Objective: To investigate the effect of isosorbide mononitrate (ISMN) targeted nanoparticles on inflammatory factors of sinusitis by establishing a rabbit model of rhinosinusitis. Methods: Thirty healthy rabbits, male and female, weighing 2.5-3.5 kg, were randomly divided into 6 groups with 5 rabbits in each group. Group A was the control group. The model of rabbit sinusitis was established in group B to F, and CT was used to confirm the model was successful. After placing tubes into the maxillary sinus in the group C to F, saline, 45 mg/ml ISMN, 45 mg/ml ISMN nanoparticles and 45 mg/ml ISMN targeted nanoparticles were used to wash the maxillary sinus, respectively. Blood samples were collected from the ear vein of rabbits on day 7, 14, 21, 28, 35 and 42 after modeling respectively. Changes in the expression levels of inflammatory factors in rabbits during the modeling process and after drug washing were detected by ELISA. After the drug intervention, the maxillary sinus mucosa was taken for real-time quantitative PCR to detect the changes in the mRNA level of inflammatory factors. SPSS 22.0 software was used to process the data. Results: Rabbit model of sinusitis was successfully established. ELISA showed that after the action of ISMN targeted nanoparticles of 1 week (42th day after modeling), the levels of (interleukin, IL) 4, IL-8, IL-17A and interferon γ (IFN-γ) in the blood were lower compared with that of 35th day after modeling, the difference was statistically significant (5.57±1.20 vs 19.73±0.68, 66.41±11.87 vs 154.68±13.13, 17.96±1.87 vs 28.23±0.80, 53.56±5.66 vs 111.93±7.29, all P<0.05). Compared with the ISMN nanoparticles and ISMN, the ISMN targeted nanoparticles reduced the levels of IL-4, IL-8, IL-17A and IFN-γ more obviously, the differences were statistically significant (13.26±1.43 vs 8.81±1.33 vs 7.14±2.16, 89.47±17.80 vs 41.07±7.77 vs 15.84±3.72, 10.28±2.07 vs 3.06±1.62 vs 1.82±0.90, 62.16±6.18 vs 35.12±4.62 vs 27.89±10.18, all P<0.05). Real-Time PCR showed that after the flushing of ISMN targeted nanoparticles, the levels of IL-4, IL-8, IL-17A and IFN-γ mRNA were lowest compared with that of the model group, ISMN nanoparticles and ISMN group. Conclusion: ISMN targeted nanoparticles can reduce the level of inflammatory factors in rabbit sinusitis model.
目的： 通过建立家兔鼻窦炎模型，研究单硝酸异山梨酯（isosorbide mononitrate，ISMN）靶向纳米颗粒对鼻窦炎炎性因子的作用。 方法： 健康家兔30只，雌雄不限，体重2.5~3.5 kg，以随机数字表法随机分为6组，每组5只。A组为空白对照组；B~F组建立家兔鼻窦炎模型，CT确认建模成功；C~F组对上颌窦进行置管后，分别用生理盐水、45 mg/ml的ISMN、45 mg/ml的ISMN纳米颗粒和45 mg/ml的ISMN靶向纳米颗粒进行冲洗。分别在造模的第7、14、21、28、35和42天对家兔耳缘静脉进行采血，通过酶联免疫吸附实验（ELISA）检测建模过程中及药物冲洗后家兔体内炎性因子表达水平的变化。药物干预结束后，取家兔上颌窦黏膜进行实时定量PCR，检测炎性因子mRNA水平的变化。采用SPSS 22.0软件对数据进行处理。 结果： 成功建立家兔鼻窦炎模型，ELISA结果显示ISMN靶向纳米颗粒冲洗1周后（即造模后第42天），家兔血液中白细胞介素（interleukin，IL）4、IL-8、IL-17A和γ干扰素（interferon γ，IFN-γ）的水平与造模后第35天相比均降低，差异有统计学意义（5.57±1.20比19.73±0.68，66.41±11.87比154.68±13.13，17.96±1.87比28.23±0.80，53.56±5.66比111.93±7.29，P值均<0.05）；ISMN靶向纳米颗粒使血液中IL-4、IL-8、IL-17A和IFN-γ水平的降低程度均优于ISMN纳米颗粒和ISMN，差异有统计学意义（13.26±1.43比8.81±1.33比7.14±2.16，89.47±17.80比41.07±7.77比15.84±3.72，10.28±2.07比3.06±1.62比1.82±0.90，62.16±6.18比35.12±4.62比27.89±10.18，P值均<0.05）。实时定量PCR结果显示，ISMN靶向纳米颗粒冲洗1周后，IL-4、IL-8、IL-17A和IFN-γ mRNA表达水平与模型组、ISMN纳米颗粒冲洗组和ISMN冲洗组相比水平均显著降低。 结论： ISMN靶向纳米颗粒可以降低家兔鼻窦炎模型体内的炎性因子水平。.
Keywords: Isosorbide mononitrate; Molecular targeted therapy; Rabbit; Sinusitis; Staphylococcus aureus.