依达拉奉对大鼠慢性阻塞性肺病干预作用的研究

发布时间：2018-05-30 09:50

本文选题：依达拉奉 + COPD　；参考：《南华大学》2014年硕士论文

【摘要】：目的：研究自由基清除剂依达拉奉对慢性阻塞性肺病（COPD）大鼠肺损伤的作用，并探讨其可能的作用机制，开拓依达拉奉对COPD的临床应用价值。方法：健康雄性SD大鼠60只随机分为6组，即空白对照组（空白组）、COPD模型组（COPD组）、N-乙酰半胱氨酸（NAC）阳性药物对照组（NAC组）、依达拉奉低剂量组（Eda1组）、依达拉奉中剂量组（Eda2组）和依达拉奉高剂量组（Eda3组）。COPD模型组：参照宋一平脂多糖（LPS）气管内滴入加被动吸烟法（LPS+熏烟）复制COPD大鼠模型；NAC组：运用同样的造模方法复制COPD大鼠模型，每次被动吸烟前予以NAC（20mg/kg）腹腔注射；依达拉奉低、中、高剂量组：造模方法同COPD模型组，每次熏烟前分别予以依达拉奉10mg/kg、20mg/kg、40mg/kg腹腔注射。空白对照组：不做熏烟处理，气管滴注及腹腔注射均予以生理盐水。造模4周后，测定大鼠肺功能，经微机处理计算出呼吸频率（f）、呼气阻力（RI）、动态肺顺应性（Cdyn）及吸气峰流速（PIF）。取血，检测各组大鼠血浆丙二醛（MDA）水平和超氧化物歧化酶（SOD）活力。取大鼠支气管肺泡灌洗液（BALF），进行白细胞计总数、白细胞分类计数，测定BALF上清液肿瘤坏死因子α（TNF-α）、白细胞介素8（IL-8）的水平。取右上肺做病理切片，HE染色，测量平均内衬间隔（MLI）和平均肺泡数（MAN），免疫组化方法检测各组大鼠肺组织中基质金属蛋白酶9（MMP-9）、基质金属蛋白酶12（MMP-12）、组织金属蛋白酶抑制因子（TIMP-1）的表达。结果：1. COPD组大鼠f、RI明显高于空白组，差异有统计学意义（p0.05），而Cdyn、PIF显著降低，与空白组有显著性差异（p0.05），NAC与中、高剂量的依达拉奉可以显著改善大鼠RI、Cdyn、PIF，差异有统计学意义（p0.05）。 2. COPD模型组大鼠血浆氧化产物MDA水平显著升高，与空白组相比，差异有统计学意义（p0.05）。NAC与各剂量的的依达拉奉均能降低大鼠血浆MDA水平，差异有统计学意义（p0.05）。 3. COPD组大鼠白细胞总数与中性粒细胞百分率明显增加，差异有统计学意义（p0.05）。NAC与中、高剂量的依达拉奉可以显著降低白细胞总数，差异有统计学意义（p0.05），中性粒细胞百分率可被NAC及高剂量的依达拉奉降低，差异有统计学意义（p0.05）。COPD组大鼠BALF中TNF-α水平显著升高，差异有统计学意义（p0.05），NAC与各剂量的依达拉奉均可降低大鼠BALF中TNF-α水平，差异有统计学意义（p0.05）。 4.COPD组大鼠肺组织呈现肺泡融合、肺泡腔扩张等明显肺气肿样病理改变，NAC组及Eda3组病理变化相对减轻。COPD组大鼠与空白组相比，平均内衬间隔（MLI）明显增加，平均肺泡数（MAN）显著减少，差异均有统计学意义（p0.05）。NAC与中、高剂量的依达拉奉可以减小MLI，增加MAN，差异有统计学意义（p0.05）。 5. COPD组大鼠支气管肺组织MMP-9、MMP-12及TIMP-1表达显著增加，MMP-9/TIMP-1和MMP-12/TIMP-1比值增大，，与空白组相比差异均有统计学意义（p0.05）。NAC及中、高剂量的依达拉奉可以抑制MMP-9、MMP-12和TIMP-1的表达，降低MMP-9/TIMP-1和MMP-12/TIMP-1比值，与COPD组相比，差异均具有统计学意义（p0.05）。结论：大鼠造模过程中同时给予药物干预可以延缓COPD的病理进程，NAC和中、高剂量的依达拉奉可通过抗氧化，抑制炎症细胞聚集，抑制炎症因子释放，降低蛋白酶的表达，平衡蛋白酶/抗蛋白酶系统而发挥一定的抗COPD作用。
[Abstract]:Objective : To study the effect of free radical scavenging agent Edara on lung injury in rats with chronic obstructive pulmonary disease ( COPD ) , and to explore its possible mechanism of action and to explore the clinical application value of Edara in COPD .

Methods : 60 healthy male SD rats were randomly divided into six groups : blank control group ( blank group ) , COPD model group ( COPD group ) , N - acetyl cysteine ( NAC ) positive drug control group ( NAC group ) , Eda1 group ( Eda1 group ) , Eda2 group ( Eda2 group ) and Eda3 group ( Eda3 group ) .
NAC group : Using the same molding method to replicate the model of COPD rats , NAC ( 20 mg / kg ) was injected intraperitoneally before each passive smoking ;
The levels of plasma malondialdehyde ( MDA ) and superoxide dismutase ( SOD ) in lung tissues of rats were measured by computer . The expression of matrix metalloproteinase 9 ( MMP - 9 ) , matrix metalloproteinase 12 ( MMP - 12 ) and tissue inhibitor of metalloproteinase - 1 ( TIMP - 1 ) in lung tissues of rats were measured .

Results : 1 . In COPD group , f and RI were significantly higher than those in the blank group ( p < 0.05 ) , but there was a significant difference between the two groups ( p < 0.05 ) .

2 . Compared with blank group , the level of MDA in plasma oxidation products of COPD model group was significantly higher than that in blank group ( p < 0.05 ) .

3 . The total number of white blood cells and neutrophil percentage increased significantly in COPD group ( p < 0.05 ) . The difference was statistically significant ( p < 0.05 ) . The level of TNF - 伪 in BALF of COPD group was significantly increased ( p < 0.05 ) . The level of TNF - 伪 in BALF of COPD group was significantly decreased ( p < 0.05 ) .

4 . Compared with the blank group , the mean liner spacing ( MLI ) was significantly increased and the mean alveolar number ( MAN ) was significantly decreased compared with the blank group ( p 0.05 ) .

5 . The expression of MMP - 9 , MMP - 12 and TIMP - 1 in broncho - lung tissues of COPD group was significantly increased , and the ratio of MMP - 9 / TIMP - 1 and MMP - 12 / TIMP - 1 increased significantly ( p < 0.05 ) .

Conclusion : At the same time , drug intervention can delay the pathological process of COPD , NAC and middle and high doses of Edara can exert a certain anti - COPD effect by resisting oxidation , inhibiting inflammation cell aggregation , inhibiting the release of inflammatory factors , reducing the expression of protease , balancing the protease / protease system .
【学位授予单位】：南华大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R965

【参考文献】