【摘要】：目的本次研究借助評(píng)估T_2WI和動(dòng)態(tài)增強(qiáng)MRI(dynamic contrast enhanced magnetic resonance imaging,DCE-MRI)下單側(cè)腎動(dòng)態(tài)參數(shù)的縱向變化,探討線粒體靶向抗氧化劑Mito Q對(duì)大鼠腎臟缺血再灌注損傷(ischemia-reperfusion injury,IRI)的保護(hù)作用。方法本次研究得到天津醫(yī)科大學(xué)總醫(yī)院動(dòng)物保護(hù)和使用委員會(huì)的批準(zhǔn),并嚴(yán)格遵守實(shí)驗(yàn)室動(dòng)物保護(hù)和使用準(zhǔn)則。平均體重為250 g的雄性SD大鼠(北京大學(xué)醫(yī)學(xué)部育種中心)共計(jì)20只隨機(jī)分為四組:組I(IRI+Mito Q,n=5),大鼠在熱缺血開始前15 min以20 u L/s的速度通過鼠尾靜脈注射Mito Q(每只大鼠2.8mg/kg的劑量溶于700μL 0.9%的生理鹽水中)(澳新生物制藥公司捐贈(zèng)),然后夾閉左腎動(dòng)脈45 min,時(shí)間結(jié)束后取下金屬夾實(shí)現(xiàn)再灌注;組II(IRI+生理鹽水,n=5),與組I過程相似,除了通過鼠尾靜脈注射的是700μL 0.9%的生理鹽水;組III(正常大鼠+Mito Q,n=5),與組I過程相似,除了沒有進(jìn)行IRI操作;組IV(正常大鼠+生理鹽水,n=5),與組II過程相似,除了沒有進(jìn)行IRI操作。在術(shù)前(第0天)和術(shù)后(第2、5、7、14天)在3T MRI掃描儀上進(jìn)行大鼠腎臟掃描。分別量化雙腎外髓外帶(the outer stripe of the outer medulla,OSOM)的T2加權(quán)標(biāo)準(zhǔn)信號(hào)強(qiáng)度(T2-weighted standardized signal intensity,SSI)。采集大鼠腎臟多期DCE-MRI圖像,借助數(shù)學(xué)公式和時(shí)間-信號(hào)強(qiáng)度曲線(the time-intensity curve,TIC)分別量化雙腎濾過速率常數(shù)k_(cl),它代表了對(duì)比劑Gd-DTPA從皮質(zhì)濾過到髓質(zhì)。最后一次MRI檢查結(jié)束后處死所有大鼠,取下雙腎做組織病理學(xué)評(píng)分。用Kolmogorov Smirnov test檢驗(yàn)數(shù)據(jù)的正態(tài)性,用Levene's test檢驗(yàn)數(shù)據(jù)的方差齊性。不同時(shí)間點(diǎn)不同組別之間SSI和k_(cl)結(jié)果的差異用最小顯著差法評(píng)估。借助Kruskal-Wallis H檢驗(yàn)和Mann-Whitney U檢驗(yàn)比較不同腎臟組織病理學(xué)評(píng)分之間的差異。結(jié)果1.IRI大鼠OSOM的SSI高于對(duì)側(cè)腎,在術(shù)后第5天和第7天組I大鼠左腎OSOM的SSI低于組II大鼠左腎(術(shù)后第5天組I和組II,4.10±0.64,4.95±0.59,P=0.004;術(shù)后第7天組I和組II,4.78±0.97,6.40±0.94,P0.001)。2.IRI大鼠k_(cl)低于對(duì)側(cè)腎,術(shù)后不同時(shí)間點(diǎn)組I大鼠左腎k_(cl)高于組II大鼠左腎(術(shù)后第2天組I和組II,1.64±0.24,1.29±0.15,P=0.002;術(shù)后第5天組I和組II,1.92±0.18,1.22±0.28,P0.001;術(shù)后第7天組I和組II,2.07±0.29,1.60±0.30,P=0.001;術(shù)后第14天組I和組II,2.19±0.24,1.64±0.28,P0.001)。3.腎臟組織病理學(xué)分析表明腎損傷最嚴(yán)重的區(qū)域發(fā)生在組II中IRI腎臟OSOM,其組織病理學(xué)損傷評(píng)分高于組I中IRI腎臟(P0.001),其它腎臟組織學(xué)基本無變化。結(jié)論T_2WI表明腎臟缺血再灌注損傷主要發(fā)生在腎臟外髓外帶,其它各解剖帶損傷不大;SSI和k_(cl)結(jié)果證實(shí)腎臟缺血再灌注損傷的存在、k_(cl)證實(shí)線粒體靶向抗氧化劑Mito Q可降低腎缺血再灌注損傷,以上這些現(xiàn)象均可被腎臟組織病理學(xué)分析證實(shí)。
[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 鹵0.644.95 鹵0.59P0.004, II,4.10 鹵0.644.95 鹵0.59p 0.004; 7 days after operation, I and II,4.78 鹵0.976.40 鹵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 鹵0.241.29 鹵0.15 P0. 002 on the 2nd day after operation; II,1.92 鹵0. 1822 鹵0. 28P0. 001 in group I on the 5th day after operation; II,2.07 鹵0. 291.60 鹵0. 30P0. 001 in group I on the 7th day after operation; and II,2.19 鹵0. 241.64 鹵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.
【學(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R692;R445.2

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