超声造影定量分析家兔糖尿病早期肾血流灌注参数变化

目的应用实时超声造影技术定量评价家兔糖尿病早期不同阶段肾皮质血流灌注参数的变化.方法四氧嘧啶按每公斤体重100 mg经家兔耳缘静脉快速注射,成功建立家兔糖尿病模型组19只;正常对照组13只,注射等量0.9%氯化钠溶液.于成功建模后3 d、1周、2周、4周、6周、8周、10周、12周分别采用苦味酸法、尿素酶法检测家兔肌酐、尿素,随后对家兔行超声造影,定量分析双侧肾血流灌注,测量峰值强度(PSI)、达峰时间(PIT)、峰值强度减半时间(HPT)、曲线上升斜率(以K1表示)和曲线下面积(AUC),每次超声造影后随机处死家兔1只,取检肾脏组织进行病理学检查.结果成功建模后各时间点糖尿病组家兔肌酐、尿素生化测值与正常对照组家兔比较差异均无统计学意义,而糖尿病组家兔肾皮质血流灌注较正常对照组家兔增强.成功建模后3 d,糖尿病组家兔PSI、PIT、HPT、K1和AUC与对照组家兔比较差异均无统计学意义;成功建模后1周、2周,与正常对照组家兔比较,糖尿病组家兔PSI升高、PIT缩短、K1增大、AUC增大,且差异均有统计学意义(成功建模后1周:F值分别为24.087、37.309、15.586、43.629,P均<0.05;成功建模后2周:F值分别为30.146、118.009、9.228、38.200,P均<0.05),肾脏病理学检查仅可见肾小球肥大.成功建模后4周、6周,糖尿病组家兔PSI、AUC高于正常对照组家兔,且差异均有统计学意义(成功建模后4周:F值分别为15.470、12.335,P均<0.05;成功建模后6周:F值分别为7.532、11.757,P均<0.05),肾脏病理学检查示肾小球系膜细胞增多.成功建模后8周、10周、12周,与正常对照组家兔比较,糖尿病组家兔PSI降低、PIT延长、HPT延长、K1减小、AUC增大,且差异均有统计学意义(成功建模后8周:F值分别为6.821、7.964、50.309、6.744、12.905,P均<0.05或0.01;成功建模后10周:F 值分别为7.012、12.410、97.148、7.165、12.258,P均<0.05或0.01;成功建模后12周:F值分别为6.786、33.515、146.258、9.760、7.045,P均<0.05或0.01),肾脏病理学检查示肾小球系膜细胞明显增多,系膜基质增生,基底膜增厚,至成功建模后12周,肾脏病理学检查示部分肾小球毛细血管管腔闭塞,节段性硬化.正常对照组家兔PSI、PIT、HPT、K1、AUC在成功建模后3 d、1周、2周、4周、6周、8周、10周、12周不同时间点的差异均无统计学意义.结论糖尿病组家兔肾血流灌注超声造影参数的变化与病理改变有关,且早于常规血生化指标改变.

Quantitative analysis of the renal perfusion of diabetic rabbit by ultrasound contrast imaging

Objective To assess the changes of renal perfusion of diabetic rabbits at early stage of diabetes by contrast enhanced ultrasound(CEUS).Methods Nineteen diabetic rabbits were made successfully by injecting alloxan intravenously and isometric sodium chloride solution for control group of thirteen.CEUS was performed on bilateral kidney for evaluating renal perfusion at 3 d,1 week,2 weeks,4 weeks,6 weeks,8 weeks,10 weeks and 12 weeks.Creatinine and urea nitrogen were detected by creatinine-HR and urease method and pathological examinations were done at the same time before and after CEUS respectively.The parameters of CEUS included peak signal intensity(PSI),time to peak intensity(PIT),time to half of peak intensity(HPT),ascending slope rate of the curve(K1)and area under the curve(AUC).Results Creatinine and urea nitrogen were not significant among the different time in diabetic rabbits.The renal perfusion increased in diabetes group.PSI,K1 and AUC increased and PIT decreased at 1 week and 2 weeks(F=24.087,15.586,43.629 and 37.309,all P<0.05;F=30.146,9.228,38.200 and 118.009,all P<0.05),pathological examination exhibited glomeruli hypertrophy.PSI and AUC were greater than those of control group at 4 weeks and 6 weeks with intercapillary cells increasing confirmed by pathology(F=15.470 and 12.335,both P<0.05;F=7.532 and 11.757,both P<0.05).PSI reduced,PIT and HPT delayed,K1 decreased and AUC increased at 8 weeks,10 weeks and 12 weeks(F=6.821,7.964,50.309,6.744 and 12.905,all P<0.05 or 0.01;F=7.012,12.410,97.148,7.165 and 12.258,all P<0.05 or 0.01;F=6.786,33.515,146.258,9.760 and 7.045,all P<0.05 or 0.01),pathological examination showed increase of mesangial cell,hyperplasia of mesangial matrix and thickening of basal lamina,followed with obliteration of partial micrangium and glomerular sclerosis.The vascular occlusion and glomerular sclerosing segmental appeared after 12 w of the model established successfully.PSI,PIT,HPT,K1,AUC of nomal control group had no significant difference at 3 d,1 week,2 weeks,4 weeks,6 weeks,8 weeks,10 weeks and 12 weeks,respectively.Conclusions The changes of renal perfusion of early diabetes quantitatively analyzed by CEUS are earlier than those of creatinine and urea nitrogen and were in accordance with pathological changes.