本文選題：急性腎損傷 + 兔�。� 參考：《安徽醫(yī)科大學(xué)》2017年碩士論文

【摘要】：背景:近年來急性腎損傷的發(fā)病率逐漸增高,給社會(huì)及家庭帶來了嚴(yán)重負(fù)擔(dān)。作為臨床上常見的危重癥,AKI主要表現(xiàn)為各種原因?qū)е碌亩虝r(shí)間內(nèi)的腎功能急劇下降,如少尿或無尿、體內(nèi)各種腎臟代謝廢物的積累、電解質(zhì)及體液平衡紊亂等,這些癥狀會(huì)引起消化、循環(huán)、血液等多系統(tǒng)損傷,給原發(fā)病的診療帶來極大的阻礙。AKI具有起病早、病程急、預(yù)后差的特點(diǎn),故早發(fā)現(xiàn)、早治療對(duì)該病的預(yù)后具有重要的意義。SCr及尿量作為目前AKI臨床診斷及分期的主要指標(biāo),易受到多種因素如藥物、尿路梗阻等影響,難以及時(shí)準(zhǔn)確提示AKI的發(fā)生,故其診斷AKI的可靠性不足。雖然近年來臨床上發(fā)現(xiàn)了多種新的檢驗(yàn)指標(biāo)如中性粒細(xì)胞明膠酶相關(guān)脂質(zhì)運(yùn)載蛋白(NGAL)、半胱氨酸蛋白酶抑制蛋白C(CysC)、白介素18(IL-18)、腎損傷因子1(KIM-1)等可以較敏感、早期的提示AKI的發(fā)生發(fā)展,但由于易受藥物代謝、年齡、體重等多種因素的影響,這些指標(biāo)的AKI診斷效能仍需要進(jìn)一步的研究確認(rèn)。超聲造影(CEUS)近年來在臨床上獲得了廣泛的應(yīng)用,與其他影像學(xué)檢查手段相比,CEUS所具備的各項(xiàng)優(yōu)點(diǎn)使其能夠客觀有效的評(píng)價(jià)腎臟微循環(huán)灌注程度,所使用的造影劑不經(jīng)腎臟代謝排出,無腎毒性,具有可重復(fù)性強(qiáng)、費(fèi)用低、可做床旁檢查、動(dòng)態(tài)顯示等優(yōu)點(diǎn),已有研究證實(shí)AKI的發(fā)生、發(fā)展及預(yù)后與腎臟微循環(huán)灌注的改變具有一定的聯(lián)系。應(yīng)用CEUS探討AKI時(shí)腎臟微循環(huán)灌注血流變化規(guī)律,可為AKI早期診療提供新的視角,而目前尚缺乏這方面的基礎(chǔ)研究,本研究的目的即在于此。目的:應(yīng)用CEUS探索順鉑所致兔AKI時(shí)腎臟血流微循環(huán)灌注的改變,探索早期AKI不同時(shí)間段時(shí)BUN、SCr與造影參數(shù)的變化規(guī)律,對(duì)BUN及SCr與超聲造影參數(shù)的關(guān)系進(jìn)行分析和探討,探討不同造影指標(biāo)對(duì)AKI的診斷效能和最佳診斷點(diǎn),并與常規(guī)指標(biāo)診斷效能進(jìn)行比較,在此基礎(chǔ)上結(jié)合腎臟病理檢查結(jié)果,評(píng)價(jià)CEUS在早期AKI診斷中的臨床應(yīng)用價(jià)值。方法:隨機(jī)選取雄性新西蘭大白兔40只,經(jīng)耳緣靜脈單次注射順鉑(5mg/kg)制作AKI模型,按照觀測(cè)時(shí)間點(diǎn)隨機(jī)分為6小時(shí)組(T6)、12小時(shí)組(T12),24小時(shí)組(T24),36小時(shí)組(T36)及48小時(shí)組(T48),每組8只,分別于建模前、后相應(yīng)時(shí)間點(diǎn)抽取耳緣靜脈血檢測(cè)BUN及SCr值,并進(jìn)行雙側(cè)腎臟CEUS檢查,使用Q-Lab軟件分析造影動(dòng)態(tài)圖像,獲取造影皮、髓質(zhì)定量參數(shù)RT,PI,WIS及AUC,使用SPSS22.0及MedCalc對(duì)數(shù)據(jù)進(jìn)行分析,以P0.05為差異具有統(tǒng)計(jì)學(xué)意義。以血清肌酐值較基線增高≥1.5倍作為AKI診斷金標(biāo)準(zhǔn),納入所有兔皮、髓質(zhì)造影定量參數(shù),繪制ROC曲線,獲取并比較各指標(biāo)的診斷效能和最佳截?cái)帱c(diǎn)。將各造影指標(biāo)截?cái)帱c(diǎn)標(biāo)準(zhǔn)與血肌酐標(biāo)準(zhǔn)的診斷效能進(jìn)行對(duì)比。實(shí)驗(yàn)結(jié)束后處死兔,取雙側(cè)腎臟,行常規(guī)石蠟包埋切片及蘇木精-伊紅(HE)染色,鏡下觀察改變。結(jié)果:建模后各組實(shí)驗(yàn)兔BUN及SCr均發(fā)生明顯的升高,T24、T36及T48組實(shí)驗(yàn)兔均發(fā)生AKI,BUN、SCr及HE染色鏡下觀察發(fā)現(xiàn)隨著建模時(shí)間增加,AKI呈進(jìn)行性加重。建模后T12、T24、T36及T48組皮質(zhì)RT,T24、T36及T48組皮質(zhì)PI,T36及T48組皮質(zhì)WIS、AUC較建模前具有顯著差異(P0.05)。與建模前相比,建模后髓質(zhì)各造影參數(shù)無明顯改變(P0.05)。皮質(zhì)造影參數(shù)RT較常規(guī)血清學(xué)指標(biāo)更早提示了AKI的發(fā)生。ROC曲線分析結(jié)果顯示:皮、髓質(zhì)造影指標(biāo)對(duì)AKI的診斷效能分別為較好、一般。皮、髓質(zhì)造影指標(biāo)內(nèi)部之間相比無明顯差異,皮質(zhì)WIS的診斷效能優(yōu)于髓質(zhì)WIS及RT,皮質(zhì)PI及AUC的診斷效能優(yōu)于髓質(zhì)AUC。與血肌酐標(biāo)準(zhǔn)相比較,皮質(zhì)RT截?cái)帱c(diǎn)標(biāo)準(zhǔn)的診斷效能較為優(yōu)異。結(jié)論:順鉑所致兔AKI在48小時(shí)內(nèi)呈進(jìn)行性加重,CEUS能夠敏感的反應(yīng)不同損傷程度下腎臟微循環(huán)灌注的改變,皮質(zhì)RT能夠比生化指標(biāo)較早的提示AKI的發(fā)生發(fā)展,皮、髓質(zhì)造影指標(biāo)均具有一定的AKI診斷效能,皮質(zhì)RT的診斷效能優(yōu)于常規(guī)血清肌酐檢查。
[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.

【學(xué)位授予單位】：安徽醫(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)】：R692.5;R445.1

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9 李U，

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