CAJ | 학술논문

目的探讨重组人干扰素α1b(rhIFN-α1b)不同给药方式及剂量对呼吸道合胞病毒(RSV)感染小鼠的抗病毒作用及对酪氨酸蛋白激酶/信号传导与转录活化因子(JAK/STAT)信号通路的影响.方法将48只BALB/c小鼠按随机数字表法随机分为6组:阴性对照组,RSV感染模型组,rhIFN-α1b 12.5 μg、25.0μg、50.0 μ,g雾化吸入组和12.5μg/kg腹腔注射组.连续5d药物干预治疗,第6天无菌剖取小鼠左肺组织,HE染色观察各组小鼠肺组织病理学改变;免疫荧光染色观察STAT1和STAT2蛋白表达情况.结果RSV感染模型组肺组织炎性损伤明显,rhIFN-α1b治疗后炎性损伤均有不同程度恢复,其中rhIFN-α1b 50.0 μg雾化吸入组炎性损伤程度最轻,各组间比较差异均有统计学意义(P均＜0.05).RSV感染模型组STAT1和STAT2蛋白表达减弱,rhIFN-α1b治疗后不同程度提高受RSV抑制的STAT1、STAT2蛋白表达,rhIFN-Mb 50.0 μg雾化吸人组STAT1、STAT2蛋白表达增强最显著,各组间比较差异均有统计学意义(P均＜0.05).结论rhIFN-α1b对RSV有抗病毒作用,同时可提高受RSV感染小鼠抑制的JAK/STAT信号通路的活性,雾化吸入治疗效果优于腹腔注射,且在一定范围内雾化吸入的疗效与剂量呈正比.
목적 탐토중조인간우소α1b(rhIFN-α1b)불동급약방식급제량대호흡도합포병독(RSV)감염소서적항병독작용급대락안산단백격매/신호전도여전록활화인자(JAK/STAT)신호통로적영향.방법 장48지BALB/c소서안수궤수자표법수궤분위6조:음성대조조,RSV감염모형조,rhIFN-α1b 12.5 μg、25.0μg、50.0 μ,g무화흡입조화12.5μg/kg복강주사조.련속5d약물간예치료,제6천무균부취소서좌폐조직,HE염색관찰각조소서폐조직병이학개변;면역형광염색관찰STAT1화STAT2단백표체정황.결과RSV감염모형조폐조직염성손상명현,rhIFN-α1b치료후염성손상균유불동정도회복,기중rhIFN-α1b 50.0 μg무화흡입조염성손상정도최경,각조간비교차이균유통계학의의(P균＜0.05).RSV감염모형조STAT1화STAT2단백표체감약,rhIFN-α1b치료후불동정도제고수RSV억제적STAT1、STAT2단백표체,rhIFN-Mb 50.0 μg무화흡인조STAT1、STAT2단백표체증강최현저,각조간비교차이균유통계학의의(P균＜0.05).결론rhIFN-α1b대RSV유항병독작용,동시가제고수RSV감염소서억제적JAK/STAT신호통로적활성,무화흡입치료효과우우복강주사,차재일정범위내무화흡입적료효여제량정정비.
Obgective To investigate the impact of different ways and doses of recombinant human interferon o1b(rhIFN-α1b) on antiviral effect on respiratory syncytial virus(RSV)-effected mice and signal pathway of JAK/ STAT.Methods Forty-eight mice were divided randomly into 6 groups,negative control group,RSV-infection model group,12.5,25.0,50.0 μg rhIFN-α1 b atomization inhalation of intervention group,and 12.5 μg rhIFN-α 1 b injection of intervention group.After continuous drug therapy for 5 days,the left lung tissues of mice were aseptically dissected in the sixth day.Then it were observed lung tissue pathology changes by optical microscope,and expression of STAT1 and STAT2 protein with laser scanning confocal microscopy.Results It was observed that RSV-infection model mice's lungs had significant inflammatory injury under light microscope.After treatments of rhIFN-α 1b,it showed that the mice lung tissue had recovery of inflammation on different degrees.The group of inhaled rhIFN-o1b 50.0 μg was damaged on lightest degree.There were statistically significant differences between each group (all P ＜ 0.05).The expression of STAT1 and STAT2 protein in RSV-infection model mice's lungs decreased remarkably under fluorescene microscopy.Treatments of rhIFN-α 1b increased the expression of STAT1 and STAT2 inhibited by RSV-infection.The expression of STAT1 and STAT2 protein of the inhaled rhIFN-α1b 50.0 μg group increased significantly.The differences between groups were statistically significant(all P ＜ 0.05).Conclusions rhIFN-α 1 b played an important role in anti-RSV effects,simultaneously,it could improve the activity of JAK/STAT signal pathway inhibited by RSV-infection.The treatment effect of rhIFN-α 1b deliveried by atomization inhalation was better than that of intraperitoneal injection.And curative effect is proportional to the atomization inhalation dose within a certain range.