临床心血管病杂志
臨床心血管病雜誌
림상심혈관병잡지
JOURNAL OF CLINICAL CARDIOLOGY
2009年
10期
788-792
,共5页
谢江娇%廖玉华%余娴%陈健%姚瑞%陈勇%廖孟阳%丁英俊%唐婷婷%程翔
謝江嬌%廖玉華%餘嫻%陳健%姚瑞%陳勇%廖孟暘%丁英俊%唐婷婷%程翔
사강교%료옥화%여한%진건%요서%진용%료맹양%정영준%당정정%정상
动脉粥样硬化%多聚ADP核糖合成酶%高同型半胱氨酸血症
動脈粥樣硬化%多聚ADP覈糖閤成酶%高同型半胱氨痠血癥
동맥죽양경화%다취ADP핵당합성매%고동형반광안산혈증
atherosclerosis%hyperhomocysteinemia%oxidative stress%Poly (ADP-ribose) polymerase inhibitor
目的:检测多聚ADP核糖合成酶[Poly (ADP-ribose) polymerase,PARP]抑制剂3-aminobenzamide (3-AB)是否能够降低由高同型半胱氨酸血症(Hyperhomocysteinemia, Hhcy)诱发ApoE-/-小鼠动脉粥样硬化的斑块面积.方法:健康6周龄雄性ApoE-/-小鼠随机分为普通饮食组(n=30)或高甲硫氨酸饮食组(n=30),每组再分别给予隔天腹腔注射10 mg/kg 3-AB(n=20)或0.9%氯化钠(n=20),持续12周.12周末,检测血脂及血浆同型半胱氨酸(homocysteine, Hcy)含量,分离心脏及主动脉,测量斑块面积,检测斑块局部NADPH氧化酶亚单位p47phox含量、PARP活性及表达.结果:高甲硫氨酸饮食诱导ApoE-/-小鼠产生Hhcy,促进氧化应激相关p47phox表达及PARP活化,显著增加斑块面积;PARP抑制剂3-AB虽然对普食组ApoE-/-小鼠抑制效果不明显,却能在不影响血浆Hcy和脂质含量的情况下,抑制Hhcy诱导的PARP活化,显著降低其粥样斑块面积达40%.结论:PARP抑制剂3-AB显著降低Hhcy诱导的ApoE-/-小鼠动脉粥样硬化斑块面积,可作为有效抑制粥样斑块进程的治疗方法之一.
目的:檢測多聚ADP覈糖閤成酶[Poly (ADP-ribose) polymerase,PARP]抑製劑3-aminobenzamide (3-AB)是否能夠降低由高同型半胱氨痠血癥(Hyperhomocysteinemia, Hhcy)誘髮ApoE-/-小鼠動脈粥樣硬化的斑塊麵積.方法:健康6週齡雄性ApoE-/-小鼠隨機分為普通飲食組(n=30)或高甲硫氨痠飲食組(n=30),每組再分彆給予隔天腹腔註射10 mg/kg 3-AB(n=20)或0.9%氯化鈉(n=20),持續12週.12週末,檢測血脂及血漿同型半胱氨痠(homocysteine, Hcy)含量,分離心髒及主動脈,測量斑塊麵積,檢測斑塊跼部NADPH氧化酶亞單位p47phox含量、PARP活性及錶達.結果:高甲硫氨痠飲食誘導ApoE-/-小鼠產生Hhcy,促進氧化應激相關p47phox錶達及PARP活化,顯著增加斑塊麵積;PARP抑製劑3-AB雖然對普食組ApoE-/-小鼠抑製效果不明顯,卻能在不影響血漿Hcy和脂質含量的情況下,抑製Hhcy誘導的PARP活化,顯著降低其粥樣斑塊麵積達40%.結論:PARP抑製劑3-AB顯著降低Hhcy誘導的ApoE-/-小鼠動脈粥樣硬化斑塊麵積,可作為有效抑製粥樣斑塊進程的治療方法之一.
목적:검측다취ADP핵당합성매[Poly (ADP-ribose) polymerase,PARP]억제제3-aminobenzamide (3-AB)시부능구강저유고동형반광안산혈증(Hyperhomocysteinemia, Hhcy)유발ApoE-/-소서동맥죽양경화적반괴면적.방법:건강6주령웅성ApoE-/-소서수궤분위보통음식조(n=30)혹고갑류안산음식조(n=30),매조재분별급여격천복강주사10 mg/kg 3-AB(n=20)혹0.9%록화납(n=20),지속12주.12주말,검측혈지급혈장동형반광안산(homocysteine, Hcy)함량,분리심장급주동맥,측량반괴면적,검측반괴국부NADPH양화매아단위p47phox함량、PARP활성급표체.결과:고갑류안산음식유도ApoE-/-소서산생Hhcy,촉진양화응격상관p47phox표체급PARP활화,현저증가반괴면적;PARP억제제3-AB수연대보식조ApoE-/-소서억제효과불명현,각능재불영향혈장Hcy화지질함량적정황하,억제Hhcy유도적PARP활화,현저강저기죽양반괴면적체40%.결론:PARP억제제3-AB현저강저Hhcy유도적ApoE-/-소서동맥죽양경화반괴면적,가작위유효억제죽양반괴진정적치료방법지일.
Objectives:To explore whether Poly (ADP-ribose) polymerase (PARP) inhibitor 3-aminobenzamide (3-AB) decreases the atherosclerotic plaque size in an hyperhomocysteinemia (Hhcy)-induced experimental model with atherosclerosis. Methods:Six-week-old homozygous apolipoprotein E-deficient (ApoE-/-) male mice fed with normal diet or high methionine-diet were randomly received intraperitoneal injections of 10 mg/kg 3-AB dissolved in PBS, or physiological saline every other day for 12 weeks. Plasma homocysteine (Hcy) levels and lipids contents were measured. Atherosclerotic lesion sizes, the phosphorylation of p47phox subunit of NADPH oxidase and the expression of PARP protein and PARP activity were detected. Results:ApoE-/- mice fed with high methionine-diet generated Hhcy, which could promote the oxidative stress-associated the phosphorylation of p47phox and PARP activation, and increase the atherosclerotic lesion size significantly. Although PARP inhibition by 3-AB did not markedly inhibit the plaque development in ApoE-/- mice with spontaneous hyperlipidemia fed with normal diet, it significantly reduced atherosclerotic lesion size by 40% in Hhcy-induced atherosclerosis without affecting plasma homocysteine levels and lipid contents, effectively suppressed the PARP activation. Conclusions:Our results suggest that PARP inhibition attenuates the atherosclerotic plaque size in the hyperhomocysteinemic conditions, indicates 3-AB may prove beneficial for the treatment of atherosclerosis.
