本文選題：NF-E2-related + factor-2��； 參考：《武漢大學(xué)》2014年博士論文

【摘要】：背景： 腸缺血再灌注(Intestinal Ischemia Reperfusion, IIR)損傷是一種臨床創(chuàng)傷及休克時(shí)最為常見(jiàn)的病理生理機(jī)制。腸道因其特殊的細(xì)菌環(huán)境、特殊的結(jié)構(gòu)和代謝特點(diǎn)以及重要的屏障功能,亦是導(dǎo)致休克、創(chuàng)傷后重要臟器包括肺臟、腎臟和肝臟等遠(yuǎn)隔臟器損傷的“樞紐”,仍然是相關(guān)學(xué)科研究的熱點(diǎn)問(wèn)題。新近研究表明,Nrf2是一種調(diào)控細(xì)胞關(guān)鍵轉(zhuǎn)錄因子,其可以有效誘導(dǎo)細(xì)胞對(duì)抗氧化應(yīng)激損傷,是機(jī)體重要的內(nèi)源性保護(hù)機(jī)制,但其在腸缺血再灌注致腎損傷中的作用及機(jī)制尚待探討。傳統(tǒng)中藥人參的主要成分——人參皂苷Rbl由于具備“多靶效應(yīng)”的獨(dú)特優(yōu)勢(shì),特別是其抗氧化作用是減輕多臟器缺血再灌注損傷的重要機(jī)制。然而,目前極少關(guān)于人參皂苷Rbl對(duì)腸缺血再灌注致繼發(fā)性遠(yuǎn)隔臟器損傷保護(hù)作用具體機(jī)制的研究。因此,Nrf2/ARE信號(hào)通路作為機(jī)體重要的內(nèi)源性保護(hù)機(jī)制,對(duì)于其在腸缺血再灌注引起的遠(yuǎn)隔臟器損傷中的保護(hù)作用及機(jī)制亟待研究。 目的： 研究人參皂苷Rb1對(duì)腸缺血再灌注致小鼠急性腎損傷的影響,研究其對(duì)腎臟組織Nrf2表達(dá)的影響及保護(hù)機(jī)制。 方法： 1、隨機(jī)將成年雄性C57BL/6J小鼠分為5組：①假手術(shù)組(sham組)；②腸缺血再灌注組(IIR組)；③生理鹽水組(NS組)；④低劑量組(RB1-30組)；⑤高劑量組(RB1-60組)。采用夾閉腸系膜上動(dòng)脈法建立小鼠腸缺血再灌注模型,在光學(xué)顯微鏡下分別觀察小腸組織及腎臟組織的形態(tài)病理學(xué)改變,測(cè)定血清中DAO、BUN和Scr水平的變化,以及腎臟組織中MDA含量和SOD活性的改變。 2、隨機(jī)將成年雄性C57BL/6J小鼠分為6組：①假手術(shù)組(sham組)；②腸缺血再灌注+生理鹽水組(IIR組)；③腸缺血再灌注+人參皂苷Rbl組(RB1組)；④假手術(shù)+ATRA組(sham+ATRA組)；⑤腸缺血再灌注+生理鹽水+ATRA組(IIR+ATRA組)；⑥腸缺血再灌注+人參皂苷Rbl+ATRA組(RB1+ATRA組)。在光學(xué)顯微鏡下觀察腎臟組織的形態(tài)病理學(xué)改變,測(cè)定血清中BUN、Scr和NGAL水平的變化,和腎臟組織中MDA含量和SOD活性的改變,以及TUNEL細(xì)胞凋亡檢測(cè)和Bcl-2/Bax蛋白表達(dá)比值,免疫組化及Western blot檢測(cè)腎臟組織中Nrf2和HO-1蛋白含量的變化。 結(jié)果： 1、IIR組與NS組較sham組中的小腸和腎臟損傷程度顯著加劇,病理學(xué)評(píng)分明顯增高(P0.01)；血清DAO、BUN、Scr和腎臟組織MDA含量較sham組明顯升高(P0.01)；腎臟組織SOD活性較sham組明顯降低(P0.01)；IIR組與NS組各組數(shù)據(jù)之間均無(wú)統(tǒng)計(jì)學(xué)差異(P0.05)；與IIR組和NS組比較,RB1-30組和RB1-60組中腎臟損傷程度明顯減輕(P0.01),血清DAO、BUN和SCr水平、腎臟組織MDA含量明顯降低而SOD活性明顯升高(P0.01)。 2、RB1組中腎臟損傷程度較IIR組顯著降低(P0.01),血清BUN、Scr和NGAL、腎臟組織MDA含量較IIR組明顯降低(P0.01)；腎臟組織SOD活性較IIR組明顯升高(P0.01)；IIRN腎臟TUNEL凋亡細(xì)胞和Bcl-2/Bax蛋白表達(dá)比值較sham組明顯增加(P0.01)；RB1組腎臟TUNEL凋亡細(xì)胞和Bcl-2/Bax蛋白表達(dá)比值較IIR組明顯降低(P0.01)。IIR組中HO-1、Nrf2含量較sham組顯著增高(P0.01)；RB1組中HO-1、Nrf2含量較IIR組進(jìn)一步增高(P0.01)。sham+ATRA組與sham組、IIR+ATRA組與IIR組中各指標(biāo)均無(wú)統(tǒng)計(jì)學(xué)差異(P0.05)。而RB1+ATRA組較RB1組腎臟組織損傷程度顯著增高(P0.01)；腎臟組織MDA含量明顯升高(P0.01)；SOD活性明顯降低(P0.01)；腎臟TUNEL凋亡細(xì)胞和Bcl-2/Bax蛋白表達(dá)比值明顯升高(P0.01)；核內(nèi)Nrf2蛋白含量雖無(wú)顯著性差異(P0.05),但胞漿HO-1蛋白含量明顯減少(P0.01)。 結(jié)論： 小鼠腸缺血再灌注可導(dǎo)致急性腎臟損傷,人參皂苷Rbl后處理有效減輕腸缺血再灌注所致的腎臟細(xì)胞凋亡以及損傷程度,其機(jī)制可能與激活Nrf2/ARE信號(hào)通路及其下游信號(hào)分子相關(guān)。
[Abstract]:Background:
Intestinal Ischemia Reperfusion (IIR) injury is the most common pathophysiological mechanism of clinical trauma and shock. The intestinal tract, due to its special bacterial environment, special structural and metabolic characteristics, and important barrier function, is also a shock, and the important organs including the lungs, kidneys and liver after trauma. The "hub" of organ damage is still a hot issue in related subjects. Recent studies have shown that Nrf2 is a key factor in regulating cell key transcription factors, which can effectively induce cell resistance to oxidative stress damage and is an important endogenous protective mechanism in the body. However, the role and mechanism of it in the injury of kidney after intestinal ischemia-reperfusion still remain to be discussed. The main component of the traditional Chinese medicine ginseng, ginsenoside Rbl, has the unique advantage of "multi target effect", especially its antioxidant effect is an important mechanism to reduce the injury of multiple organ ischemia-reperfusion. However, few of the specific mechanisms of ginsenoside Rbl on the protective effect of intestinal ischemia-reperfusion on the protection of the secondary viscera injury by intestinal ischemia reperfusion Therefore, as an important endogenous protective mechanism of the body, the protective effect and mechanism of Nrf2/ARE signal pathway on the injury of distant viscera caused by intestinal ischemia-reperfusion need to be studied.
Objective:
Objective to study the effects of ginsenoside Rb1 on acute kidney injury induced by intestinal ischemia-reperfusion in mice, and to study the effect of Ginsenoside on Nrf2 expression in renal tissue and its protective mechanism.
Method錛，

本文編號(hào)：2026609