CAJ | 학술논문

目的探讨瘦素是否影响动脉内膜的增生及其发生机制.方法利用野生型(Wt)、瘦素基因缺陷(Lep-/-)、瘦素受体基冈缺陷(LepR-/-)小鼠,通过股动脉内膜损伤及瘦素疗法,结合组织学特性,分析瘦素影响动脉内膜增生情况及其机制.结果动脉内膜损伤后4周,Lep-/-和LepR-/-小鼠的内膜面积与中层面积比值(I/M)均小于Wt小鼠,差异均有统计学意义(Lep-/-小鼠比Wt小鼠为0.80±0.14比1.50±0.22,P<0.01;LepR-/-小鼠比Wt小鼠为0.55±0.20比1.50 ±0.22,P<0.05).Lep-/-和LepR-/-小鼠经动脉内膜损伤并同时给予瘦素治疗后,前者的I/M显著增加,而后者的I/M无明显变化.α-肌动蛋白和5-溴-2-脱氧尿嘧啶染色显示,二者在各组动脉增生内膜的阳性率分布趋势与内膜增厚程度一致.结论瘦素缺乏或瘦素受体缺乏防止动脉内膜增生,外源性瘦素恢复Lep-/-小鼠动脉内膜增生,但对LepR-/-小鼠内膜无影响.本研究从动物模型上证明,高瘦素血症是动脉内膜增生的高危因素,并说明瘦素通过瘦素受体刺激血管平滑肌细胞增殖而促进动脉内膜增生.
목적 탐토수소시부영향동맥내막적증생급기발생궤제.방법 이용야생형(Wt)、수소기인결함(Lep-/-)、수소수체기강결함(LepR-/-)소서,통과고동맥내막손상급수소요법,결합조직학특성,분석수소영향동맥내막증생정황급기궤제.결과 동맥내막손상후4주,Lep-/-화LepR-/-소서적내막면적여중층면적비치(I/M)균소우Wt소서,차이균유통계학의의(Lep-/-소서비Wt소서위0.80±0.14비1.50±0.22,P<0.01;LepR-/-소서비Wt소서위0.55±0.20비1.50 ±0.22,P<0.05).Lep-/-화LepR-/-소서경동맥내막손상병동시급여수소치료후,전자적I/M현저증가,이후자적I/M무명현변화.α-기동단백화5-추-2-탈양뇨밀정염색현시,이자재각조동맥증생내막적양성솔분포추세여내막증후정도일치.결론 수소결핍혹수소수체결핍방지동맥내막증생,외원성수소회복Lep-/-소서동맥내막증생,단대LepR-/-소서내막무영향.본연구종동물모형상증명,고수소혈증시동맥내막증생적고위인소,병설명수소통과수소수체자격혈관평활기세포증식이촉진동맥내막증생.
Objective To evaluate the role of leptin in neointimal formation and related mechanisms.Methods Femoral arterial injury was induced in wild-type (Wt,n = 10),leptin-deficient (Lep -/-,n = 12),and ieptin receptor-deficient (LepR -/- ,n = 10) mice.Leptin treatment studies (tail vein injection of adenovirus expressing murine ieptin on the RSV promoter,ad-leptin) were performed on Lep -/- (n = 5) and LepR -/- (n = 4) mice.Intimal (I) and medial (M) areas were measured and the ratio of I/M was calculated.Smooth muscle cells were detected by smooth muscle α-actin staining using an α-actin monoclonal antibody.Cellular proliferation was analyzed with BrdU Staining Kit and the number of BrdU-positive cells was counted manually.Plasma leptin level was measured by ELISA.Results The I/M ratio of Lep -/- and LepR -/- mice was significantly lower than that in Wt separately (Lep -/- vs.Wt = 0.80±0.14 vs.1.50±0.22,P<0.01; LepR-/- vs.Wt=0.55±0.20 vs.1.50±0.22,P<0.05).Plasma leptin level was significantly increased in Lep-/- and LepR -/- mice post leptin treatment.I/M was significantly increased in Lep -/- mice receiving ad-leptin compared with untreated Lep -/- mice (P < 0.05),while I/M was similar between LepR -/- mice with and without ad-leptin treatment (P > 0.05).The changes on number of positive α-actin and BrdU stained smooth muscle cells were consistent with the neointimal formation findings in various groups.Conclusions Mice lacking leptin or the ieptin receptor were protected from neointimal formation following vascular injury.Leptin treatment increased neointimsl formation in Lep-/- but not in LepR-/- mice,suggesting leptin receptor activation and vascular smooth muscle cell proliferation played a pivotal role on neointimal formation post-injury in this model,giving an evidence that high plasma leptin level is a risk factor for neointimal formation.