title: [Effect of nano-TiO(2) intratracheal instillation on lipid metabolism of AopE gene-knockout mice].
abstract: OBJECTIVE
  To investigate the effect of nano-TiO(2) intratracheal instillation on the progression of dyslipidemia and atherosclerosis in apolipoprotein E-knockout mice.
  
  
  METHODS
  The nano-TiO(2) was ultrasound with phosphate-buffered saline solutions (PBS) into its suspension for exposure. A total of 46 specific pathogen free (SPF) level of 11-week-old male apolipoprotein E-knockout mice were randomly divided into groups by their body weights: non-treatment group (8 mice), PBS control group (9 mice), high dose group (1.0 mg/ml, 10 mice), medium dose group (0.5 mg/ml, 10 mice), and low dose group (0.1 mg/ml, 9 mice). Except the non-treatment group, mice from other groups were intratracheally instilled with 0.05 ml each time, twice a week. After exposure of 6 weeks, viscera index, blood TC, TG, HDL-C, LDL-C, and organic lipid ratio were assessed as biomarkers. Artery and aortic root issues were assessed by histopathology.
  
  
  RESULTS
  After 5 weeks exposure, mice body weights in high dose group ((29.7 ± 1.9) g) started to drop, compared to PBS control ((31.3 ± 1.9) g, t = -1.58, P < 0.05) and low dose group ((31.4 ± 1.4) g, t = -1.17, P < 0.05); after 6 weeks, high dose group ((28.8 ± 1.5) g) was lower than PBS control ((30.4 ± 1.9) g, t = -1.60, P < 0.05), non-treatment group ((30.2 ± 1.3) g, t = -1.43, P < 0.05) and low dose group ((30.6 ± 1.0) g, t = -1.83, P < 0.05). TC levels of non-treatment, PBS control, high dose group, medium dose group and low dose group were (2.92 ± 1.18), (3.12 ± 0.73), (4.19 ± 1.86), (3.46 ± 0.72) and (2.57 ± 0.64) mmol/L, respectively; TG levels were (0.39 ± 0.13), (0.39 ± 0.08), (0.60 ± 0.21), (0.55 ± 0.19) and (0.41 ± 0.11) mmol/L, respectively; HDL-C levels were (1.67 ± 0.45), (1.54 ± 0.67), (0.93 ± 0.50), (1.02 ± 0.48) and (1.31 ± 0.64) mmol/L; TG levels of high dose group were higher than that of non-treatment group (t = 1.27, P = 0.03) and low dose group (t = 1.62, P = 0.01); TG levels of medium dose group was higher than PBS control (t = 0.16, P = 0.04), and TC levels of high dose group were higher than PBS control (t = 0.22, P = 0.01), non-treatment group (t = 0.22, P = 0.04) and low dose group (t = 0.20, P = 0.03), and HDL-C levels of high dose group were lower than PBS control (t = -0.61, P = 0.04) and non-treatment group (t = -0.74, P = 0.04); organic lipid ratio of each group were (2.27 ± 0.51)%, (2.06 ± 0.53)%, (2.90 ± 0.50)%, (2.60 ± 0.23)%, (2.24 ± 0.45)%; high dose group were higher than PBS control (t = 0.85, P = 0.00), non-treatment group (t = 0.64, P = 0.03) and low dose group (t = 0.67, P = 0.01); medium dose group was higher than PBS control (t = 0.54, P = 0.02). The plaque lipid content and calcium content which showed the progression of atherosclerosis and plaque rupture were elevated in medium and high dose groups.
  
  
  CONCLUSIONS
  Intratracheal instillation of nano-TiO(2) can induce dyslipidemia and accelerate the development of atherosclerosis and plaque rupture in ApoE-/-mice.
authors.affiliation: Department of Occupational and Environmental Health, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Jie-qiong
authors.initials: JQ
authors.lastname: Hu
authors.forename: Chun-ying
authors.initials: CY
authors.lastname: Chen
authors.forename: Ru
authors.initials: R
authors.lastname: Bai
authors.forename: Sen
authors.initials: S
authors.lastname: Zhen
authors.forename: Xian-mei
authors.initials: XM
authors.lastname: DU
authors.forename: Jia-jie
authors.initials: JJ
authors.lastname: Zang
authors.forename: Jiu-cun
authors.initials: JC
authors.lastname: Li
authors.forename: Yi-qun
authors.initials: YQ
authors.lastname: Gu
authors.forename: Guang
authors.initials: G
authors.lastname: Jia
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000097:blood / Q000139:chemically induced*; D050171:Dyslipidemias / Q000097:blood / Q000139:chemically induced*; D007322:Instillation, Drug; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D053758:Nanoparticles; D013047:Specific Pathogen-Free Organisms; D014025:Titanium / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D001057:Apolipoproteins E; D008055:Lipids; C009495:titanium dioxide; D014025:Titanium