Study On The Mechanism Of Endoplasmic Reticulum Stress Involved In Mesoporous And Nano Silica Particles Induced Apoptosis

Silica is a widely used material,its special nature in the biosensors,drug carriers,bioactive substances carrier and other biomedical areas has attracted a large number of researchers eyesights.Nano-silica is a typical lung poison,and its biosafety hinders its development in the biomedical field.Mesoporous silica is a new type of silica material developed in recent years.Compared with nano-silica,it has the characteristics of less toxic effect on the body,easy modification of the surface,and easy handling of the pores.The pore silica has attracted much attention in the field of bio-drug research.However,the results of the study on the toxicity of mesoporous silica are not in consistent.Therefore,the toxic effects of two kinds of materials on human alveolar epithelial cells(HPAEPIC)were induced by nano-silica and mesoporous silica.HPAEPIC apoptosis,activation of endoplasmic reticulum stress pathway and its molecular mechanism.The main experimental method:1.Mesoporous,nano-silica characterization The mesopores,nanosized silica morphology and particle size were measured by transmission electron microscopy.The particle size of nanometer and mesoporous silica particles in the cell culture medium was measured using a Malvern particle size analyzer Diameter and zeta potentials were used to analyze the specific surface area and pore size of nanomaterials using a fully automatic surface area and porosity analyzer.2.The effects of different concentrations of mesoporous and nano-silica on the activity of HPAEPIC were investigated by CCK-8.The morphological changes of cells were observed by inverted microscope.Flow cytometry was used to detect HPAEPIC The effect of mesoporous and nano-silica on the ultrastructure of HPAEPIC was observed by transmission electron microscopy.3.The effect of nano-silica on cell endoplasmic reticulum stress by RT-qPCR was measured by the endoplasmic reticulum stress-specific inhibitor 4-PBA before and after the nano-silica,mesoporous silica exposure HPAEPIC 24h The expression of BIP mRNA and CHOP mRNA was detected by Western Blot.The expression of BIP mRNA and CHOP mRNA was detected by Western blot.BIP mRNA and CHOP mRNA were expressed by BIP mRNA and CHOP mRNA.The level of decline,suggesting that the endoplasmic reticulum stress pathway involved in nano-silica,mesoporous silica induced HPAEPIC apoptosis.The results of our experiments:1.Nanometer and mesoporous silica.The morphology of nano-silica particles observed under TEM was irregular and spherical.The surface of the material was rough and the particle size distribution was concentrated at 16nm.The mesoporous silica was regular electron microscopy,Surrounded by the core of the shell structure of two parts,the shell structure of the distribution of the rules,the aperture of 3nm channels,uniform dispersion,no agglomeration phenomenon.The mesoporous silica had DMEM dispersed particle size of 854.3nm,the zeta potential For the-22.6mV,the two materials dispersed in the culture environment DMEM particle size and zeta potential results are almost the same.2.Nano,mesoporous silica on HPAEPIC cytotoxicity:nano-silica,mesoporous silica from cell viability changes.With the increase of the dose,the inhibitory effect of nano-silica and mesoporous silica on the cell was gradually enhanced,and the IC50 of the nano-silica HPAEPIC cells was 125.81μg/ml after 24h,and the mesoporous silica HPAEPIC cells were 5212.47μg/ml for 24 h,suggesting that HPAEPIC cells were more sensitive to the effect of nano-silica.Nano-silica,mesoporous silica-like cell morphological changes.Its specific performance:the number of cells decreased,cell morphology changes,cells become variable round shrinkage,increased vacuoles.Nano-silica,mesoporous dioxin-induced ultrastructural changes in HPAEPIC cells.Nano-silica and mesoporous silica can accumulate in the cell endoplasmic reticulum,nano-silica can cause cell microstructure such as mitochondria,endoplasmic reticulum damage,mesoporous silica on the role of micro-structure of cells is not as Nano-silica is serious.Nano-silica,mesoporous silica induced HPAEPIC cell apoptosis,endoplasmic reticulum stress pathway may be involved in nano-silica,mesoporous silica induced HPAEPIC apoptosis response.3.The expression of BIP and CHOP mRNA in HPAEPIC cells treated with nano-silica and mesoporous silica was detected by RT-qPCR.The expression of BIP and CHOP mRNA was detected by Western Blot before and after inclusion of endoplasmic reticulum stress-specific inhibitor 4-PBA BIP mRNA,CHOP mRNA expression,BIP mRNA,CHOP mRNA expression,BIP mRNA,CHOP mRNA expression level decreased,suggesting that endoplasmic reticulum stress pathway involved in nano-silica,Mesoporous silica-induced HPAEPIC cell apoptosis.Conclusions:In summary,mesoporous silica compared with nano-silica,the toxicity of human alveolar epithelial cells smaller,causing a lower degree of apoptosis,but also can be uptake by cells,leading to cell morphological changes,The mechanism of mesoporous silica-induced apoptosis of human alveolar epithelial cells may be related to the upregulation of BIP,CHOP gene and protein in endoplasmic reticulum stress pathway.This study provides a scientific basis for the full understanding and evaluation of the safety of mesoporous silica and its use in biomedical applications,and provides a scientific basis for the application of mesoporous silica in bio-drug loading...