乌司他丁通过抑制高迁移率族蛋白B1信号转导通路对大鼠早期放射性肺损伤的防治作用
发布时间：2018-06-06 18:04
本文选题：乌司他丁 + 高迁移率族蛋白B ； 参考：《中国临床药理学杂志》2017年22期
【摘要】：目的观察乌司他丁对大鼠早期放射性肺损伤的防治作用及其机制。方法选取45只健康雌性SD大鼠,根据随机数字表法将大鼠分为正常组、模型组和实验组,每组15只。正常组不做处理,其余2组均全胸接受6 MV-X射线单次照射20 Gy制作放射性肺损伤模型。实验组大鼠予照射后48 h起予以尾静脉注射乌司他丁1×105U·kg-1qd,其余2组予以尾静脉注射同等体积0.9%Na Cl溶液。2周后留取肺组织,苏木精-伊红(HE)染色观察肺组织形态,计数肺泡灌洗液白细胞和红细胞数,实时荧光定量聚合酶链式反应(qRT-PCR)和免疫印迹法(Western blot)测定高迁移率族蛋白B1(HMGB1)、晚期糖基化终末产物受体(RAGE)、核转录因子kappa B(NF-κB)、肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)和环氧合酶2(COX-2)的表达水平。结果 HE染色结果显示,实验组大鼠肺泡炎症程度较模型组显著减轻,实验组肺泡灌洗液中白细胞和红细胞数分别(3.42±1.53)×109/L,(3.95±1.24)×109/L,模型组为(7.04±2.18)×109/L,(7.12±1.35)×109/L,实验组均较模型组明显减少(P0.05),但与正常组细胞数无明显差异(P0.05)。正常组大鼠肺组织中HMGB1、RAGE、NF-ΚB、TNF-α、IL-6和COX-2 mRNA的表达分别为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;模型组中上述基因mRNA的表达分别为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;实验组中上述基因mRNA的表达分别为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。与模型组比较,实验组肺组织HMGB1信号通路表达水平均下降,差异均有统计学意义(均P0.05);实验组与正常组比较,各基因的表达水平差异无统计学意义(P0.05)。结论乌司他丁可通过干扰HMGB1信号通路的表达抑制胸部照射后大鼠肺组织炎性改变。
[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 伪 -TNF- 伪, 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- 伪 (TNF- 伪), 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 卤1.53 脳 10 9 / L, respectively, 3.95 卤1.24 脳 10 9 / L, and that of the model group was 7.04 卤2.18 脳 10 9 / L, 7.12 卤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父缁勫ぇ榧犺偤缁勭粐涓璈MGB1,RAGE,NF-螝B,TNF-伪,IL-6鍜孋OX-2 mRNA鐨勮〃杈惧垎鍒负1.01卤0.16,1.01卤0.18,1.03卤0.27,1.10卤0.50,1.01卤0.17鍜，
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