超声造影对糖尿病兔肾脏血流灌注的实验研究
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摘要
目的:以血肌酐、尿素氮、病理检查作为参照,应用实时超声造影技术结合时间-强度曲线定量评价糖尿病兔早期不同阶段肾皮质血流灌注特点及变化规律。
     方法:健康雄性成年家兔40只,随机分为正常对照组、糖尿病组,将四氧嘧啶按100mg/kg体重由耳缘静脉快速注射入糖尿病组体内,建立糖尿病兔模型;对照组注射生理盐水,之后自由进食水。分别于3天、1周、2周、4周、6周、8周、10周、12周抽取对照组和糖尿病组兔血化验血肌酐、尿素氮;然后在实时造影条件(机械指数0.088)下进行超声造影观察双侧肾脏血流灌注模式并储存造影动态图像,造影完毕,随机处死一只兔,摘取肾脏行病理检查,最后应用仪器内置的时间-强度量化分析软件对肾皮质血流灌注进行定量分析,量化参数包括达峰时间、曲线上升斜率、峰值强度、曲线下面积以及峰值强度减半时间等。以血生化指标及病理结果作为参照,与对照组比较,观察糖尿病兔早期不同阶段肾皮质的血流灌注变化情况。
     结果:糖尿病组兔注射四氧嘧啶后肾皮质血流灌注增大,1周、2周表现为时间-强度曲线参数中峰值强度升高、曲线下面积增大、达峰时间缩短、曲线上升斜率升高,此时病理可见肾小球肥大,系膜基质正常,基底膜无增厚;4周、6周,峰值强度、曲线下面积高于对照组,达峰时间、曲线上升斜率接近正常,系膜细胞增多。8周、10周、12周,达峰时间延长、曲线上升斜率减慢、峰值强度减半时间延长,病理出现肾小球系膜细胞明显增多,系膜基质增生,基底膜增厚,至12周病理出现部分毛细血管管腔闭塞,肾小球节段性硬化,峰值强度测值减低。对照组与糖尿病组各时间点血肌酐、尿素氮测值比较差异均无统计学意义。
     结论:
     1.超声造影定量分析可早期发现糖尿病肾血流灌注异常。
     2.糖尿病兔肾血流灌注的变化早于常规血生化改变。
     3.在糖尿病肾病发生、发展过程中,超声造影各参数变化与病理变化密切相关。
Objective: To access the characteristic and changes of the renal perfusion of diabetic rabbits at different stages by real-time contrast-enhanced ultrasound with time-intensity curve.
     Methods: 40 adult male rabbits were divided into control group and diabetes group at random. The models of diabetes were established by intravenously injecting alloxan, with sodium chloride for the control group. Scr and BUN were examined at 3d, 1w, 2w, 4w, 6w, 8w, 10w and 12w post-injection respectively for every group Real-time contrast-enhanced ultrasound were performed on bilateral kidney to observe the renal perfusion of both kidneys. After that, one rabbit was sacrificed randomly at each time point and its kidney was sampled for pathological examination. Renal perfusion was analyzed quantitatively with the time-intensity curve. The parameters of the time intensity curve included time to peak intensity (PIT), ascending slope rate of the curve, peak signal intensity (PSI), area under the curve (AUC) and time to half of peak intensity (HPT). Reference to the pathology and blood biochemistry, the study investigated the changes of blood perfusion and time-intensity curve parameters in diabetes rabbits at different stages.
     Results: The renal perfusion was increased in diabetes group after the injection of alloxan. The PSI, AUC and ascending slope rate of the curve of the time-intensity curve were increased in 1w and 2w with decreased of HPT; the pathological examination exhibited glomeruli hypertrophy and no thickening of basal lamina. The PSI and AUC in 4w and 6w were more than that of control group; the PIT and ascending slope rate of the curve got closed to normal in 4w and 6w; the intercapillary cells increased. The speed of ascending slope rate of the curve in 8w, 10w and 12w was slower, shown as PIT and HPT delayed; the pathological examination showned increasing of mesangial cell, hyperplasia of mesangial matrix and thickening of basal lamina, followed with obliteration of partial micrangium, glomerular sclerosis and reduce of PSI in 12w. Analysed the Scr and BUN in two groups, there was no significant difference.
     Conclusions:
     1. Contrast-enhanced ultrasound combined with time-intensity curve can analyze renal perfusion of diabetes quantitatively.
     2. The changes of renal perfusion in diabetic rabbits were earlier than that of blood biochemistry.
     3. The parameters’changes of contrast-enhanced ultrasound were closely related with pathology in diabetic nephropathy.
引文
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