本文選題：他克莫司　切入點(diǎn)：缺血再灌注　出處：《天津醫(yī)科大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：目的:探討他克莫司預(yù)處理對大鼠肝臟缺血再灌注損傷的作用及其與肝臟缺血再灌注期HMGB1、HIF-1α和HO-1的關(guān)系。方法:將64只成熟SD大鼠隨機(jī)分為2大組,每組32只,分別應(yīng)用于建立大鼠肝臟熱IR模型和冷IR模型中。每種IR模型各分成4個(gè)小組,分別為假手術(shù)組、缺血再灌注組(對照組)、FK506低劑量處理組、FK506高劑量處理組。術(shù)后再灌注6h取材,比較各組大鼠血清轉(zhuǎn)氨酶水平;利用ELISA法檢測血清腫瘤壞死因子-α(tumor necrosis factor-α,TNF-α)、白細(xì)胞介素-6(interleukin-6,IL-6)、白細(xì)胞介素-1β(interleukin-1β,IL-1β)水平;采用HE染色觀察肝組織病理改變;通過實(shí)時(shí)熒光定量PCR(RT-q PCR)來觀察FK506預(yù)處理對HMGB1、血紅素加氧酶-1(heme oxygenase-1,HO-1)m RNA表達(dá)的影響;免疫組織化學(xué)法檢測HMGB1的分布變化;Western blot法檢測HMGB1、HIF-1α和HO-1蛋白表達(dá)情況。結(jié)果:經(jīng)FK506處理后的給藥組中,兩種IR模型大鼠轉(zhuǎn)氨酶ALT、AST,炎癥因子TNF-α、IL-6和IL-1β含量較未處理對照組均有不同程度降低。兩種IR模型中的對照組內(nèi)均觀察到肝血竇淤血、中性粒細(xì)胞浸潤和片狀壞死。相比之下,不同劑量的FK506處理組中病理學(xué)改變均明顯減輕。與假手術(shù)組相比,行IR的對照組中HMGB1的m RNA及蛋白表達(dá)顯著增加,但經(jīng)FK506預(yù)處理后表達(dá)明顯減少。在經(jīng)低劑量FK506預(yù)處理的大鼠中,熱IR模型和冷IR模型組的HIF-1α、HO-1表達(dá)均呈現(xiàn)明顯增加。結(jié)論:FK506預(yù)處理可以顯著減輕大鼠肝臟IR損傷,該作用可能是FK506通過降低HMGB1的表達(dá),抑制炎癥因子釋放及上調(diào)HIF-1α、HO-1表達(dá)發(fā)揮的。
[Abstract]:Objective: to investigate the effect of tacrolimus preconditioning on hepatic ischemia-reperfusion injury in rats and its relationship with HMGB1HIF-1 偽 and HO-1 during hepatic ischemia-reperfusion. Methods: 64 adult SD rats were randomly divided into two groups, 32 rats in each group. Each IR model was divided into four groups: sham-operated group and ischemia-reperfusion group (control group, FK506 low-dose treatment group, FK506 high-dose treatment group). The levels of serum aminotransferase (alt), tumor necrosis factor- 偽 (TNF- 偽), interleukin-6 (IL-6) and interleukin-1 尾 interleukin-1 尾 (IL-1 尾) were detected by ELISA assay, and the pathological changes of liver tissue were observed by HE staining. The effect of FK506 pretreatment on the expression of HMGB1, hemhemoxygenase-1 (HO-1) RNA was observed by real-time fluorescence quantitative PCR(RT-q. Immunohistochemical method was used to detect the distribution of HMGB1. The expression of HMGB1HIF-1 偽 and HO-1 protein was detected by Western blot. Results: in the group treated with FK506, the expression of HIF-1 偽 and HIF-1 偽 was detected by Western blot. The levels of alt, TNF- 偽, IL-6 and IL-1 尾 in the two IR models were significantly lower than those in the untreated control group. The hepatic sinusoidal congestion, neutrophil infiltration and flake necrosis were observed in the two IR models. Compared with sham-operated group, the expression of m RNA and protein of HMGB1 in the control group treated with IR was significantly increased. However, after pretreatment with FK506, the expression of HIF-1 偽 -tHO-1 was significantly increased in the rats pretreated with low-dose FK506. Conclusion the expression of HIF-1 偽 -HO-1 in the hot IR model group and the cold IR model group was significantly increased. Conclusion: FK506 pretreatment can significantly attenuate the hepatic IR injury in rats. This effect may be played by FK506 by reducing the expression of HMGB1, inhibiting the release of inflammatory factors and upregulating the expression of HIF-1 偽 -HO-1.
【學(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R657.3

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本文編號(hào)：1617501