Page 62 - 202010

甲泼尼龙琥珀酸钠对自身免疫性肺气肿模型大鼠氧化应激和抗

内皮细胞抗体的影响 Δ

李佳艺 ，张 程 ，李本雪，张 野，张湘燕（贵州省人民医院呼吸与危重症医学科/国家卫生健康委员会肺脏免
#
＊
疫性疾病重点实验室，贵阳 550002）

中图分类号 R965 文献标志码 A 文章编号 1001-0408（2020）10-1208-05
DOI 10.6039/j.issn.1001-0408.2020.10.10

摘 要 目的：研究甲泼尼龙琥珀酸钠对自身免疫性肺气肿模型大鼠氧化应激和抗内皮细胞抗体（AECA）的影响。方法：将雄性
SD大鼠随机分为对照组、模型组和干预组，每组8只。除对照组大鼠腹腔注射等体积的完全弗氏佐剂外，模型组和干预组大鼠均
腹腔注射体外培养的人脐静脉内皮细胞+完全弗氏佐剂混合物以复制自身免疫性肺气肿模型；造模给药后第2天，干预组大鼠腹
腔注射甲泼尼龙琥珀酸钠10 mg/（kg·d），对照组和模型组大鼠均腹腔注射等体积的生理盐水，每日1次，连续21 d。末次给药后，
取各组大鼠右肺组织制作石蜡切片并行苏木精-伊红染色，观察肺组织病理变化，测量单位面积内的肺泡数（MAN）和内衬间隔
（MLI）；检测左肺肺泡灌洗液（BALF）中丙二醛（MDA）、还原型谷胱甘肽（GSH）含量和超氧化物歧化酶（SOD）、谷胱甘肽过氧化
物酶（GSH-Px）活性，以及 BALF 和血清中 AECA 含量。采用 Pearson 分析模型组大鼠 BALF 中 AECA 与 MDA、GSH、SOD、
GSH-Px的相关性。结果：与对照组比较，模型组大鼠肺组织可见明显的肺气肿病理变化，其MAN显著减少，MLI显著延长（P＜
0.01）；BALF 中 GSH 含量和 SOD、GSH-Px 活性均显著降低，BALF 中 MDA 含量以及 BALF、血清中 AECA 含量均显著升高（P＜
0.01）。与模型组比较，干预组大鼠肺组织的肺气肿病理变化明显改善，其MAN显著增加，MLI显著缩短（P＜0.01）；BALF中GSH
含量和 SOD、GSH-Px 活性均显著升高；BALF 中 MDA 含量以及 BALF、血清中 AECA 含量均显著降低（P＜0.01）。模型组大鼠
BALF 中的 AECA 与 MDA 呈正相关（r＝0.710，P＜0.05），与 GSH、SOD、GSH-Px 呈负相关（r＝－0.754、－0.781、－0.736，P＜
0.05）。结论：甲泼尼龙琥珀酸钠可能通过减轻氧化应激反应、抑制AECA的表达，从而达到预防自身免疫性肺气肿的目的。
关键词 自身免疫性肺气肿；氧化应激；抗内皮细胞抗体；甲泼尼龙琥珀酸钠；大鼠
Effects of Methylprednisolone Sodium Succinate on Oxidative Stress and AECA of Autoimmune
Emphysema Model Rats
LI Jiayi，ZHANG Cheng，LI Benxue，ZHANG Ye，ZHANG Xiangyan（Dept. of Respiratory and Critical
Medicine，Guizhou Provincial People’s Hospital/NHC Key Laboratory of Pulmonary Immunological Diseases，
Guiyang 550002，China）

ABSTRACT OBJECTIVE：To study the effects of methylprednisolone sodium succinate on oxidative stress and anti-endothelial
cell antibody （AECA） of autoimmune emphysema model rats. METHODS：Male SD rats were randomly divided into control
group，model group and intervention group，with 8 rats in each group. Except that control group was given same volume of
complete Freund’s adjuvant intraperitoneally，model group and intervention group were given the mixture of human umbilical vein
endothelial cells and complete Freund’s adjuvant intraperitoneally to establish the model of autoimmune emphysema. On 2nd day
after modeling，intervention group was intraperitoneally injected with 10 mg/（kg·d）methylprednisolone sodium succinate. Control
group and model group were intraperitoneally injected the same volume of normal saline，once a day，for consecutive 21 days.
After last medication，the right lung tissue of rats were taken for paraffin section and HE staining in each group，and the
pathological changes of lung tissue were observed. The mean alveolar number （MAN） and mean linear intercept （MLI） were
measured. The contents of MDA and GSH，the activities of SOD and glutathione peroxidase（GSH-Px）in bronchial alveolar lavage
fluid（BALF）of left lung were determined；the contents of AECA in BALF and serum were also determined. The correlation of
AECA with MDA，GSH，SOD and GSH-Px were determined in model group by Pearson analysis. RESULTS：Compared with
control group，the pathological changes of pulmonary emphysema were obvious in model group，MAN decreased significantly，and
MLI prolonged significantly （P＜0.01） ； GSH content，
Δ 基金项目：国家自然科学基金资助项目（No.81560012）；贵州省
GSH-Px and SOD activities in BALF were decreased
科技计划项目（No.黔科合〔2016〕支撑 2907，No.黔科合基础〔2017〕
significantly，the contents of AECA in BALF and serum were
1100，No.黔科合基础〔2019〕1195）
＊住院医师，硕士。研究方向：慢性阻塞性肺疾病的临床与基 increased significantly （P＜0.01）. Compared with model
础。E-mail：549120823@qq.com group，the pathological changes of pulmonary emphysema was
# 通信作者：主任医师，博士。研究方向：慢性阻塞性肺疾病的临 improved significantly in the intervention group， MAN
床与基础。E-mail：zhangcheng16@sina.com increased significantly，while MLI shortened significantly（P＜

·1208 · China Pharmacy 2020 Vol. 31 No. 10 中国药房 2020年第31卷第10期