本文選題：腎缺血再灌注損傷 + Nesfatin-1��； 參考：《武漢大學(xué)》2016年博士論文

【摘要】：背景：腎臟缺血再灌注損傷(Renal ischemia reperfusion injury, RIRI)在泌尿外科領(lǐng)域的臨床工作中是一種常見的病理生理過程,是腎移植術(shù)、腎部分切除術(shù)、腎組織楔形切除術(shù)、腎盂腎實(shí)質(zhì)聯(lián)合切開取石術(shù)、失血性休克及主動(dòng)脈修補(bǔ)術(shù)等疾病所共同遭受的一個(gè)多種因素和環(huán)節(jié)參與的病理過程。腎臟組織的血流灌注非常豐富,且對(duì)缺血再灌注損傷很敏感,如果手術(shù)中腎臟組織缺血時(shí)間過長(zhǎng),它不僅可引起急性腎小管壞死,造成急性腎功能衰竭的重要因素之一,同時(shí)也是腎移植術(shù)后腎功能異常及影響患者腎功能的恢復(fù)的重要原因。相關(guān)的研究表明,腎IRI是影響腎移植術(shù)后腎組織存活時(shí)間的危險(xiǎn)因素。由腎缺血再灌注損傷所引發(fā)的相關(guān)疾病的發(fā)病率和死亡率持續(xù)增高,因此,如何有效的干預(yù)腎IRI引起的腎功能損害及腎功能的保護(hù)越來越多的受到關(guān)注,在泌尿外科領(lǐng)域中仍然是一個(gè)值得探究的重要問題。腎IRI的發(fā)病機(jī)理錯(cuò)綜復(fù)雜,目前尚未完全闡明,目前的研究資料表明,腎缺血再灌注損傷的病理生理機(jī)制可能與氧自由基的大量產(chǎn)生、炎癥介質(zhì)反應(yīng)、Ca2+超載及細(xì)胞凋亡等相關(guān)。Nesfatin-1是一種下丘腦分泌的神經(jīng)多肽類物質(zhì),在能量平衡和代謝過程中發(fā)揮著十分重要的作用。研究證實(shí),nesfatin-1具有多種生化和生理功能,在不同的人體疾病和動(dòng)物模型中參與了各種病理生理過程�，F(xiàn)有的研究表明,nesfatin-1現(xiàn)已應(yīng)用于心肌缺血再灌注損傷、腸缺血再灌注損傷、胃粘膜損傷、蛛網(wǎng)膜下腔出血性損傷及創(chuàng)傷性腦損傷的動(dòng)物模型中,具有一定的保護(hù)作用。但目前尚未見nesfatin-1防治腎IRI的相關(guān)報(bào)道。因此,我們推測(cè)nesfatin-1可能在大鼠的腎缺血再灌注損傷中具有保護(hù)作用。本課題擬探究nesfatin-1預(yù)處理對(duì)大鼠腎缺血再灌注損傷有無保護(hù)作用和其相關(guān)的可能機(jī)制進(jìn)行初步的研究。目的：以nesfatin-1為研究對(duì)象,評(píng)估n esfatin-1對(duì)大鼠腎缺血再灌注損傷的影響并探索其可能的作用機(jī)制。方法：體重為200-250g的雄性Wistar大鼠24只,隨機(jī)分成三組,即偽手術(shù)組(Sham組或正常對(duì)照組)、腎缺血再灌注組(I/R組)、腎缺血再灌注組+nesfatin-1預(yù)處理組。每組的大鼠各為8只。腎I/R組及腎I/R+ nesfatin-1預(yù)處理組的大鼠通過采用右腎切除加微型無創(chuàng)傷性動(dòng)脈夾夾閉左側(cè)腎蒂的方法建立大鼠腎缺血再灌注模型。第一部分：檢測(cè)nesfatin-1預(yù)處理后對(duì)腎功能(BUN、Scr)的影響,通過HE和PAS染色觀察腎臟組織的病理形態(tài)學(xué)變化；第二部分：通過檢測(cè)超氧化物歧化酶(SOD)、丙二醛(MDA)、過氧化氫酶(CAT)及還原型谷胱甘肽(GSH)量的變化評(píng)估iesfatin-1預(yù)處理對(duì)腎缺血再灌注損傷在氧化應(yīng)激方面的作用；第三部分：通過檢測(cè)TUNEL、Caspase-3、Bcl2 及 Bax的表達(dá)量的變化評(píng)價(jià)nesfatin-1預(yù)處理對(duì)腎缺血再灌注損傷在凋亡方面的影響；第四部分：通過檢測(cè)髓過氧化物酶(MPO)、TNF-α、IL-1β、IL-6 及 NF-κB的表達(dá)情況,以評(píng)價(jià)nesfatin-1預(yù)處理對(duì)腎缺血再灌注損傷在炎癥方面的影響。結(jié)果：1、腎功能檢測(cè)結(jié)果顯示,與腎I/R組相比較,I/R+nesfatin-1組的尿素氮(BUN)和肌酐(Scr)水平顯著低于腎I/R組(P0.05),表明nesfatin-1預(yù)處理具有一定保護(hù)腎功能的作用。2、光鏡下檢測(cè)發(fā)現(xiàn),與腎I/R組相比較,I/R+nesfatin-1組的組織形態(tài)學(xué)變化明顯減輕,病理學(xué)評(píng)分明顯降低(P0.01),表明nesfatin-1預(yù)處理可以減輕腎IRI所導(dǎo)致的腎臟組織的形態(tài)學(xué)損傷。3、氧化應(yīng)激途徑的影響：結(jié)果顯示,與腎I/R組相比較,I/R+nesftin-1組的SOD、CAT、GSH的活性明顯增加(P0.01),而MDA的水平顯著降低(P0.01),表明了經(jīng)nesftin-1預(yù)處理后氧自由基清除酶SOD、CAT、GSH的活性增加,使腎IRI時(shí)增多的氧自由基清除增加,從而使增加的氧自由基水平降低,最終使其介導(dǎo)生成的MDA表達(dá)水平減少。4、凋亡方面的影響：與腎I/R組相比較,I/R+nesftin-1組的TUNEL凋亡表達(dá)數(shù)目顯著降低(P0.05),進(jìn)一步通過比較Caspase-3、Bcl2、Bax的表達(dá)量及Bcl2/Bax的比值發(fā)現(xiàn),：/R+nesftin-1組的Caspase-3和Bax的表達(dá)顯著降低(P0.01),Bcl2的表達(dá)量顯著增高(P0.01),Bcl2/Bax之比顯著增加(P0.05),說明I/R+nesftin-1組的細(xì)胞凋亡降低,表明nesftin-1預(yù)處理可以在腎缺血再灌注損傷中減少凋亡細(xì)胞的發(fā)生。5、炎癥方面的影響：結(jié)果顯示,I/R+nesftin-1組的MPO、TNF-α、IL-1β、IL-6及NF-κB的表達(dá)量顯著降低,表明nesfatin-1預(yù)處理能夠在腎缺血再灌注損傷中減少炎癥反應(yīng)的發(fā)生。結(jié)論：1、在大鼠的腎缺血再灌注損傷中,Nesfatin-1預(yù)處理具有腎功能的保護(hù)作用,并能減輕腎臟組織的形態(tài)學(xué)損傷。2、Nesfatin-1預(yù)處理對(duì)腎缺血再灌注損傷的腎臟組織具有顯著的抗氧化作用。3、Nesfatin-1預(yù)處理對(duì)腎缺血再灌注損傷具有明顯的抗凋亡效應(yīng),其作用可能是通過抑制細(xì)胞凋亡及上調(diào)抗凋亡基因表達(dá)的路徑而實(shí)現(xiàn)的。4、Nesfatin-1預(yù)處理在腎缺血再灌注損傷中抑制了炎癥反應(yīng)的中性粒細(xì)胞的活化,并抑制炎性因子的釋放,從而減輕了炎癥反應(yīng),對(duì)大鼠的腎IRI發(fā)揮腎臟保護(hù)作用。
[Abstract]:Background: Renal ischemia reperfusion injury (RIRI) is a common pathophysiological process in the clinical work in the field of Department of urology. It is a renal transplantation, partial nephrectomy, renal tissue wedge resection, renal pelvis renal parenchyma incision and stone removal, hemorrhagic shock and aortic repair. The renal tissue is very rich in blood flow and is very sensitive to ischemia reperfusion injury. If the time of renal tissue ischemia is too long during the operation, it can not only cause acute renal tubular necrosis, but also one of the important factors of acute renal failure, and it is also a kidney transplant. Abnormality of postoperative renal function and important reasons for the recovery of renal function in patients. Related studies have shown that renal IRI is a risk factor affecting the survival time of renal tissue after renal transplantation. The incidence and mortality of related diseases caused by renal ischemia-reperfusion injury continue to increase, and how to effectively interfere with renal function caused by renal IRI More and more attention has been paid to the protection of damage and renal function, which is still an important issue in the field of Department of urology. The pathogenesis of renal IRI is complicated and is not fully elucidated. The present research data show that the pathogenesis of renal ischemia reperfusion injury may be associated with a large number of oxygen free radicals and inflammation. .Nesfatin-1 is a neuropolypeptide secreted by the hypothalamus, which is a neuropeptide secreted by the hypothalamus. It plays a very important role in the process of energy balance and metabolism. It has been proved that nesfatin-1 has many biochemical and physiological functions and has been involved in various pathophysiology in different human diseases and animal models. Process. Existing studies have shown that nesfatin-1 has been applied to myocardial ischemia reperfusion injury, intestinal ischemia-reperfusion injury, gastric mucosal injury, subarachnoid hemorrhage injury and traumatic brain injury in animal models, but there is no related report on the prevention and treatment of renal IRI by nesfatin-1. Therefore, we speculate that NES Fatin-1 may play a protective role in renal ischemia-reperfusion injury in rats. This subject is to explore the protective effect of nesfatin-1 preconditioning on renal ischemia reperfusion injury in rats and its possible mechanism. Objective: To evaluate the effect of n esfatin-1 on renal ischemia-reperfusion injury in rats by using nesfatin-1 as the research object. Influence and explore its possible mechanism of action. Methods: 24 male Wistar rats weighing 200-250g were randomly divided into three groups, namely, pseudo operation group (Sham group or normal control group), renal ischemia reperfusion group (group I/R) and +nesfatin-1 preconditioning group of renal ischemia reperfusion group. Each group was 8 rats each. Kidney I/R group and kidney I/R+ nesfatin-1 preconditioning group. Rat model of renal ischemia reperfusion was established by using right nephrectomy and mini traumatic artery clamp to clamp the left renal pedicle. Part 1: the effects of nesfatin-1 preconditioning on renal function (BUN, Scr) were detected, and the morphological changes of renal tissue were observed by HE and PAS staining. The second part: by detecting SUPEROXYGEN Changes in SOD, MDA, catalase (CAT) and reduced glutathione (GSH); the role of iesfatin-1 preconditioning on oxidative stress in renal ischemia reperfusion injury; third part: evaluation of the expression of TUNEL, Caspase-3, Bcl2 and Bax by the evaluation of nesfatin-1 preconditioning for renal ischemia and reperfusion The effect of perfusion injury on apoptosis; Fourth: by detecting the expression of myeloperoxidase (MPO), TNF- alpha, IL-1 beta, IL-6 and NF- kappa B in order to evaluate the effect of nesfatin-1 preconditioning on renal ischemia reperfusion injury in inflammation. Results: 1, renal function test results showed that the urine of the renal I/R group was compared with the kidney I/R group and the urine of the I/R+nesfatin-1 group. The level of BUN and creatinine (Scr) was significantly lower than that of the renal I/R group (P0.05), which showed that nesfatin-1 preconditioning had a certain role in protecting the renal function.2. Under the light microscope, the histologic changes of the I/R+nesfatin-1 group were obviously reduced and the pathological score was significantly reduced (P0.01), indicating that nesfatin-1 preconditioning could reduce the IR renal function. The morphological damage of renal tissue caused by I was.3, the effect of oxidative stress pathway. The results showed that the activity of SOD, CAT, GSH in the group I/R+nesftin-1 was significantly increased (P0.01) compared with the I/R group of the kidney (P0.01), and the level of MDA decreased significantly (P0.01). The increase of oxygen free radical scavenging increased the increased oxygen free radical level, and finally reduced the level of MDA expression by.4 and apoptosis. Compared with group I/R, the number of TUNEL apoptotic expression in group I/R+nesftin-1 decreased significantly (P0.05), and the expression of Caspase-3, Bcl2, Bax and Bcl2/Bax were compared. The expression of Caspase-3 and Bax in the:/R+nesftin-1 group was significantly decreased (P0.01), the expression of Bcl2 increased significantly (P0.01), and the ratio of Bcl2/Bax increased significantly (P0.05), indicating that the apoptosis in the I/R+nesftin-1 group decreased, indicating that nesftin-1 pretreatment could reduce the incidence of apoptotic cells in the renal hemorrhage reperfusion injury. Results: the results showed that the expression of MPO, TNF- a, IL-1 beta, IL-6 and NF- kappa B in the I/R+nesftin-1 group decreased significantly, indicating that nesfatin-1 preconditioning could reduce the occurrence of inflammatory reaction in renal ischemia reperfusion injury. Conclusion: 1, in rats with renal ischemia reperfusion injury, Nesfatin-1 preconditioning has the protective effect of renal function and can be reduced. The morphological damage of renal tissue is.2, Nesfatin-1 preconditioning has a significant antioxidant effect on renal ischemia reperfusion injury.3. Nesfatin-1 preconditioning has obvious anti apoptosis effect on renal ischemia-reperfusion injury, and its effect may be achieved by inhibiting apoptosis and increasing the path of anti apoptotic gene expression. .4, Nesfatin-1 preconditioning inhibits the activation of neutrophils in the inflammatory response and inhibits the release of inflammatory factors in the renal ischemia-reperfusion injury, thus alleviates the inflammatory response and plays a renal protective role in the renal IRI of rats.
【學(xué)位授予單位】：武漢大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類號(hào)】：R692;R-332

【相似文獻(xiàn)】

相關(guān)期刊論文 前4條

1 鄧潤(rùn)鈞;田字彬;;Nesfatin-1的研究新進(jìn)展[J];胃腸病學(xué);2014年06期

2 許麗萍;成興波;魯燕;;血清Nesfatin-1水平與肥胖和2型糖尿病的相關(guān)性研究[J];中國(guó)糖尿病雜志;2012年05期

3 顧光大;;血清nesfatin-1在2型糖尿病合并冠心病中的診斷意義[J];心腦血管病防治;2014年02期

4 ;[J];;年期

相關(guān)會(huì)議論文 前2條

1 陳曦;蔣正堯;;大鼠下丘腦注射nesfatin-1調(diào)制葡萄糖敏感神經(jīng)元興奮性抑制攝食[A];中國(guó)生理學(xué)會(huì)第23屆全國(guó)會(huì)員代表大會(huì)暨生理學(xué)學(xué)術(shù)大會(huì)論文摘要文集[C];2010年

2 程亞穎;羅曉雷;;nesfatin-1在小與胎齡大鼠下丘腦的表達(dá)及意義[A];中華醫(yī)學(xué)會(huì)第十七次全國(guó)兒科學(xué)術(shù)大會(huì)論文匯編（下冊(cè)）[C];2012年

相關(guān)博士學(xué)位論文 前1條

1 蔣冠軍;Nesfatin-1預(yù)處理在大鼠腎缺血再灌注損傷模型中的保護(hù)作用及相關(guān)機(jī)制的研究[D];武漢大學(xué);2016年

相關(guān)碩士學(xué)位論文 前7條

1 張迪;中樞nesfatin-1通過交感神經(jīng)調(diào)節(jié)外周脂肪代謝[D];青島大學(xué);2015年

2 王曉蕾;Nesfatin-1對(duì)體外培養(yǎng)卵泡黃素化顆粒細(xì)胞分泌雌、孕激素的影響[D];濱州醫(yī)學(xué)院;2015年

3 宋文科;Nesfatin-1對(duì)大鼠腦干孤束核葡萄糖敏感神經(jīng)元電活動(dòng)的影響[D];青島大學(xué);2010年

4 王文杰;迷走復(fù)合體微量注射Nesfatin-1對(duì)攝食及葡萄糖敏感神經(jīng)元的作用[D];青島大學(xué);2010年

5 單芹;血清nesfatin-1與2型糖尿病的關(guān)系研究[D];青海大學(xué);2014年

6 王盼;血清nesfatin-1在妊娠、哺乳和甲狀腺功能異常所致攝食變化中的作用[D];青島大學(xué);2010年

7 張愛青;Nesfatin-1在人及嚙齒類動(dòng)物消化系統(tǒng)的表達(dá)[D];南京醫(yī)科大學(xué);2010年

，

本文編號(hào)：1997031