摘要
目的探讨甲泼尼龙琥珀酸钠对自身免疫性肺气肿大鼠肺泡隔细胞凋亡的影响及作用机制,为研究慢性阻塞肺疾病(chronic obstructive pulmonary disease,COPD)发病机制及寻求新的治疗方法提供理论依据。方法 24只SD大鼠随机分为3组:佐剂对照组(n=8)、自身免疫性肺气胂模型组(简称模型组,n=8)及甲泼尼龙琥珀酸钠干预组(简称干预组,n=8)。将原代培养的人脐静脉内皮细胞及佐剂注入模型组大鼠腹腔内建立自身免疫性肺气肿模型,干预组同时腹腔内注入注射用甲泼尼龙琥珀酸钠10 mg/(kg·d)的剂量进行干预。佐剂对照组腹腔内只注射等量的佐剂。21 d后处死所有大鼠。每组均取肺组织切片进行苏木精-伊红(HE)染色观察病理形态学改变,并定量测定肺平均内衬间隔(mean linear intercept,MLI)、平均肺泡数(mean alveolar numbers,MAN),利用免疫组化法测定血管内皮生长因子(vascular endothelial growth factor,VEGF)、血管内皮细胞生长因子-2(vascular endothelial growth factor-recptor2,VEGFR-2)在肺内的表达;采用脱氧核糖核酸末端转移酶介导的dUTP缺口末端标记Terminal deoxynucleotidyl transferasemediated dUTP nick end labeling,TUNEL)技术检测肺泡隔细胞调亡。结果模型组MLI比佐剂对照组明显增高(P<0.05),但MAN比佐剂对照组明显降低(P<0.05);干预组MLI比模型组明显降低(P<0.05),但MAN比模型组明显增高(P<0.05)。模型组肺内VEGF、VEGFR-2的表达较佐剂对照组明显降低,干预组肺内VEGF、VEGFR-2的表达较模型组明显升高,差异均有统计学意义(P<0.05)。模型组肺泡间隔细胞凋亡指数(apoptosis index,AI)明显高于佐剂对照组;干预组AI低于模型组,但高于佐剂对照组,差异均有统计学意义(P<0.05)。结论肺组织内VEGF、VEGFR-2表达下降可能通过促进肺泡隔细胞凋亡,参与大鼠自身免疫性肺气肿的形成;甲泼尼龙琥珀酸钠可缓解自身免疫性肺气肿的形成,其机制可能与调控VEGF、VEGFR-2表达及抑制肺泡间隔细胞凋亡有关。
Objective To investigate the effects of methyprednislone on the expression of tumor alveolar septal cell apoptosis in autoimmune emphysema rats,in order to provide a theoretical basis for Chronic obstructive pulmonary disease(COPD)pathogenesis and it’s treatment.Methods 24 rats were randomly divided into three groups:normal control group (n=8 ),model group (n=8 )and intervention group (methylprednisolone sodium succinate,n=8).Intraperitoneal injection of primary cultured human umbilical vein endothelial cells were given to establish the autoimmune emphysema models,intervention group was injected with methylprednisolone at the meantime,and normal control group was received adjuvant only.Pathological changes were observed in lung tissues stained by hematoxylin eosin,mean liner intercept(MLI)and mean alveolar numbers(MAN)were measured.The localization of VEGF and VEGFR-2 in lung tissues were detected by immunohistochemical analysis.Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL)technique was carried out to detect the alveolar septal cells apoptosis. Results The MLI in model group was higher than that in normal control group,while MAN was lower(P<0.05 );MLI in intervention group was lower than that in model group,but the MAN was higher (P<0.05 ).The localization of VEGF and VEGFR-2 in lung tissues in model group were lower than that in normal control group,and those in intervention group were higher than that in model group,the difference were all statistically significant(P<0.05 ).AI of alveolar septal cell in model group was higher than that in normal control group,which in intervention group was higher than that in model group,the difference were all statistically significant(P<0.05).Conclusion The decreasing of VEGF and VEGFR-2 in lung tissues may cause alveolar septal cell apoptosis and contribute to the pathogenesis of autoimmune emphysema of rats.Methyprednislone can alleviate the form of autoimmune emphysema in rats,which may be ralated to the regulation of VEGF and VEGFR-2 expression and inhibition of alveolar septal cell apoptosis.
出处
《中国生化药物杂志》
CAS
北大核心
2014年第4期36-39,共4页
Chinese Journal of Biochemical Pharmaceutics
基金
贵州省科技厅和贵州省人民医院联合基金[SY(2010)3120]
国家自然基金资助项目(81060006)
"十二五"国家科技支撑计划课题(2013BAI09B09)
