本文選題：多器官功能障礙綜合征 + 腎損傷��； 參考：《吉林大學(xué)》2016年博士論文

【摘要】：目的:危重病人特別是合并嚴(yán)重感染、缺血-再灌注損傷及中毒者,極易出現(xiàn)多器官功能障礙綜合征(Multiple Organ Dysfunction Syndromes,MODS),其中腎臟是最易受影響的器官之一。MODS發(fā)生腎損傷時(shí),其繼發(fā)的嚴(yán)重水電解質(zhì)酸堿平衡代謝紊亂,可使病情進(jìn)展迅速,導(dǎo)致病死率明顯增加。水通道蛋白(aquaporin,AQP)是水和尿素跨膜主動(dòng)轉(zhuǎn)運(yùn)機(jī)制的結(jié)構(gòu)基礎(chǔ),為監(jiān)測(cè)腎功能的動(dòng)態(tài)變化及早期干預(yù)治療腎損傷提供了新的靶點(diǎn)。水通道蛋白2(aquaporin 2,AQP2)在腎臟表達(dá),通過加壓素(Vasopressin,AVP)對(duì)集合管水通透性進(jìn)行調(diào)節(jié),在腎臟水代謝中發(fā)揮了重要的作用。AQP2異常表達(dá)可導(dǎo)致多種先天性或后天性腎臟疾病。腎臟鈉-鉀-三磷酸腺苷酶(Na~+-K~+-ATPase),又稱鈉鉀泵,鑲嵌在腎小管細(xì)胞膜的脂質(zhì)雙分子層中,除對(duì)鈉、鉀離子有轉(zhuǎn)運(yùn)功能外,還可以分解ATP使之釋放能量,并利用此能量進(jìn)行鈉、鉀的主動(dòng)轉(zhuǎn)運(yùn),其功能異常與疾病的嚴(yán)重程度呈正相關(guān),其功能的恢復(fù)先于疾病的好轉(zhuǎn),這對(duì)病情及預(yù)后的判斷有重要意義。本實(shí)驗(yàn)通過研究脂多糖及百草枯致多器官功能障礙大鼠模型炎癥介質(zhì)、腎臟AQP2及Na~+-K~+-ATPase的表達(dá)特點(diǎn),從炎癥反應(yīng)、腎小管功能及能量代謝方面研究腎損傷的可能發(fā)病機(jī)制。材料與方法:1.采用大鼠腹腔注射脂多糖(Lipopolysaccharide,LPS)5mg/kg或百草枯20mg/kg灌胃復(fù)制多器官功能障礙急性腎損傷動(dòng)物模型,同時(shí)應(yīng)用20mg/kg賴氨酸阿司匹林分別干預(yù)LPS和百草枯MODS模型。2.免疫組織化學(xué)染色測(cè)定腎臟AQP2蛋白表達(dá)。3.RT-PCR測(cè)定腎臟AQP2m RNA表達(dá)。4.常規(guī)病理切片HE染色進(jìn)行腎臟形態(tài)學(xué)檢查。5.Na~+-K~+-ATPase試劑盒測(cè)定腎小管上皮細(xì)胞Na~+-K~+-ATPase含量及活性。6.ELSIA法測(cè)定百草枯大鼠外周血IL-1,IL-10,TNF-ɑ細(xì)胞因子表達(dá)及流式細(xì)胞儀測(cè)定外周血淋巴細(xì)胞凋亡比率。結(jié)果:1.LPS組大鼠肌酐、尿素氮水平逐漸增高,在48小時(shí)達(dá)高峰,此后逐漸降低;LPS組大鼠尿量早期(12h,24h)逐漸減少,此后明顯增多。百草枯組大鼠肌酐、尿素氮水平逐漸增高,尿量無明顯減少。2.LPS組大鼠腎臟病理切片可見明顯的腎小管上皮細(xì)胞腫脹,腎小管管腔變小;腎小球腫脹,炎癥細(xì)胞浸潤(rùn);部分腎小管細(xì)胞壞死。百草枯組大鼠腎小管上皮細(xì)胞腫脹明顯,但細(xì)胞壞死很少。3.LPS組大鼠腎小管上皮細(xì)胞AQP2m RNA表達(dá)在6h時(shí)增高,隨后迅速降低,在2d降至最低,爾后逐漸增高。百草枯組大鼠腎小管上皮細(xì)胞AQP2m RNA表達(dá)表達(dá)明顯降低,在2~3d時(shí)達(dá)最低水平,賴氨酸阿司匹林則可以減輕這種改變。4.LPS組大鼠腎臟組織在實(shí)驗(yàn)12h出現(xiàn)腎小管上皮細(xì)胞AQP2蛋白表達(dá)減少,在2d腎臟AQP2蛋白表達(dá)減少最為明顯,此后逐漸增加;百草枯組大鼠腎小管上皮細(xì)胞AQP2蛋白表達(dá)在24h后明顯降低,在2~3d時(shí)達(dá)最低水平,賴氨酸阿司匹林則可以減輕這種改變。5.各組大鼠Na~+-K~+-ATP酶含量無明顯差異;但LPS及百草枯組大鼠Na~+-K~+-ATP酶活性在造模成功后明顯降低,此后逐漸增高,但仍低于對(duì)照組,賴氨酸阿司匹林則可減輕這種改變。6.百草枯中毒組大鼠淋巴細(xì)胞凋亡比率明顯增高,而賴氨酸阿司匹林可以減輕百草枯中毒導(dǎo)致的淋巴細(xì)胞凋亡。百草枯組TNF-ɑ、IL-1、IL-10表達(dá)明顯增加,賴氨酸阿司匹林可以抑制TNF-ɑ、IL-1的表達(dá)增加,但促進(jìn)IL-10的表達(dá)增加。結(jié)論:1.LPS致多器官功能障礙綜合征大鼠尿素氮、肌酐增高,APQ2表達(dá)明顯減少,腎小管上皮細(xì)胞腫脹、功能障礙甚至凋亡與炎癥反應(yīng)有關(guān)。2.LPS致多器官功能障礙綜合征腎功能恢復(fù)階段,尿量的多少與AQP2的表達(dá)呈負(fù)相關(guān)。AQP2是腎臟重吸收功能恢復(fù)的結(jié)構(gòu)基礎(chǔ),Na~+-K~+-ATPase是腎臟功能恢復(fù)的能量代謝基礎(chǔ),Na~+-K~+-ATPase通過直接參與及間接調(diào)控的方式提示腎臟的能量代謝狀態(tài),只有在AQP2蛋白表達(dá)及能量代謝狀態(tài)接近正常水平后受損的腎臟功能才逐漸好轉(zhuǎn)。3.早期應(yīng)用賴氨酸阿司匹林可通過抑制炎癥反應(yīng)的機(jī)制改善LPS致MODS腎損傷的預(yù)后。4.百草枯可引起全身炎癥反應(yīng)及多器官功能障礙,但這些表現(xiàn)較LPS引起者是延遲出現(xiàn)的,提示百草枯導(dǎo)致的MODS并非毒物直接引起的,而是由過度的炎癥反應(yīng)導(dǎo)致的。5.無論是炎癥反應(yīng)直接導(dǎo)致的MODS還是百草枯通過炎癥反應(yīng)間接引起的MODS,均可通過應(yīng)用賴氨酸阿司匹林阻斷或減輕炎癥反應(yīng)的途徑,對(duì)受損的靶器官起到保護(hù)作用。
[Abstract]:Objective: critically ill patients, especially with severe infection, ischemic reperfusion injury and poisoning, are extremely susceptible to Multiple Organ Dysfunction Syndromes (MODS), in which the kidney is one of the most susceptible organs, one of the most vulnerable organs,.MODS with renal injury, and the secondary severe acid-base metabolic disorder of electrolyte acid-base metabolism, which can make it possible Aquaporin (AQP) is the structural basis for the active transmembrane mechanism of water and urea, which provides a new target for monitoring the dynamic changes of renal function and early intervention in the treatment of renal injury. The expression of aquaporin 2 (aquaporin 2, AQP2) in the kidney, through the vasopressin (Vasopressin, AVP) Regulating the water permeability of the collection tube and playing an important role in the water metabolism of the kidney, the abnormal expression of.AQP2 can lead to a variety of congenital or acquired renal diseases. The renal sodium potassium triphosphate ATPase (Na~+-K~+-ATPase), also known as the sodium potassium pump, is embedded in the lipid bilayer of the renal tubular cell membrane, with the exception of the sodium and potassium ions. In addition, it can also decompose ATP to release energy, and use this energy to carry on the active transport of sodium and potassium. The dysfunction of the disease is positively related to the severity of the disease. The recovery of its function is preceded by the improvement of the disease, which is of great significance to the judgement of the condition and prognosis. Rat model inflammatory mediators, renal AQP2 and Na~+-K~+-ATPase expression characteristics, from inflammatory response, renal tubule function and energy metabolism to study the possible pathogenesis of renal injury. Materials and methods: 1. rat intraperitoneal injection of lipopolysaccharide (Lipopolysaccharide, LPS) 5mg/kg or paraquat 20mg/kg replicating multiple organ dysfunction acute kidney Damage animal models and 20mg/kg lysine aspirin interfered with LPS and paraquat MODS model respectively,.2. immunohistochemical staining was used to determine the expression of renal AQP2 protein,.3.RT-PCR, AQP2m RNA, AQP2m RNA,.4. routine pathological section, HE staining, HE staining, renal morphological examination,.5.Na~+-K~ +-ATPase kit for renal tubular epithelial cells ~+-K~+-ATPase content and active.6.ELSIA method were used to determine IL-1, IL-10, TNF- cytokine expression and flow cytometry for peripheral blood lymphocyte apoptosis ratio in peripheral blood of paraquat rats. Results: the level of creatinine and urea nitrogen increased gradually in the 1.LPS group, reached the peak at 48 hours, and gradually decreased after this, and the early urine volume in the LPS group (12h, 24h) gradually increased. The level of creatinine and urea nitrogen in the paraquat group increased gradually, and the urine volume did not decrease obviously in the kidney pathological sections of the.2.LPS group. The renal tubular epithelial cells were swelling, the renal tubule cavity became smaller, glomerular swelling, inflammatory cells infiltrated, and some renal tubular cells were necrotic. The renal tubule epithelium of paraquat group was fine. The cell swelling was obvious, but the expression of AQP2m RNA in the renal tubular epithelial cells in the.3.LPS group was higher, then decreased rapidly, and then decreased to the lowest in 2D, and then gradually increased. The expression of AQP2m RNA in the renal tubular epithelial cells of the paraquat group decreased significantly, and the lowest level was at 2~3d, and lysine aspirin could reduce this. The expression of AQP2 protein in renal tubular epithelial cells decreased in experimental 12h and the expression of AQP2 protein in 2D kidney decreased most obviously, and then increased gradually. The expression of AQP2 protein in renal tubular epithelial cells in paraquat group decreased significantly after 24h and the lowest level in 2~3d, and lysine aspirin could decrease. There was no significant difference in the Na~+-K~+-ATP enzyme content of.5. rats in each group, but the activity of Na~+-K~+-ATP enzyme in LPS and paraquat rats decreased obviously after the mold making, and then gradually increased, but still lower than that of the control group. Lysine aspirin could reduce the rate of lymphocyte apoptosis in the.6. paraquat group. Lysine aspirin can reduce the apoptosis of lymphocyte caused by paraquat poisoning. The expression of TNF-, IL-1 and IL-10 in paraquat group is significantly increased. Lysine aspirin can inhibit the expression of TNF-, increase the expression of IL-1, but increase the expression of IL-10. Conclusion: the expression of urea nitrogen, creatinine, APQ2 expression in multiple organ dysfunction syndrome rats induced by 1.LPS Significantly decreased, renal tubular epithelial cells swelling, dysfunction or even apoptosis related to the inflammatory response to.2.LPS induced renal function recovery phase of multiple organ dysfunction syndrome, the amount of urine is negatively related to the expression of AQP2.AQP2 is the structural basis for the recovery of renal reabsorption function, Na~+-K ~+-ATPase is the basis of energy metabolism of renal function recovery. Na~+-K~+-ATPase indicates the energy metabolic state of the kidney through direct participation and indirect regulation. Only after the expression of AQP2 protein and the state of energy metabolism are near the normal level, the impaired renal function is gradually improved. The early application of lysine aspirin can improve the preconditioning of LPS induced MODS renal injury by inhibiting the mechanism of inflammation. The post.4. paraquat can cause systemic inflammatory response and multiple organ dysfunction, but these manifestations are delayed than those caused by LPS, suggesting that the MODS caused by paraquat is not a direct cause of the poison, but is caused by excessive inflammatory response, whether the MODS or paraquat directly caused by the inflammatory reaction, or by the inflammatory reaction. MODS can protect the damaged target organs by using lysine aspirin to block or reduce the inflammatory response.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類號(hào)】：R459.7

【相似文獻(xiàn)】

相關(guān)期刊論文 前10條

1 高根五;多器官功能障礙綜合征[J];醫(yī)師進(jìn)修雜志;2000年08期

2 傅貴峰,陳偉,羅瑛,丁杰;急性呼吸窘迫綜合征合并多器官功能障礙21例分析[J];安徽醫(yī)學(xué);2000年01期

3 何海武;多器官功能障礙綜合征21例分析[J];海南醫(yī)學(xué);2000年05期

4 郭寶平,何炳威,錢東翔,蔡哲鵬,王智堅(jiān),郭煒;中樞神經(jīng)系統(tǒng)疾病并發(fā)多器官功能障礙綜合征的臨床救治[J];中華急診醫(yī)學(xué)雜志;2002年01期

5 吳廣禮,王麗暉,楊新軍,劉宇,黃旭東,張萬里,汪晶華;老年人多器官功能障礙綜合征救治成功一例[J];中華老年醫(yī)學(xué)雜志;2003年01期

6 張英海,楊婷,劉偉新;老年病人術(shù)后多器官功能障礙綜合征32例防治體會(huì)[J];中國老年學(xué)雜志;2005年05期

7 王永進(jìn),王澤惠,侯云生;復(fù)蘇后多器官功能障礙綜合征[J];中國急救醫(yī)學(xué);2005年07期

8 任新生;;多器官功能障礙綜合征與臟器功能支持[J];中華急診醫(yī)學(xué)雜志;2006年04期

9 王龍;;58例多器官功能障礙綜合征臨床分析[J];海南醫(yī)學(xué);2006年07期

10 于振英;;妊娠合并多器官功能障礙綜合征14例分析[J];中國中西醫(yī)結(jié)合急救雜志;2006年03期

相關(guān)會(huì)議論文 前10條

1 岳茂興;;多器官功能障礙及衰竭的臨床救治新策略[A];第三屆全國急診創(chuàng)傷學(xué)學(xué)術(shù)交流會(huì)論文匯編[C];1999年

2 賀文奇;;影響多器官功能障礙綜合征患者臨床及預(yù)后因素的綜合分析[A];全國危重病急救醫(yī)學(xué)學(xué)術(shù)會(huì)議論文匯編[C];2007年

3 羅紅濤;龍輝;葉一農(nóng);劉全妹;林小清;嚴(yán)海明;;分子吸附再循環(huán)系統(tǒng)治療多器官功能障礙綜合征觀察[A];第三屆全國重型肝病及人工肝血液凈化學(xué)術(shù)年會(huì)論文集（上冊(cè)）[C];2007年

4 鐘志越;;多器官功能障礙綜合征發(fā)病機(jī)制德研究進(jìn)展[A];2008全國中西醫(yī)結(jié)合危重病、急救醫(yī)學(xué)學(xué)術(shù)會(huì)議學(xué)術(shù)論文集[C];2008年

5 李大亮;唐國生;蔣勁柏;劉建;李大蔚;;恙蟲病并多器官功能障礙35例臨床分析[A];中華醫(yī)學(xué)會(huì)第五次全國重癥醫(yī)學(xué)大會(huì)論文匯編[C];2011年

6 方如美;周刊;徐建明;陸恩峰;羅仕云;;7例5000米越野軍訓(xùn)導(dǎo)致多器官功能障礙分析[A];第十一屆全國中西醫(yī)結(jié)合腎臟病學(xué)術(shù)會(huì)議論文匯編[C];2010年

7 任成山;;多器官功能障礙綜合征的概念和發(fā)病機(jī)制[A];2000年全國危重病急救醫(yī)學(xué)學(xué)術(shù)會(huì)議論文集[C];2000年

8 涂勝豪;陸付耳;李鳴真;;中西醫(yī)結(jié)合治療多器官功能障礙綜合征的思考[A];2001年全國中西醫(yī)結(jié)合急救醫(yī)學(xué)學(xué)術(shù)會(huì)議論文集[C];2001年

9 霍開秀;謝建雄;涂昌弟;李復(fù)雄;王曉川;周秀紅;;多器官功能障礙綜合征患者氧利用率的變化與預(yù)后關(guān)系[A];中華醫(yī)學(xué)會(huì)急診分會(huì)第五屆全國危重病學(xué)術(shù)交流會(huì)論文匯編[C];2004年

10 韓愛玲;袁劍萍;;66例多器官功能障礙綜合征臨床分析[A];中華醫(yī)學(xué)會(huì)急診醫(yī)學(xué)分會(huì)第十次全國復(fù)蘇中毒學(xué)術(shù)論文交流會(huì)論文匯編[C];2004年

相關(guān)重要報(bào)紙文章 前3條

1 張獻(xiàn)懷 雷永升;多器官功能障礙研究有重大進(jìn)展[N];光明日?qǐng)?bào);2001年

2 ;全身感染與多器官功能障礙綜合征的臨床與基礎(chǔ)研究[N];中國醫(yī)藥報(bào);2003年

3 齊文中;中毒性多器官功能障礙診斷有新標(biāo)[N];山西經(jīng)濟(jì)日?qǐng)?bào);2000年

相關(guān)博士學(xué)位論文 前10條

1 王恒進(jìn);生物人工腎的優(yōu)化構(gòu)建及其治療多器官功能障礙綜合征的作用及機(jī)制研究[D];南京中醫(yī)藥大學(xué);2015年

2 尹永杰;多器官功能障礙綜合征急性腎損傷水通道蛋白2的表達(dá)[D];吉林大學(xué);2016年

3 陳繼紅;連續(xù)性血液透析濾過對(duì)多器官功能障礙犬器官功能和細(xì)胞因子的影響及作用機(jī)制研究[D];新疆醫(yī)科大學(xué);2008年

4 吳建國;自體移植凍存豬骨髓內(nèi)皮祖細(xì)胞防治多器官功能障礙的研究[D];第二軍醫(yī)大學(xué);2011年

5 曹衛(wèi)紅;腸道部分缺血再灌注損傷致多器官功能障礙動(dòng)物模型和發(fā)病機(jī)理的研究[D];中國人民解放軍軍醫(yī)進(jìn)修學(xué)院;2004年

6 羅天航;自體移植內(nèi)皮祖細(xì)胞防治多器官功能障礙的研究[D];第二軍醫(yī)大學(xué);2008年

7 李南;復(fù)蘇后多器官功能障礙家兔模型臟器功能損傷機(jī)制的研究[D];吉林大學(xué);2011年

8 李菲;泛素化對(duì)多器官功能障礙綜合征脾臟樹突狀細(xì)胞功能的調(diào)節(jié)作用與機(jī)制研究[D];中國人民解放軍軍事醫(yī)學(xué)科學(xué)院;2012年

9 劉茜;多器官功能障礙綜合征小鼠脾臟耐受性樹突狀細(xì)胞及其負(fù)向免疫調(diào)節(jié)作用的研究[D];中國人民解放軍軍事醫(yī)學(xué)科學(xué)院;2010年

10 毛慧娟;新型血液凈化方式治療多器官功能障礙綜合征及其對(duì)免疫功能影響的實(shí)驗(yàn)和臨床研究[D];南京醫(yī)科大學(xué);2009年

相關(guān)碩士學(xué)位論文 前10條

1 樸藝花;多器官功能障礙綜合征回顧性分析及預(yù)后相關(guān)因素研究[D];延邊大學(xué);2012年

2 達(dá)·霹莉情;多器官功能障礙綜合征患者的凝血功能變化及其意義[D];新疆醫(yī)科大學(xué);2013年

3 布合力其·麥麥提;連續(xù)性血液透析濾過對(duì)多器官功能障礙犬單核細(xì)胞凋亡的影響[D];新疆醫(yī)科大學(xué);2011年

4 金福順;多器官功能障礙綜合征的臨床回顧性分析[D];延邊大學(xué);2011年

5 侯云峰;多器官功能障礙綜合征患者血清熱休克蛋白70的變化及其臨床意義[D];山東大學(xué);2012年

6 陳豆豆;氨基胍對(duì)酵母多糖誘發(fā)小鼠多器官功能障礙綜合征的影響[D];廣西醫(yī)科大學(xué);2006年

7 王仁海;連續(xù)性血液透析濾過對(duì)多器官功能障礙犬器官功能的影響[D];新疆醫(yī)科大學(xué);2008年

8 李巖;多器官功能障礙綜合征時(shí)血管內(nèi)皮細(xì)胞損傷的研究[D];新疆醫(yī)科大學(xué);2009年

9 王志方;血必凈在嚴(yán)重外傷并發(fā)多器官功能障礙綜合征應(yīng)用中的評(píng)價(jià)[D];大連醫(yī)科大學(xué);2013年

10 黃海燕;59例多器官功能障礙綜合征的死因分析[D];廣州中醫(yī)藥大學(xué);2014年

，

本文編號(hào)：2043080