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.
目的 利用載脂蛋白E(ApoE)基因敲除小鼠,觀察氣管滴註納米二氧化鈦(nano-TiO2)顆粒物對脂代謝、動脈粥樣硬化癥髮展的影響及其機製.方法 nano-TiO2超聲配成燐痠緩遲液(PBS)懸浮液用于染毒;46隻無特定病原體(specific pathogen free,SPF)級11週齡的雄性AopE基因敲除小鼠,按體重應用隨機數字錶法分為非處理組(8隻)、PBS溶劑對照組(9隻)、高劑量組(1.0 mg/ml,10隻)、中劑量組(0.5 mg/ml,10隻)、低劑量組(0.1 mg/ml,9隻).除非處理組外,其餘各組以每週2次,每次0.05 ml,分彆進行無創氣管滴註染毒6週,觀察各組小鼠體重、血清總膽固醇(TC)、甘油三酯(TG)、高密度脂蛋白膽固醇(HDL-C)、低密度脂蛋白膽固醇(LDL-C)、附睪週圍脂肪體重比的變化,併進行主動脈動脈粥樣病理觀察.結果 染毒5週後,高劑量組小鼠體重[(29.7±1. 9)g]較PBS對照組[(31.3±1.9)g]和低劑量組[(31.4±1.4)g]下降,差異有統計學意義(t值分彆為-1.58、-1.17,P值均<0.05);6週後,高劑量組[(28.8±1. 5)g]與PBS對照組[(30.4±1.9)g]、非處理組[(30.2±1.3)g]及低劑量組[(30.6±1.0)g]比較,體重下降,差異有統計學意義(t值分彆為-1.60、-1.43、-1.83,P值均<0.05).6週後,非處理組、PBS對照組、高劑量組、中劑量組和低劑量組TC含量分彆為(2.92±1. 18)、(3.12±0.73)、(4.19±1.86)、(3.46±0.72)、(2.57±0.64)mmol/L;TG為(0.39±0.13)、(0.39±0.08)、(0.60±0.21)、(0.55±0.19)、(0.41±0.11)mmol/L;HDL-C為(1.67±0.45)、(1.54±0.67)、(0.93±0.50)、(1.02±0.48)、(1.31±0.64)mmol/L,高劑量組TG高于非處理組(t=1.27,P=0.03)和低劑量組(t=1.62,P=0.01),TC高于PBS組(t=0.22,P=0.01)、非處理組(t=0.22,P=0.04)和低劑量組(t=0.20,P=0.03),HDL-C低于PBS對照組(t=-0.61,P=0.04)和非處理組(t=-0.74,P=0.04);中劑量組TG高于PBS組(t=0.16,P=0.04);脂肪體重比分彆為(2.27±0.51)%、(2.06±0.53)%、(2.90±0.50)%、(2.60±0.23)%、(2.24±0.45)%,高劑量組高于PBS對照組(t=0.85,P=0.00)、非處理組(t=0.64,P=0.03)和低劑量組(t=0.67,P=0.01),中劑量組高于PBS對照組(t=0.54,P=0.02).病理觀察提示高劑量組覈心脂質佔斑塊麵積大于其他各組;高、中劑量組包埋纖維帽數、鈣化成分佔斑塊麵積大于其他各組.結論 ApoE基因敲除小鼠氣管滴註nano-TiO2後,能加重脂代謝紊亂,對動脈粥樣硬化髮展及誘導斑塊破裂有一定影響.
목적 이용재지단백E(ApoE)기인고제소서,관찰기관적주납미이양화태(nano-TiO2)과립물대지대사、동맥죽양경화증발전적영향급기궤제.방법 nano-TiO2초성배성린산완충액(PBS)현부액용우염독;46지무특정병원체(specific pathogen free,SPF)급11주령적웅성AopE기인고제소서,안체중응용수궤수자표법분위비처리조(8지)、PBS용제대조조(9지)、고제량조(1.0 mg/ml,10지)、중제량조(0.5 mg/ml,10지)、저제량조(0.1 mg/ml,9지).제비처리조외,기여각조이매주2차,매차0.05 ml,분별진행무창기관적주염독6주,관찰각조소서체중、혈청총담고순(TC)、감유삼지(TG)、고밀도지단백담고순(HDL-C)、저밀도지단백담고순(LDL-C)、부고주위지방체중비적변화,병진행주동맥동맥죽양병리관찰.결과 염독5주후,고제량조소서체중[(29.7±1. 9)g]교PBS대조조[(31.3±1.9)g]화저제량조[(31.4±1.4)g]하강,차이유통계학의의(t치분별위-1.58、-1.17,P치균<0.05);6주후,고제량조[(28.8±1. 5)g]여PBS대조조[(30.4±1.9)g]、비처리조[(30.2±1.3)g]급저제량조[(30.6±1.0)g]비교,체중하강,차이유통계학의의(t치분별위-1.60、-1.43、-1.83,P치균<0.05).6주후,비처리조、PBS대조조、고제량조、중제량조화저제량조TC함량분별위(2.92±1. 18)、(3.12±0.73)、(4.19±1.86)、(3.46±0.72)、(2.57±0.64)mmol/L;TG위(0.39±0.13)、(0.39±0.08)、(0.60±0.21)、(0.55±0.19)、(0.41±0.11)mmol/L;HDL-C위(1.67±0.45)、(1.54±0.67)、(0.93±0.50)、(1.02±0.48)、(1.31±0.64)mmol/L,고제량조TG고우비처리조(t=1.27,P=0.03)화저제량조(t=1.62,P=0.01),TC고우PBS조(t=0.22,P=0.01)、비처리조(t=0.22,P=0.04)화저제량조(t=0.20,P=0.03),HDL-C저우PBS대조조(t=-0.61,P=0.04)화비처리조(t=-0.74,P=0.04);중제량조TG고우PBS조(t=0.16,P=0.04);지방체중비분별위(2.27±0.51)%、(2.06±0.53)%、(2.90±0.50)%、(2.60±0.23)%、(2.24±0.45)%,고제량조고우PBS대조조(t=0.85,P=0.00)、비처리조(t=0.64,P=0.03)화저제량조(t=0.67,P=0.01),중제량조고우PBS대조조(t=0.54,P=0.02).병리관찰제시고제량조핵심지질점반괴면적대우기타각조;고、중제량조포매섬유모수、개화성분점반괴면적대우기타각조.결론 ApoE기인고제소서기관적주nano-TiO2후,능가중지대사문란,대동맥죽양경화발전급유도반괴파렬유일정영향.
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.
