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烏司他丁通過(guò)抑制高遷移率族蛋白B1信號(hào)轉(zhuǎn)導(dǎo)通路對(duì)大鼠早期放射性肺損傷的防治作用

發(fā)布時(shí)間:2018-06-06 18:04

  本文選題:烏司他丁 + 高遷移率族蛋白B; 參考:《中國(guó)臨床藥理學(xué)雜志》2017年22期


【摘要】:目的觀(guān)察烏司他丁對(duì)大鼠早期放射性肺損傷的防治作用及其機(jī)制。方法選取45只健康雌性SD大鼠,根據(jù)隨機(jī)數(shù)字表法將大鼠分為正常組、模型組和實(shí)驗(yàn)組,每組15只。正常組不做處理,其余2組均全胸接受6 MV-X射線(xiàn)單次照射20 Gy制作放射性肺損傷模型。實(shí)驗(yàn)組大鼠予照射后48 h起予以尾靜脈注射烏司他丁1×105U·kg-1qd,其余2組予以尾靜脈注射同等體積0.9%Na Cl溶液。2周后留取肺組織,蘇木精-伊紅(HE)染色觀(guān)察肺組織形態(tài),計(jì)數(shù)肺泡灌洗液白細(xì)胞和紅細(xì)胞數(shù),實(shí)時(shí)熒光定量聚合酶鏈?zhǔn)椒磻?yīng)(qRT-PCR)和免疫印跡法(Western blot)測(cè)定高遷移率族蛋白B1(HMGB1)、晚期糖基化終末產(chǎn)物受體(RAGE)、核轉(zhuǎn)錄因子kappa B(NF-κB)、腫瘤壞死因子α(TNF-α)、白細(xì)胞介素6(IL-6)和環(huán)氧合酶2(COX-2)的表達(dá)水平。結(jié)果 HE染色結(jié)果顯示,實(shí)驗(yàn)組大鼠肺泡炎癥程度較模型組顯著減輕,實(shí)驗(yàn)組肺泡灌洗液中白細(xì)胞和紅細(xì)胞數(shù)分別(3.42±1.53)×109/L,(3.95±1.24)×109/L,模型組為(7.04±2.18)×109/L,(7.12±1.35)×109/L,實(shí)驗(yàn)組均較模型組明顯減少(P0.05),但與正常組細(xì)胞數(shù)無(wú)明顯差異(P0.05)。正常組大鼠肺組織中HMGB1、RAGE、NF-ΚB、TNF-α、IL-6和COX-2 mRNA的表達(dá)分別為1.01±0.16,1.01±0.18,1.03±0.27,1.10±0.50,1.01±0.17和1.01±0.16;模型組中上述基因mRNA的表達(dá)分別為4.66±1.43,4.18±0.82,4.31±1.03,3.41±0.91,4.22±0.79和4.41±0.99;實(shí)驗(yàn)組中上述基因mRNA的表達(dá)分別為1.82±0.73,1.55±0.62,1.70±1.39,1.77±0.95,1.45±0.55和1.85±1.48。與模型組比較,實(shí)驗(yàn)組肺組織HMGB1信號(hào)通路表達(dá)水平均下降,差異均有統(tǒng)計(jì)學(xué)意義(均P0.05);實(shí)驗(yàn)組與正常組比較,各基因的表達(dá)水平差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。結(jié)論烏司他丁可通過(guò)干擾HMGB1信號(hào)通路的表達(dá)抑制胸部照射后大鼠肺組織炎性改變。
[Abstract]:Objective to observe the preventive and therapeutic effects of ulinastatin on early radiation induced lung injury in rats. Methods 45 healthy female SD rats were randomly divided into normal group, model group and experimental group with 15 rats in each group. No treatment was given in the normal group, and the other two groups received a single dose of 6 MV-X ray irradiation for 20 Gy to make the model of radiation induced lung injury. The rats in the experimental group were injected with ulinastatin 1 脳 105 U kg-1qdfrom 48 h after irradiation, and the other two groups were given the same volume of 0.9% NaCl solution for lung tissue extraction. The lung tissue was observed by hematoxylin-eosin (HEH) staining. Count the number of white blood cells and red blood cells in alveolar lavage fluid, The expression levels of high mobility group protein B1HMGB1, advanced glycosylation end product receptor ragger, nuclear transcription factor kappa Bnf NF- 魏 B, tumor necrosis factor 偽 -TNF- 偽, interleukin-6IL-6) and cyclooxygenase 2COX-2 were detected by real-time quantitative polymerase chain reaction (RT-PCR) and Western blottering (Western blot). The expression levels of B1-HMGB1, advanced glycation end product receptor (RAGEG), nuclear transcription factor (kappa), tumor necrosis factor- 偽 (TNF- 偽), interleukin-6 (IL-6) and cyclooxygenase 2COX-2) were determined. Results the results of HE staining showed that the degree of alveolar inflammation in the experimental group was significantly less than that in the model group. The number of leukocytes and erythrocytes in the alveolar lavage fluid of the experimental group was 3.42 鹵1.53 脳 10 9 / L, respectively, 3.95 鹵1.24 脳 10 9 / L, and that of the model group was 7.04 鹵2.18 脳 10 9 / L, 7.12 鹵1.35 脳 10 9 / L, respectively. Compared with the model group, the number of leukocytes and red blood cells in the experimental group was significantly lower than that in the model group, but there was no significant difference in cell number between the experimental group and the normal group. 姝e父緇勫ぇ榧犺偤緇勭粐涓璈MGB1,RAGE,NF-螝B,TNF-偽,IL-6鍜孋OX-2 mRNA鐨勮〃杈懼垎鍒負(fù)1.01鹵0.16,1.01鹵0.18,1.03鹵0.27,1.10鹵0.50,1.01鹵0.17鍜,

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