposition score （r=-0.866 and 0.785, both P〈 0.01）. The DPI of renal cortex was negatively correlated with the glomerulosclerosis index and tubular interstitial collagen deposition score （r=-0.724 and -0.739, both P〈0.01）. Conclusions The results showed that CEUS could evaluate microcirculation perfusion of renal cortex. There is a positive association between TTP and fibrosis index. There is a negative association between DPI and fibrosis index. Thus, CEUS is an important method to evaluate the renal fibrosis in chronic renal nephropathy.