药物载体用埃洛石纳米管的大鼠免疫安全性评价

Evaluation of halloysite nanotubes as drug carriers on immune safety in rats

[目的]探讨埃洛石纳米管(HNTs)引起大鼠的免疫调节机制及其免疫安全性评价。[方法]设空白对照组、HNTs仿口服组(低、中、高剂量)和仿吸入组(低、中、高剂量)。对健康大鼠连续摄入8周,1次/2 d,采集胸腺、脾组织和外周血血清样本,检测分析GSH、MDA、SOD、TNF-α、IFN-γ和IL-1等重要免疫指标,并采用HE染色法观察脾脏和胸腺的组织变化。[结果]与空白对照组相比:(1)GSH和TNF-α在两种摄入方式中的各剂量组间均无显著性差异;(2)MDA在仿吸入组的胸腺中、高剂量时含量显著性降低,脾脏高剂量组MDA显著性升高;(3)SOD在仿口服组的胸腺中的活力随剂量的增大而显著降低,在脾脏的高剂量组活力显著性降低,在仿吸入组的胸腺低、中剂量组活力显著性升高;(4)仿口服组的低、中剂量组IFN-γ含量显著性降低,而高剂量组则显著性升高,仿吸入组的低、中剂量组IFN-γ含量显著性降低;(5)IL-1在仿吸入服组的高剂量组含量显著性增高;(6)仿口服和仿吸入高剂量组大鼠脾脏和胸腺组织均未见明显异常。[结论]不同摄入途径、不同剂量的HNTs对免疫系统的影响方式和程度不一,氧化应激状态和细胞因子网络在整体调节中得到一定的平衡,其影响机制可能与HNTs对不同组织、器官的敏感程度和全身应激调节相关。

[Objective]To explore the immunomodulation mechanism and immune safety evaluation of halloysite nanotubes(HNTs)in rats.[Methods]There were the blank groups,oral groups(low,medium and high dose)and inhalation groups(low,medium and high dose).After the healthy rats were continuously infected with HNTs for 8 weeks(once every other day),the spleen,thymus and peripheral blood serum were collected for the detection of the important immune indicators:GSH、MDA、SOD、TNF-α、IFN-γand IL-1.HE staining was used to observe the changes of spleen and thymus.[Results]Compared with the blank group:(1)There was on significant difference between GSH and TNF-αin each dose group in the two intake modes.(2)MDA confent in the thgmus of the simulated inhalation group at high dose.(3)In oral group,the SOD of thymus decreased significantly with increasing dose,while the difference appeared only in high-dose group in the spleen.In inhalation group,the activity of low and middle dose groups was significantly increased in the thymus.(4)In oral group,the content of IFN-γin low and middle dose groups was significantly decreased,while that in high dose group was significantly increased.In inhalation group,the content of IFN-γin low and middle dose groups was significantly decreased.(5)In inhalation group,IL-1 in high dose group was significantly increased.(6)There were no obvious abnormalities in the spleen and thymus tissues of the high dose groups of oral and inhalation administration.[Conclusion]Different exposure routes and doses of HNTs have different effects on immune system.The oxidative stress state and cytokine network have a certain balance in the overall regulation,which may be related to the sensitivity of HNTs to different tissues and organs and the systemic stress regulation.