超声造影评价顺铂所致兔早期急性肾损伤的实验研究

发布时间：2018-04-28 12:07

本文选题：急性肾损伤 + 兔　；参考：《安徽医科大学》2017年硕士论文

【摘要】：背景:近年来急性肾损伤的发病率逐渐增高,给社会及家庭带来了严重负担。作为临床上常见的危重症,AKI主要表现为各种原因导致的短时间内的肾功能急剧下降,如少尿或无尿、体内各种肾脏代谢废物的积累、电解质及体液平衡紊乱等,这些症状会引起消化、循环、血液等多系统损伤,给原发病的诊疗带来极大的阻碍。AKI具有起病早、病程急、预后差的特点,故早发现、早治疗对该病的预后具有重要的意义。SCr及尿量作为目前AKI临床诊断及分期的主要指标,易受到多种因素如药物、尿路梗阻等影响,难以及时准确提示AKI的发生,故其诊断AKI的可靠性不足。虽然近年来临床上发现了多种新的检验指标如中性粒细胞明胶酶相关脂质运载蛋白(NGAL)、半胱氨酸蛋白酶抑制蛋白C(CysC)、白介素18(IL-18)、肾损伤因子1(KIM-1)等可以较敏感、早期的提示AKI的发生发展,但由于易受药物代谢、年龄、体重等多种因素的影响,这些指标的AKI诊断效能仍需要进一步的研究确认。超声造影(CEUS)近年来在临床上获得了广泛的应用,与其他影像学检查手段相比,CEUS所具备的各项优点使其能够客观有效的评价肾脏微循环灌注程度,所使用的造影剂不经肾脏代谢排出,无肾毒性,具有可重复性强、费用低、可做床旁检查、动态显示等优点,已有研究证实AKI的发生、发展及预后与肾脏微循环灌注的改变具有一定的联系。应用CEUS探讨AKI时肾脏微循环灌注血流变化规律,可为AKI早期诊疗提供新的视角,而目前尚缺乏这方面的基础研究,本研究的目的即在于此。目的:应用CEUS探索顺铂所致兔AKI时肾脏血流微循环灌注的改变,探索早期AKI不同时间段时BUN、SCr与造影参数的变化规律,对BUN及SCr与超声造影参数的关系进行分析和探讨,探讨不同造影指标对AKI的诊断效能和最佳诊断点,并与常规指标诊断效能进行比较,在此基础上结合肾脏病理检查结果,评价CEUS在早期AKI诊断中的临床应用价值。方法:随机选取雄性新西兰大白兔40只,经耳缘静脉单次注射顺铂(5mg/kg)制作AKI模型,按照观测时间点随机分为6小时组(T6)、12小时组(T12),24小时组(T24),36小时组(T36)及48小时组(T48),每组8只,分别于建模前、后相应时间点抽取耳缘静脉血检测BUN及SCr值,并进行双侧肾脏CEUS检查,使用Q-Lab软件分析造影动态图像,获取造影皮、髓质定量参数RT,PI,WIS及AUC,使用SPSS22.0及MedCalc对数据进行分析,以P0.05为差异具有统计学意义。以血清肌酐值较基线增高≥1.5倍作为AKI诊断金标准,纳入所有兔皮、髓质造影定量参数,绘制ROC曲线,获取并比较各指标的诊断效能和最佳截断点。将各造影指标截断点标准与血肌酐标准的诊断效能进行对比。实验结束后处死兔,取双侧肾脏,行常规石蜡包埋切片及苏木精-伊红(HE)染色,镜下观察改变。结果:建模后各组实验兔BUN及SCr均发生明显的升高,T24、T36及T48组实验兔均发生AKI,BUN、SCr及HE染色镜下观察发现随着建模时间增加,AKI呈进行性加重。建模后T12、T24、T36及T48组皮质RT,T24、T36及T48组皮质PI,T36及T48组皮质WIS、AUC较建模前具有显著差异(P0.05)。与建模前相比,建模后髓质各造影参数无明显改变(P0.05)。皮质造影参数RT较常规血清学指标更早提示了AKI的发生。ROC曲线分析结果显示:皮、髓质造影指标对AKI的诊断效能分别为较好、一般。皮、髓质造影指标内部之间相比无明显差异,皮质WIS的诊断效能优于髓质WIS及RT,皮质PI及AUC的诊断效能优于髓质AUC。与血肌酐标准相比较,皮质RT截断点标准的诊断效能较为优异。结论:顺铂所致兔AKI在48小时内呈进行性加重,CEUS能够敏感的反应不同损伤程度下肾脏微循环灌注的改变,皮质RT能够比生化指标较早的提示AKI的发生发展,皮、髓质造影指标均具有一定的AKI诊断效能,皮质RT的诊断效能优于常规血清肌酐检查。
[Abstract]:Background: the incidence of acute renal injury has increased in recent years, which has brought serious burdens on society and family. As a clinically common critical disease, AKI is mainly manifested in a sharp decline in renal function in a short period of time, such as oliguria or no urine, accumulation of various renal metabolic wastes in the body, electrolyte and body fluid balance disorder, etc. These symptoms can cause many systemic injuries such as digestive, circulatory and blood, which greatly hinders the diagnosis and treatment of the original disease..AKI has the characteristics of early onset, emergency course and poor prognosis. Therefore, early treatment has important significance for the prognosis of the disease..SCr and urine volume are the main indicators of the clinical diagnosis and staging of AKI, which are easily subject to a variety of factors. Such as drugs, urinary tract obstruction and so on, it is difficult to timely and accurate indication of the occurrence of AKI, so the reliability of the diagnosis of AKI is insufficient. Although several new tests have been found in bed in recent years, such as neutrophil gelatinase related lipid carrier protein (NGAL), cysteine protease inhibitor C (CysC), interleukin 18 (IL-18), renal injury factor 1 (KIM-) 1) it can be more sensitive, early hint of the development of AKI, but the AKI diagnostic efficiency of these indexes still needs further study due to the influence of many factors such as drug metabolism, age, weight and so on. Contrast ultrasound (CEUS) has been widely used in clinic in recent years, compared with other imaging methods, CEUS has All the advantages make it objective and effective to evaluate the degree of renal microcirculation perfusion. The contrast agent is not excreted by kidney metabolism, without renal toxicity. It has the advantages of strong repeatability, low cost, bedside examination, dynamic display and so on. It has been proved that the occurrence of AKI, the development and prognosis and the changes of renal microcirculation perfusion have a certain extent. The application of CEUS to explore the changes of renal microcirculation perfusion flow in AKI can provide a new perspective for the early diagnosis and treatment of AKI, but the basic research of this area is still lacking. The purpose of this study is to explore the changes of renal blood flow microcirculation in AKI induced by cisplatin in rabbit with CEUS, and to explore the different time periods of early AKI. The changes of BUN, SCr and contrast parameters, the relationship between BUN and SCr and the parameters of ultrasound contrast were analyzed and discussed. The diagnostic efficiency and the best diagnostic points of different contrast indexes on AKI were discussed, and compared with the conventional diagnostic efficacy. Based on the results of renal pathological examination, the clinical evaluation of CEUS in the early AKI diagnosis was evaluated. Methods: 40 male New Zealand white rabbits were randomly selected, and AKI model was made by single injection of cisplatin (5mg/kg) into the auricular vein. According to the observation time point, the AKI model was randomly divided into 6 hour group (T6), 12 hour group (T12), 24 hour group (T24), 36 hour group (T36) and 48 hour group (T48), 8 in each group, respectively, before the modeling and then the corresponding time point extraction ear edge respectively. Venous blood test BUN and SCr values, and bilateral renal CEUS examination, use Q-Lab software to analyze dynamic contrast images, obtain contrast skin, medulla quantitative parameters RT, PI, WIS and AUC, using SPSS22.0 and MedCalc to analyze the data with P0.05 difference. The serum creatinine value is more than 1.5 times greater than the baseline as a AKI diagnostic gold. The criteria were included in all rabbit skin, medullary imaging quantitative parameters, drawing ROC curve, obtaining and comparing the diagnostic efficiency and the best truncation point of each index. Compare the diagnostic efficacy of each index truncation point standard with the blood creatinine standard. After the experiment, rabbits were killed and bilateral kidney was taken, routine paraffin embedded section and hematoxylin eosin (HE) staining were performed. Results: the BUN and SCr of the rabbits in each group were significantly increased after modeling. The rabbits in T24, T36 and T48 groups were all AKI, BUN, SCr and HE staining mirrors found that the AKI showed progressive aggravation as the time of modeling increased. There was significant difference compared with that before modeling (P0.05). Compared with the model before modeling, there was no significant change in the medulla contrast parameters (P0.05). The corticography parameter RT earlier suggested the.ROC curve of AKI than the conventional serological index. The results showed that the skin, the medulla contrast index was better for the diagnostic efficiency of AKI, the skin, and the medullary contrast index. The diagnostic efficiency of cortical WIS was better than that of medulla WIS and RT, and the diagnostic efficiency of cortical PI and AUC was better than that of medulla AUC. and serum creatinine standard. The diagnostic efficacy of cortical RT truncation point was superior to that of cortical RT truncation point. Conclusion: the rabbit AKI caused by cisplatin was progressively aggravated within 48 hours, and CEUS can react differently to different damage. To the extent of renal microcirculation perfusion, cortical RT can suggest the occurrence and development of AKI earlier than the biochemical index, and the skin and medullary contrast indexes have a certain AKI diagnostic efficiency, and the diagnostic efficacy of cortical RT is better than that of normal serum creatinine.

【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R692.5;R445.1

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