HMGB1在腎臟熱、冷缺血再灌注損傷中作用機(jī)理及干預(yù)研究
發(fā)布時(shí)間：2018-09-04 08:41
【摘要】：正文：尿毒癥為慢性腎功能不全的終末階段,在我國每年新發(fā)病率為0.01%,其中大多數(shù)為青壯年,嚴(yán)重影響了人們的健康和生命安全。腎移植是治療終末期腎病的最佳治療手段,可以顯著的提高終末期腎病患者的生活質(zhì)量,減少并發(fā)癥的發(fā)生,并降低終末期腎病的死亡率。雖然隨著移植手術(shù)技巧的改進(jìn),新型免疫抑制藥物的應(yīng)用,圍手術(shù)期并發(fā)癥及早期急性排斥反應(yīng)發(fā)生率明顯減低,大大增加了移植腎一年的存活率,然而移植腎的半壽期并未明顯提高,慢性移植腎病受到越來越多的關(guān)注。 移植腎冷缺血所造成的冷缺血再灌注損傷是臨床器官移植不可避免的病理生理過程,是慢性移植腎病的危險(xiǎn)因素之一。供腎的冷缺血時(shí)間(coldischemia time CIT)是造成腎移植患者術(shù)后發(fā)生移植腎功能延遲恢復(fù)(delayed graft function DGF)的主要原因,而DGF和急性排斥反應(yīng)(acute rejection episodes ARE)的發(fā)生是影響腎臟存活時(shí)間的重要因素 近年來的研究發(fā)現(xiàn),炎癥、免疫反應(yīng)參與了缺血再灌注損傷。缺血再灌注過程中炎癥細(xì)胞聚集增加、細(xì)胞因子表達(dá)上調(diào)及T細(xì)胞介導(dǎo)的免疫反應(yīng)等是造成腎組織損傷的重要因素。 免疫系統(tǒng)是機(jī)體在長期進(jìn)化中逐步形成的一套機(jī)制復(fù)雜的防御系統(tǒng),包括天然免疫和獲得性免疫�，F(xiàn)已廣泛認(rèn)為,獲得性免疫的激活需要先天性免疫系統(tǒng)的參與,尤其是先天性免疫系統(tǒng)中的TLRs家族,它們是先天性免疫的信號(hào)發(fā)動(dòng)受體,TLRs除了識(shí)別病原相關(guān)的分子模式(PAMP),如細(xì)菌、病毒、真菌和原蟲外,同樣能識(shí)別多種因素引起損傷時(shí)受損細(xì)胞或壞死細(xì)胞釋放的內(nèi)源性配體,如高遷移率族蛋白B1(high mobility group box 1,HMGB1)等,進(jìn)而引發(fā)一系列的炎癥反應(yīng). HMGB1是一類早在30多年前就發(fā)現(xiàn)的非組蛋白(nonhistone chromatin protein,NHCP),屬于高遷移率族蛋白(high mobility group protein,HMG)家族,早期的研究認(rèn)為HMGB1是一種核內(nèi)蛋白,通過與DNA的相互作用參與核內(nèi)諸如轉(zhuǎn)錄、復(fù)制、重組等復(fù)雜有序的功能過程。近年來的研究發(fā)現(xiàn),核外HMGB1可能具有“早期”和“晚期”炎癥介質(zhì)的作用,在關(guān)節(jié)炎、膿毒血癥、創(chuàng)傷、急性肺損傷、缺血再灌注損傷等各類急慢性炎疾病的中,HMGB1被證實(shí)扮演了重要的角色。 在目前國內(nèi)及國外的研究中,針對(duì)HMGB1的研究集中在以大鼠熱缺血再灌注為模型的動(dòng)物實(shí)驗(yàn)。研究提示內(nèi)源性配體(HMGB1)與TLRs結(jié)合能誘導(dǎo)樹突狀細(xì)胞(DC)的成熟,除了產(chǎn)生細(xì)胞因子和化學(xué)因子,成熟的DC表面共同刺激分子能提供“第二信號(hào)”給T淋巴細(xì)胞。TLRs與配體結(jié)合后在DC中通過T輔助細(xì)胞(TH細(xì)胞)激活來引發(fā)效應(yīng)。反之,若缺乏TLRs的外源性和內(nèi)源性配體,那么TLRs無法激活,則DC成熟障礙,而未成熟的DC不能啟動(dòng)T淋巴細(xì)胞反應(yīng)。腎臟冷缺血再灌注損傷機(jī)制、損傷特點(diǎn)尚不明確。 實(shí)驗(yàn)研究中,阻斷胞外HMGB1的活性,已成為干預(yù)相關(guān)疾病過程的重要策略。丙酮酸乙酯(Ethyl pyruvate,EP)是美國食品和藥品管理局劃分為無毒性物質(zhì)的一種食品添加劑,有顯著的抑制HMGB1的合成與釋放作用,對(duì)器官缺血再灌注損傷有保護(hù)作用,對(duì)其進(jìn)行進(jìn)一步研究具有重大的臨床價(jià)值。 本課題通過研究HMGB1在不同大鼠腎臟缺血再灌注模型中的表達(dá),以及應(yīng)用EP進(jìn)行干預(yù)的結(jié)果,旨在討論如下問題：1、構(gòu)建大鼠腎臟熱缺血再灌注損傷及冷缺血再灌注損傷,觀察缺血后不同時(shí)間段HMGB1,炎癥因子NF-κB、TNF-α的表達(dá),以及腎臟損傷程度；2、探討HMGB1啟動(dòng)腎臟熱、冷血再灌注損傷后獲得性免疫反應(yīng)的機(jī)制；3、對(duì)于大鼠熱缺血再灌注損傷進(jìn)行EP干預(yù)性治療,并觀察療效,并據(jù)此進(jìn)行大鼠冷缺血再灌注損傷治療,以提供防治腎臟冷缺血再灌注損傷的免疫學(xué)治療方案。在目前器官供體緊缺情況下,如何維持器官冷缺血時(shí)間更長的保存期,以拓寬供體的使用范圍,減少因供體冷缺血時(shí)間過長而導(dǎo)致移植后的移植物功能延遲恢復(fù)及移植器官病的發(fā)生率,延長移植腎半衰期,有重要的研究意義。 第一章HMGB1在熱缺血再灌注損傷中腎臟表達(dá)和干預(yù)研究 目的：探討HMGB1引發(fā)腎臟熱缺血再灌注損傷的途徑,明確HMGB1在熱缺血再灌注損傷中腎臟表達(dá),應(yīng)用EP進(jìn)行干預(yù)性治療,明確EP進(jìn)行治療的效果。方法：60只健康清潔級(jí)Sprague-Dawley (SD)雄性大鼠被隨機(jī)分為假手術(shù)組(n=20)、熱缺血再灌注組(n=20)、丙酮酸乙酯(EP)治療組(n=20)。采用夾閉左腎蒂使左側(cè)腎臟缺血45 min再恢復(fù)血流并切除右側(cè)腎臟制模。EP治療組缺血前20min及再灌注前分別經(jīng)陰莖背靜脈注射EP 3.26 g/L(溶于林格液1 ml中),假手術(shù)組和熱缺血再灌注組均經(jīng)陰莖背靜脈分別注射林格液1 ml,于術(shù)后6h、1d、3d、5d取下腔靜脈血檢測血肌酐、尿素氮水平,處死動(dòng)物后取腎臟組織標(biāo)本,應(yīng)用RT-QPCR方法檢測NF-κB、腫瘤壞死因子α(TNF-α),應(yīng)用western blot方法檢測HMGB1表達(dá)及免疫組化方法檢測腎臟損傷程度。 結(jié)果：熱缺血再灌注組及EP治療組HGMB1水平均高于正常對(duì)照組,其中熱缺血再灌注組高于EP治療組；熱缺血再灌注組和EP治療組血清CRE、BUN水平均顯著高于正常對(duì)照組,其中熱缺血再灌注組高于EP治療組；熱缺血再灌注組和EP治療組NF-κB、TNF-α水平均顯著高于正常對(duì)照組,其中熱缺血再灌注組高于EP治療組；熱缺血再灌注組及EP治療組腎臟損傷程度。 結(jié)論：各組腎臟標(biāo)本中均檢測到HMGB1的表達(dá),腎臟熱缺血再灌注損傷后HMGB1表達(dá)升高,導(dǎo)致CRE、BUN、TNF-α、NF-κB表達(dá)增高,應(yīng)用EP可減少HMGB1表達(dá),CRE、BUN、TNF-α、NF-κB升高程度減低,有助于減輕熱缺血再灌注所致腎損傷。 第二章HMGB1在冷缺血再灌注損傷中腎臟表達(dá)和干預(yù)治療 目的：探討HMGB1引發(fā)腎臟冷缺血再灌注損傷的機(jī)制,明確HMGB1在腎臟冷缺血再灌注損傷中的表達(dá)。根據(jù)熱缺血再灌注損傷試驗(yàn)結(jié)果,應(yīng)用EP進(jìn)行干預(yù)性治療,明確EP進(jìn)行治療的效果。 方法：60只健康清潔級(jí)Sprague-Dawley(SD)雄性大鼠被隨機(jī)分為假手術(shù)組、冷缺血再灌注組、丙酮酸乙酯(EP)治療組。構(gòu)建右腎冷缺血再灌注損傷模型。EP治療組缺血前20min及再灌注前分別經(jīng)陰莖背靜脈注射EP 3.26 g/L(溶于林格液1 ml中),假手術(shù)組和冷缺血再灌注組均經(jīng)陰莖背靜脈分別注射林格液1 ml,于術(shù)后6h、1d、3d、5d取下腔靜脈血檢測血肌酐、尿素氮水平,應(yīng)用RT-QPCR方法檢測NF-κB、腫瘤壞死因子α(TNF-α),處死動(dòng)物后取腎臟組織標(biāo)本,應(yīng)用western blot及免疫組化方法檢測腎組織HMGB1表達(dá)情況及腎臟損傷程度。 結(jié)果：冷缺血再灌注組及EP治療組HGMB1水平均高于正常對(duì)照組,其中冷缺血再灌注組高于EP治療組；冷缺血再灌注組和EP治療組血CRE、BUN水平均顯著高于正常對(duì)照組,其中冷缺血再灌注組高于EP治療組；冷缺血再灌注組和EP治療組NF-κB、TNFα水平均顯著高于正常對(duì)照組,其中冷缺血再灌注組高于EP治療組。 結(jié)論：各組腎臟標(biāo)本中均檢測到HMGB1的表達(dá),腎臟冷缺血再灌注損傷HMGB1、CRE、BUN、TNF-α、NF-κB變化趨勢與熱缺血再灌注損傷相同,但升高程度較低�？紤]損傷機(jī)制與熱缺血再灌注損傷相同,應(yīng)用EP阻斷HMGB1有助于減輕冷缺血再灌注所致腎損傷。
[Abstract]:Main text: Uremia is the end stage of chronic renal insufficiency, the new incidence rate is 0.01% every year in China, most of which are young adults, seriously affecting people's health and life safety. Kidney transplantation is the best treatment for end-stage renal disease, can significantly improve the quality of life of patients with end-stage renal disease, reduce complications. Although the incidence of perioperative complications and early acute rejection was significantly reduced with the improvement of transplantation techniques and the use of new immunosuppressive drugs, the one-year survival rate of transplanted kidneys was greatly increased. However, the half-life of transplanted kidneys was not significantly improved and chronic transplanted kidney disease was suffered. More and more attention.
Cold ischemia-reperfusion injury caused by cold ischemia is an inevitable pathophysiological process in clinical organ transplantation, and is one of the risk factors of chronic kidney transplantation. DGF and acute rejection episodes ARE are important factors affecting renal survival
In recent years, it has been found that inflammation and immune response are involved in ischemia-reperfusion injury. Increased aggregation of inflammatory cells, up-regulation of cytokine expression and T cell mediated immune response are important factors causing renal tissue injury during ischemia-reperfusion.
The immune system is a complex set of defense systems, including innate immunity and acquired immunity. It is widely believed that the activation of acquired immunity requires the involvement of innate immune system, especially the TLRs family in the innate immune system, which are signal-triggering receptors of innate immunity. In addition to recognizing pathogen-related molecular patterns (PAMPs), such as bacteria, viruses, fungi and protozoa, LRs can also identify endogenous ligands released by damaged or necrotic cells caused by various factors, such as high mobility group box 1 (HMGB1), which triggers a series of inflammatory reactions.
HMGB1 is a kind of non-histone chromatin protein (NHCP) discovered more than 30 years ago. It belongs to the high mobility group protein (HMG) family. Early studies suggested that HMGB1 is a kind of intranuclear protein, which participates in complex and orderly functions such as transcription, replication and recombination through the interaction with DNA. Recent studies have found that extranuclear HMGB1 may play an "early" and "late" role in inflammatory mediators. HMGB1 has been proved to play an important role in various acute and chronic inflammatory diseases such as arthritis, sepsis, trauma, acute lung injury, ischemia-reperfusion injury.
At present, studies on HMGB1 have focused on animal models of warm ischemia-reperfusion injury in rats. It is suggested that the binding of endogenous ligand (HMGB1) with TLRs can induce the maturation of dendritic cells (DC). In addition to the production of cytokines and chemical factors, the co-stimulatory molecules on the surface of mature DC can provide a "second message". TLRs bind to ligands and activate T helper cells (TH cells) in DCs to trigger the effect. Conversely, if TLRs are absent from the endogenous and exogenous ligands, then TLRs can not activate, then DC maturation is impaired, while immature DCs can not initiate T lymphocyte response. Vague.
Ethyl pyruvate (EP) is a kind of food additive classified as non-toxic substance by the Food and Drug Administration of the United States, which can significantly inhibit the synthesis and release of HMGB1 and protect organs from ischemia-reperfusion injury. It is of great clinical value to further study it.
The purpose of this study was to investigate the expression of HMGB1 in different rat models of renal ischemia-reperfusion and the results of EP intervention. The following questions were discussed: 1. To construct rat kidneys with warm ischemia-reperfusion injury and cold ischemia-reperfusion injury, to observe the expression of HMGB1, inflammatory factors NF-kappa B, TNF-alpha at different time intervals after ischemia, and to observe the expression of HMGB1, NF-kappa Secondly, to explore the mechanism of acquired immune response after cold blood reperfusion injury; thirdly, to observe the therapeutic effect of EP intervention on warm ischemia reperfusion injury in rats, and to treat cold ischemia reperfusion injury in rats, so as to provide immunological therapy for preventing and treating cold ischemia reperfusion injury in kidney. In the current situation of organ donor shortage, it is of great significance to study how to maintain a longer shelf life of cold ischemia in order to broaden the scope of use of donors, reduce the incidence of delayed graft function recovery and organ disease after transplantation due to long cold ischemia of donors, and prolong the half-life of transplanted kidneys.
Chapter 1 HMGB1 expression and intervention in renal ischemia / reperfusion injury
Objective: To explore the pathway of renal warm ischemia-reperfusion injury induced by HMGB1, to clarify the expression of HMGB1 in the kidney during warm ischemia-reperfusion injury, to apply EP intervention therapy, and to clarify the effect of EP treatment. Methods: 60 healthy clean Sprague-Dawley (SD) male rats were randomly divided into sham operation group (n=20), warm ischemia-reperfusion group (n=2). Ethyl pyruvate (EP) treatment group (n=20). The left kidney ischemia was restored for 45 minutes by clipping the left kidney pedicle and the right kidney was resected. EP 3.26 g/L (dissolved in Ringer's solution 1 ml) was injected into the dorsal penile vein 20 minutes before ischemia and before reperfusion in the EP treatment group, and EP 3.26 g/L (dissolved in Ringer's solution 1 ml) was injected through the dorsal penile vein in in the sham operation group and the warm ischemi Inferior vena cava blood was taken at 6 hours, 1 day, 3 days and 5 days after operation to detect serum creatinine and urea nitrogen levels. Kidney tissue samples were taken after death. NF-kappa B and tumor necrosis factor-alpha (TNF-alpha) were detected by RT-QPCR. The expression of HMGB1 was detected by Western blot and the degree of renal injury was detected by immunohistochemistry.
Results: The levels of HGMB1 in warm ischemia-reperfusion group and EP group were higher than those in normal control group, and the levels of CRE and BUN in warm ischemia-reperfusion group and EP group were higher than those in EP group. The levels of B and TNF-alpha were significantly higher in warm ischemia-reperfusion group than in EP group, and the degree of renal injury in warm ischemia-reperfusion group and EP group.
CONCLUSION: The expression of HMGB1 was detected in all renal specimens. The expression of HMGB1 increased after warm ischemia-reperfusion injury, which resulted in the increase of CRE, BUN, TNF-a and NF-kappa B. EP could decrease the expression of HMGB1, CRE, BUN, TNF-a and NF-kappa B, and help to reduce the renal injury induced by warm ischemia-reperfusion.
The second chapter is about the expression and intervention of HMGB1 in cold ischemia reperfusion injury.
Objective: To explore the mechanism of cold ischemia-reperfusion injury induced by HMGB1 and to clarify the expression of HMGB1 in cold ischemia-reperfusion injury of kidney.
METHODS: Sixty healthy clean Sprague-Dawley (SD) male rats were randomly divided into sham-operation group, cold ischemia-reperfusion group and ethyl pyruvate (EP) treatment group. The right kidney cold ischemia-reperfusion injury model was established. After 6 hours, 1 day, 3 days and 5 days, the serum creatinine, urea nitrogen, NF-kappa B, tumor necrosis factor-alpha (TNF-alpha) and HMGB1 in renal tissue were detected by RT-QPCR and immunohistochemistry. Expression and severity of kidney injury.
Results: The levels of HGMB1 in cold ischemia-reperfusion group and EP group were higher than those in normal control group, and the levels of CRE and BUN in cold ischemia-reperfusion group and EP group were higher than those in EP group. The level of NF alpha was significantly higher than that of the normal control group, and the cold ischemia reperfusion group was higher than that of the EP treatment group.
CONCLUSION: The expression of HMGB1 was detected in all renal specimens. The changes of HMGB1, CRE, BUN, TNF-a and NF-kappa B in cold ischemia-reperfusion injury of kidney were the same as those in warm ischemia-reperfusion injury, but the increase degree was lower. Injury.
【學(xué)位授予單位】：中國人民解放軍軍醫(yī)進(jìn)修學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2011
【分類號(hào)】：R363
本文編號(hào)：2221577
[Abstract]:Main text: Uremia is the end stage of chronic renal insufficiency, the new incidence rate is 0.01% every year in China, most of which are young adults, seriously affecting people's health and life safety. Kidney transplantation is the best treatment for end-stage renal disease, can significantly improve the quality of life of patients with end-stage renal disease, reduce complications. Although the incidence of perioperative complications and early acute rejection was significantly reduced with the improvement of transplantation techniques and the use of new immunosuppressive drugs, the one-year survival rate of transplanted kidneys was greatly increased. However, the half-life of transplanted kidneys was not significantly improved and chronic transplanted kidney disease was suffered. More and more attention.
Cold ischemia-reperfusion injury caused by cold ischemia is an inevitable pathophysiological process in clinical organ transplantation, and is one of the risk factors of chronic kidney transplantation. DGF and acute rejection episodes ARE are important factors affecting renal survival
In recent years, it has been found that inflammation and immune response are involved in ischemia-reperfusion injury. Increased aggregation of inflammatory cells, up-regulation of cytokine expression and T cell mediated immune response are important factors causing renal tissue injury during ischemia-reperfusion.
The immune system is a complex set of defense systems, including innate immunity and acquired immunity. It is widely believed that the activation of acquired immunity requires the involvement of innate immune system, especially the TLRs family in the innate immune system, which are signal-triggering receptors of innate immunity. In addition to recognizing pathogen-related molecular patterns (PAMPs), such as bacteria, viruses, fungi and protozoa, LRs can also identify endogenous ligands released by damaged or necrotic cells caused by various factors, such as high mobility group box 1 (HMGB1), which triggers a series of inflammatory reactions.
HMGB1 is a kind of non-histone chromatin protein (NHCP) discovered more than 30 years ago. It belongs to the high mobility group protein (HMG) family. Early studies suggested that HMGB1 is a kind of intranuclear protein, which participates in complex and orderly functions such as transcription, replication and recombination through the interaction with DNA. Recent studies have found that extranuclear HMGB1 may play an "early" and "late" role in inflammatory mediators. HMGB1 has been proved to play an important role in various acute and chronic inflammatory diseases such as arthritis, sepsis, trauma, acute lung injury, ischemia-reperfusion injury.
At present, studies on HMGB1 have focused on animal models of warm ischemia-reperfusion injury in rats. It is suggested that the binding of endogenous ligand (HMGB1) with TLRs can induce the maturation of dendritic cells (DC). In addition to the production of cytokines and chemical factors, the co-stimulatory molecules on the surface of mature DC can provide a "second message". TLRs bind to ligands and activate T helper cells (TH cells) in DCs to trigger the effect. Conversely, if TLRs are absent from the endogenous and exogenous ligands, then TLRs can not activate, then DC maturation is impaired, while immature DCs can not initiate T lymphocyte response. Vague.
Ethyl pyruvate (EP) is a kind of food additive classified as non-toxic substance by the Food and Drug Administration of the United States, which can significantly inhibit the synthesis and release of HMGB1 and protect organs from ischemia-reperfusion injury. It is of great clinical value to further study it.
The purpose of this study was to investigate the expression of HMGB1 in different rat models of renal ischemia-reperfusion and the results of EP intervention. The following questions were discussed: 1. To construct rat kidneys with warm ischemia-reperfusion injury and cold ischemia-reperfusion injury, to observe the expression of HMGB1, inflammatory factors NF-kappa B, TNF-alpha at different time intervals after ischemia, and to observe the expression of HMGB1, NF-kappa Secondly, to explore the mechanism of acquired immune response after cold blood reperfusion injury; thirdly, to observe the therapeutic effect of EP intervention on warm ischemia reperfusion injury in rats, and to treat cold ischemia reperfusion injury in rats, so as to provide immunological therapy for preventing and treating cold ischemia reperfusion injury in kidney. In the current situation of organ donor shortage, it is of great significance to study how to maintain a longer shelf life of cold ischemia in order to broaden the scope of use of donors, reduce the incidence of delayed graft function recovery and organ disease after transplantation due to long cold ischemia of donors, and prolong the half-life of transplanted kidneys.
Chapter 1 HMGB1 expression and intervention in renal ischemia / reperfusion injury
Objective: To explore the pathway of renal warm ischemia-reperfusion injury induced by HMGB1, to clarify the expression of HMGB1 in the kidney during warm ischemia-reperfusion injury, to apply EP intervention therapy, and to clarify the effect of EP treatment. Methods: 60 healthy clean Sprague-Dawley (SD) male rats were randomly divided into sham operation group (n=20), warm ischemia-reperfusion group (n=2). Ethyl pyruvate (EP) treatment group (n=20). The left kidney ischemia was restored for 45 minutes by clipping the left kidney pedicle and the right kidney was resected. EP 3.26 g/L (dissolved in Ringer's solution 1 ml) was injected into the dorsal penile vein 20 minutes before ischemia and before reperfusion in the EP treatment group, and EP 3.26 g/L (dissolved in Ringer's solution 1 ml) was injected through the dorsal penile vein in in the sham operation group and the warm ischemi Inferior vena cava blood was taken at 6 hours, 1 day, 3 days and 5 days after operation to detect serum creatinine and urea nitrogen levels. Kidney tissue samples were taken after death. NF-kappa B and tumor necrosis factor-alpha (TNF-alpha) were detected by RT-QPCR. The expression of HMGB1 was detected by Western blot and the degree of renal injury was detected by immunohistochemistry.
Results: The levels of HGMB1 in warm ischemia-reperfusion group and EP group were higher than those in normal control group, and the levels of CRE and BUN in warm ischemia-reperfusion group and EP group were higher than those in EP group. The levels of B and TNF-alpha were significantly higher in warm ischemia-reperfusion group than in EP group, and the degree of renal injury in warm ischemia-reperfusion group and EP group.
CONCLUSION: The expression of HMGB1 was detected in all renal specimens. The expression of HMGB1 increased after warm ischemia-reperfusion injury, which resulted in the increase of CRE, BUN, TNF-a and NF-kappa B. EP could decrease the expression of HMGB1, CRE, BUN, TNF-a and NF-kappa B, and help to reduce the renal injury induced by warm ischemia-reperfusion.
The second chapter is about the expression and intervention of HMGB1 in cold ischemia reperfusion injury.
Objective: To explore the mechanism of cold ischemia-reperfusion injury induced by HMGB1 and to clarify the expression of HMGB1 in cold ischemia-reperfusion injury of kidney.
METHODS: Sixty healthy clean Sprague-Dawley (SD) male rats were randomly divided into sham-operation group, cold ischemia-reperfusion group and ethyl pyruvate (EP) treatment group. The right kidney cold ischemia-reperfusion injury model was established. After 6 hours, 1 day, 3 days and 5 days, the serum creatinine, urea nitrogen, NF-kappa B, tumor necrosis factor-alpha (TNF-alpha) and HMGB1 in renal tissue were detected by RT-QPCR and immunohistochemistry. Expression and severity of kidney injury.
Results: The levels of HGMB1 in cold ischemia-reperfusion group and EP group were higher than those in normal control group, and the levels of CRE and BUN in cold ischemia-reperfusion group and EP group were higher than those in EP group. The level of NF alpha was significantly higher than that of the normal control group, and the cold ischemia reperfusion group was higher than that of the EP treatment group.
CONCLUSION: The expression of HMGB1 was detected in all renal specimens. The changes of HMGB1, CRE, BUN, TNF-a and NF-kappa B in cold ischemia-reperfusion injury of kidney were the same as those in warm ischemia-reperfusion injury, but the increase degree was lower. Injury.
【學(xué)位授予單位】：中國人民解放軍軍醫(yī)進(jìn)修學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2011
【分類號(hào)】：R363
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