摘要
目的 利用载脂蛋白E（ApoE）基因敲除小鼠,观察气管滴注纳米二氧化钛（nano-TiO2）颗粒物对脂代谢、动脉粥样硬化症发展的影响及其机制.方法 nano-TiO2超声配成磷酸缓冲液（PBS）悬浮液用于染毒;46只无特定病原体（specific pathogen free,SPF）级11周龄的雄性AopE基因敲除小鼠,按体重应用随机数字表法分为非处理组（8只）、PBS溶剂对照组（9只）、高剂量组（1.0 mg/ml,10只）、中剂量组（0.5 mg/ml,10只）、低剂量组（0.1 mg/ml,9只）.除非处理组外,其余各组以每周2次,每次0.05 ml,分别进行无创气管滴注染毒6周,观察各组小鼠体重、血清总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、附睾周围脂肪体重比的变化,并进行主动脉动脉粥样病理观察.结果 染毒5周后,高剂量组小鼠体重[（29.7±1. 9）g]较PBS对照组[（31.3±1.9）g]和低剂量组[（31.4±1.4）g]下降,差异有统计学意义（t值分别为-1.58、-1.17,P值均〈0.05）;6周后,高剂量组[（28.8±1. 5）g]与PBS对照组[（30.4±1.9）g]、非处理组[（30.2±1.3）g]及低剂量组[（30.6±1.0）g]比较,体重下降,差异有统计学意义（t值分别为-1.60、-1.43、-1.83,P值均〈0.05）.6周后,非处理组、PBS对照组、高剂量组、中剂量组和低剂量组TC含量分别为（2.92±1. 18）、（3.12±0.73）、（4.19±1.86）、（3.46±0.72）、（2.57±0.64）mmol/L;TG为（0.39±0.13）、（0.39±0.08）、（0.60±0.21）、（0.55±0.19）、（0.41±0.11）mmol/L;HDL-C为（1.67±0.45）、（1.54±0.67）、（0.93±0.50）、（1.02±0.48）、（1.31±0.64）mmol/L,高剂量组TG高于非处理组（t=1.27,P=0.03）和低剂量组（t=1.62,P=0.01）,TC高于PBS组（t=0.22,P=0.01）、非处理组（t=0.22,P=0.04）和低剂量组（t=0.20,P=0.03）,HDL-C低于PBS对照组（t=-0.61,P=0.04）和非处理组（t=-0.74,P=0.04）;中剂量组TG高于PBS组（t=0.16,P=0.04）;脂肪体重比分别为（2.27±0.51）%、（2.06±0.53）%、（2.90±0.50）%、（2.60±0.23）%、（2.24±0.45）%,高剂量组高于PBS对照组（t=0.85,P=0.00）、非处理组（t=0.64,P=0.03）和低剂量组（t=0.67,P=0.01）,中剂量组高于PBS对照组（t=0.54,P=0.02）.病理观察提示高剂量组核心脂质占斑块面积大于其他各组;高、中剂量组包埋纤维帽数、钙化成分占斑块面积大于其他各组.结论 ApoE基因敲除小鼠气管滴注nano-TiO2后,能加重脂代谢紊乱,对动脉粥样硬化发展及诱导斑块破裂有一定影响.
Objective To investigate the effect of nano-TiO2 intratracheal instillation on the progression of dyslipidemia and atherosclerosis in apolipoprotein E-knockout mice. Methods The nano-TiO2 was ultrasouded 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 mediumd and high dose groups. Conclusion Intratracheal instillation of nano-TiO2 can induce dyslipidemia and accelerate the development of atherosclerosis and plaque rupture in ApoE -/-mice.
出处
《中华预防医学杂志》
CAS
CSCD
北大核心
2010年第9期780-784,共5页
Chinese Journal of Preventive Medicine
基金
国家自然科学基金（30771787）
人造纳米材料的生物安全性研究及解决方案探索（2006CB705600）
关键词
纳米结构
钛
小鼠
基因敲除
滴注
药物
血脂异常
Nanostructures
Titanium
Mice,knockout
Instillation,drug
Dyslipidemias
