借助T2WI和DCE-MRI评估Mito Q对大鼠肾脏缺血再灌注损伤的保护作用

发布时间：2018-10-15 20:38

【摘要】：目的本次研究借助评估T_2WI和动态增强MRI(dynamic contrast enhanced magnetic resonance imaging,DCE-MRI)下单侧肾动态参数的纵向变化,探讨线粒体靶向抗氧化剂Mito Q对大鼠肾脏缺血再灌注损伤(ischemia-reperfusion injury,IRI)的保护作用。方法本次研究得到天津医科大学总医院动物保护和使用委员会的批准,并严格遵守实验室动物保护和使用准则。平均体重为250 g的雄性SD大鼠(北京大学医学部育种中心)共计20只随机分为四组:组I(IRI+Mito Q,n=5),大鼠在热缺血开始前15 min以20 u L/s的速度通过鼠尾静脉注射Mito Q(每只大鼠2.8mg/kg的剂量溶于700μL 0.9%的生理盐水中)(澳新生物制药公司捐赠),然后夹闭左肾动脉45 min,时间结束后取下金属夹实现再灌注;组II(IRI+生理盐水,n=5),与组I过程相似,除了通过鼠尾静脉注射的是700μL 0.9%的生理盐水;组III(正常大鼠+Mito Q,n=5),与组I过程相似,除了没有进行IRI操作;组IV(正常大鼠+生理盐水,n=5),与组II过程相似,除了没有进行IRI操作。在术前(第0天)和术后(第2、5、7、14天)在3T MRI扫描仪上进行大鼠肾脏扫描。分别量化双肾外髓外带(the outer stripe of the outer medulla,OSOM)的T2加权标准信号强度(T2-weighted standardized signal intensity,SSI)。采集大鼠肾脏多期DCE-MRI图像,借助数学公式和时间-信号强度曲线(the time-intensity curve,TIC)分别量化双肾滤过速率常数k_(cl),它代表了对比剂Gd-DTPA从皮质滤过到髓质。最后一次MRI检查结束后处死所有大鼠,取下双肾做组织病理学评分。用Kolmogorov Smirnov test检验数据的正态性,用Levene's test检验数据的方差齐性。不同时间点不同组别之间SSI和k_(cl)结果的差异用最小显著差法评估。借助Kruskal-Wallis H检验和Mann-Whitney U检验比较不同肾脏组织病理学评分之间的差异。结果1.IRI大鼠OSOM的SSI高于对侧肾,在术后第5天和第7天组I大鼠左肾OSOM的SSI低于组II大鼠左肾(术后第5天组I和组II,4.10±0.64,4.95±0.59,P=0.004;术后第7天组I和组II,4.78±0.97,6.40±0.94,P0.001)。2.IRI大鼠k_(cl)低于对侧肾,术后不同时间点组I大鼠左肾k_(cl)高于组II大鼠左肾(术后第2天组I和组II,1.64±0.24,1.29±0.15,P=0.002;术后第5天组I和组II,1.92±0.18,1.22±0.28,P0.001;术后第7天组I和组II,2.07±0.29,1.60±0.30,P=0.001;术后第14天组I和组II,2.19±0.24,1.64±0.28,P0.001)。3.肾脏组织病理学分析表明肾损伤最严重的区域发生在组II中IRI肾脏OSOM,其组织病理学损伤评分高于组I中IRI肾脏(P0.001),其它肾脏组织学基本无变化。结论T_2WI表明肾脏缺血再灌注损伤主要发生在肾脏外髓外带,其它各解剖带损伤不大;SSI和k_(cl)结果证实肾脏缺血再灌注损伤的存在、k_(cl)证实线粒体靶向抗氧化剂Mito Q可降低肾缺血再灌注损伤,以上这些现象均可被肾脏组织病理学分析证实。
[Abstract]:Objective to investigate the protective effect of mitochondrial targeted antioxidant Mito Q on renal ischemia-reperfusion injury (ischemia-reperfusion injury,IRI) in rats by evaluating the longitudinal changes of unilateral renal dynamic parameters under T_2WI and dynamic enhanced MRI (dynamic contrast enhanced magnetic resonance imaging,DCE-MRI. Methods this study was approved by Animal Protection and use Committee of Tianjin Medical University General Hospital. A total of 20 male SD rats with an average weight of 250g (Peking University Medical Center for breeding) were randomly divided into four groups: group I (IRI Mito QN (5). The rats were injected with Mito Q (at a rate of 20 u L / s 15 min before the onset of hot ischemia through the tail vein of the rat. The dose of 2.8mg/kg was dissolved in 0.9% normal saline (700 渭 L) (donated by ANZ Biopharmaceutical Company), then the metal clip was removed after 45 min, clipping of left renal artery for reperfusion. The process of II (IRI in group I was similar to that in group I, except that 700 渭 L 0.9% saline was injected through tail vein of rats, and group III was similar to group I, except for no IRI operation. The process of IV in group A was similar to that in group II, except that IRI was not performed. Kidney scanning was performed on 3 T MRI scanner before operation (day 0) and postoperatively (day 2, 5, 7 and 14 days). The T 2 weighted standard signal intensity (T2-weighted standardized signal intensity,SSI) of extramedullary (the outer stripe of the outer medulla,OSOM was quantified respectively. The multiphase DCE-MRI images of rat kidney were collected, and the rate constant k _ (cl), of kidney filtration was quantified by mathematical formula and time-signal intensity curve (the time-intensity curve,TIC), which represented the contrast agent Gd-DTPA from cortical filtration to medulla. After the last MRI examination, all the rats were killed and the bilateral kidneys were taken out for histopathological score. The normality of data is tested by Kolmogorov Smirnov test and the homogeneity of variance is tested by Levene's test. The differences of SSI and (cl) results between different groups at different time points were evaluated by the least significant difference method. Kruskal-Wallis H test and Mann-Whitney U test were used to compare the differences between different renal histopathological scores. Results the SSI of OSOM in 1.IRI rats was higher than that in contralateral kidneys, and the SSI of left kidney OSOM in group I was lower than that in group II on the 5th and 7th day after operation (II,4.10 卤0.644.95 卤0.59P0.004, II,4.10 卤0.644.95 卤0.59p 0.004; 7 days after operation, I and II,4.78 卤0.976.40 卤0.94P0.001, respectively). The K _ (cl) of 2.IRI rats was lower than that of the contralateral kidneys. The K _ (cl) of left kidney in group I was higher than that in group II at different time points after operation (II,1.64 卤0.241.29 卤0.15 P0. 002 on the 2nd day after operation; II,1.92 卤0. 1822 卤0. 28P0. 001 in group I on the 5th day after operation; II,2.07 卤0. 291.60 卤0. 30P0. 001 in group I on the 7th day after operation; and II,2.19 卤0. 241.64 卤0. 28P0.001 in group I on the 14th day after operation). The histopathological analysis showed that the most serious area of renal injury occurred in IRI kidney OSOM, in group II. The histopathological injury score of IRI kidney was higher than that of IRI kidney in group I (P0. 001), but no change in other renal histology. Conclusion T_2WI showed that renal ischemia-reperfusion injury mainly occurred in the extramedullary zone of the kidney. The results of SSI and (cl) confirmed the existence of renal ischemia-reperfusion injury, and K _ (cl) confirmed that mitochondrial targeted antioxidant Mito Q could reduce renal ischemia-reperfusion injury. These phenomena can be confirmed by renal histopathological analysis.
【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R692;R445.2

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