OBJECTIVE To investigate the effects of combined exposure of silica nanoparticles(SiNPs)and a high-fat diet(HFD)on aortic vascular fibrosis in rats and explore the underlying mecha-nisms.METHODS Transmission electron microscopy and a particle size analyzer were used to analyze the size and dispersion of SiNPs.Male Wistar rats were randomly divided into four groups:standard diet control group(STD-control),standard diet SiNPs group(STD+SiNPs),high-fat diet control group(HFD-control),and high-fat diet SiNPs group(HFD+SiNPs).The rats received intratracheal instillation of SiNPs(10 mg·kg-1)or saline combined with either an STD or HFD every four days for 90 days.Small animal ultrasound was used to evaluate vascular function and structure.Hematoxylin and eosin(HE)staining and Masson's staining were performed to analyze aortic pathology and fibrosis.Biochemical assays were conducted to measure superoxide dismutase(SOD)activity,malondialdehyde(MDA)contents,and the ratio of reduced gluta-thione/glutathione disulfide(GSH/GSSG).Immunohistochemistry and Western blotting were used to analyze the expression levels of mitophagy-related proteins phospha-tase and PTEN induced kinase 1(PINK1),E3 ubiquitinligase(Parkin),microtubule-associated protein 1 light chain 3B(LC3B),and P62,as well as vascular fibrosis marker proteins alpha-smooth muscle actin(α-SMA),typeⅠcollagen(Col-Ⅰ),and typeⅢcollagen(Col-Ⅲ).RESULTS Transmission electron micros-copy analysis showed that SiNPs had a uniform size(51.24±8.54)nm,regular morphology,and good dispersion.Compared with the STD-control group,the STD+SiNPs group exhibited a significant reduc-tion in the end-diastolic diameter of the left common carotid artery and aorta,along with a significant increase in intima-media thickness.Additionally,SOD activity decreased,MDA contents increased,and the GSH/GSSG ratio declined,indicating that SiNPs exposure induced oxidative damage and vascular dysfunction in the aorta.Pathological staining revealed that SiNPs caused inflammatory infiltration and vascular fibrosis in the aortic intima of rats.Notably,HFD exacerbated the vascular toxicity induced by SiNPs,suggesting a synergistic effect of their combined exposure.Mechanistically,immunohistochem-istry and Western blotting results showed that the combined exposure to SiNPs and HFD significantly upregulated the expressions of PINK1,Parkin,LC3BⅡ/Ⅰ,P62,α-SMA,Col-Ⅰ,and Col-Ⅲin the aorta.These findings suggested that SiNPs and HFD co-exposure might activate PINK1/Parkin-mediated mitophagy,contributing to the progression of aortic fibrosis.CONCLUSION Combined exposure to SiNPs and HFD might induce mitophagy through the PINK1/Parkin signaling pathway,leading to decreased vascular antioxidant capacity and fibrosis.These findings provided new evidence for the joint impact of SiNPs exposure and metabolic disorders on cardiovascular health.

OBJECTIVE To investigate the effects of combined exposure of silica nanoparticles(SiNPs)and a high-fat diet(HFD)on aortic vascular fibrosis in rats and explore the underlying mecha-nisms.METHODS Transmission electron microscopy and a particle size analyzer were used to analyze the size and dispersion of SiNPs.Male Wistar rats were randomly divided into four groups:standard diet control group(STD-control),standard diet SiNPs group(STD+SiNPs),high-fat diet control group(HFD-control),and high-fat diet SiNPs group(HFD+SiNPs).The rats received intratracheal instillation of SiNPs(10 mg·kg-1)or saline combined with either an STD or HFD every four days for 90 days.Small animal ultrasound was used to evaluate vascular function and structure.Hematoxylin and eosin(HE)staining and Masson's staining were performed to analyze aortic pathology and fibrosis.Biochemical assays were conducted to measure superoxide dismutase(SOD)activity,malondialdehyde(MDA)contents,and the ratio of reduced gluta-thione/glutathione disulfide(GSH/GSSG).Immunohistochemistry and Western blotting were used to analyze the expression levels of mitophagy-related proteins phospha-tase and PTEN induced kinase 1(PINK1),E3 ubiquitinligase(Parkin),microtubule-associated protein 1 light chain 3B(LC3B),and P62,as well as vascular fibrosis marker proteins alpha-smooth muscle actin(α-SMA),typeⅠcollagen(Col-Ⅰ),and typeⅢcollagen(Col-Ⅲ).RESULTS Transmission electron micros-copy analysis showed that SiNPs had a uniform size(51.24±8.54)nm,regular morphology,and good dispersion.Compared with the STD-control group,the STD+SiNPs group exhibited a significant reduc-tion in the end-diastolic diameter of the left common carotid artery and aorta,along with a significant increase in intima-media thickness.Additionally,SOD activity decreased,MDA contents increased,and the GSH/GSSG ratio declined,indicating that SiNPs exposure induced oxidative damage and vascular dysfunction in the aorta.Pathological staining revealed that SiNPs caused inflammatory infiltration and vascular fibrosis in the aortic intima of rats.Notably,HFD exacerbated the vascular toxicity induced by SiNPs,suggesting a synergistic effect of their combined exposure.Mechanistically,immunohistochem-istry and Western blotting results showed that the combined exposure to SiNPs and HFD significantly upregulated the expressions of PINK1,Parkin,LC3BⅡ/Ⅰ,P62,α-SMA,Col-Ⅰ,and Col-Ⅲin the aorta.These findings suggested that SiNPs and HFD co-exposure might activate PINK1/Parkin-mediated mitophagy,contributing to the progression of aortic fibrosis.CONCLUSION Combined exposure to SiNPs and HFD might induce mitophagy through the PINK1/Parkin signaling pathway,leading to decreased vascular antioxidant capacity and fibrosis.These findings provided new evidence for the joint impact of SiNPs exposure and metabolic disorders on cardiovascular health.