国际脑血管病杂志
國際腦血管病雜誌
국제뇌혈관병잡지
INTERNATIONAL JOURNAL OF CEREBROVASCULAR DISEASES
2014年
5期
381-386
,共6页
动脉粥样硬化%主动脉%白细胞介素-10%白细胞介素-17%基质金属蛋白酶12%炎症%高胆固醇血症%兔
動脈粥樣硬化%主動脈%白細胞介素-10%白細胞介素-17%基質金屬蛋白酶12%炎癥%高膽固醇血癥%兔
동맥죽양경화%주동맥%백세포개소-10%백세포개소-17%기질금속단백매12%염증%고담고순혈증%토
Atherosclerosis%Aorta%Interleukin-10%Interleukin-17%Matrix Metalloproteinase 12%Inflammation%Hypercholesterolemia%Rabbits
目的 探讨白细胞介素(interleukin,IL)-17、IL-10和基质金属蛋白酶(matrix metalloproteinase,MMP)-12在动脉粥样硬化发病机制中的作用,并进一步了解阿托伐他汀对动脉粥样硬化的干预机制.方法 18只日本大耳白兔,随机分为正常对照组、模型组和干预组,每组6只.对照组喂食基础饲料,模型组喂食高脂饲料,干预组喂食高脂饲料加阿托伐他汀5 mg/(kg·d),饲养时间均为12周.采用酶比色法检测血清总胆固醇(total cholesterol,TC)和三酰甘油(triglyceride,TG)水平,采用选择性沉淀法测定血清低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)和高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDL-C)水平,采用双抗体夹心酶联免疫吸附法测定血清IL-17、IL-10和MMP-12水平.HE染色观察动脉粥样硬化斑块病理形态学变化,应用图像分析软件计算内膜厚度、内膜/中膜比、斑块面积及斑块比例.结果 干预组血清TC、TG、LDL-C水平以及IL-17和MMP-12表达水平均显著性低于模型组(P均＜0.05),但仍略高于对照组(P＜0.05),HDL-C水平无显著性差异.干预组血清IL-10水平均显著性高于对照组和模型组(P均＜0.05).干预组内膜厚度、内膜/中膜比、斑块面积和斑块比例均较模型组显著性降低(P均＜0.05).相关分析显示,斑块比例与IL-17(r =0.847,P=0.001)和MMP-12(r=0.839,P=0.001)均呈显著正相关,与IL-10呈显著负相关(r=-0.794,P=0.002);IL-17与MMP-12呈显著正相关(r=0.709,P =0.001),与IL-10呈显著负相关(r=-0.738,P＜0.001),MMP-12与IL-10水平呈显著负相关(r=-0.563,P=0.015).结论 IL-17和MMP-12水平增高以及IL-10水平降低说明炎性因子在动脉粥样硬化的发病机制中起着重要的病理学作用.阿托伐他汀除降脂作用外,还可能通过减少IL-17和MMP-12以及增加IL-10的表达,降低动脉慢性炎症反应程度而发挥抗动脉粥样硬化作用.
目的 探討白細胞介素(interleukin,IL)-17、IL-10和基質金屬蛋白酶(matrix metalloproteinase,MMP)-12在動脈粥樣硬化髮病機製中的作用,併進一步瞭解阿託伐他汀對動脈粥樣硬化的榦預機製.方法 18隻日本大耳白兔,隨機分為正常對照組、模型組和榦預組,每組6隻.對照組餵食基礎飼料,模型組餵食高脂飼料,榦預組餵食高脂飼料加阿託伐他汀5 mg/(kg·d),飼養時間均為12週.採用酶比色法檢測血清總膽固醇(total cholesterol,TC)和三酰甘油(triglyceride,TG)水平,採用選擇性沉澱法測定血清低密度脂蛋白膽固醇(low-density lipoprotein cholesterol,LDL-C)和高密度脂蛋白膽固醇(high-density lipoprotein cholesterol,HDL-C)水平,採用雙抗體夾心酶聯免疫吸附法測定血清IL-17、IL-10和MMP-12水平.HE染色觀察動脈粥樣硬化斑塊病理形態學變化,應用圖像分析軟件計算內膜厚度、內膜/中膜比、斑塊麵積及斑塊比例.結果 榦預組血清TC、TG、LDL-C水平以及IL-17和MMP-12錶達水平均顯著性低于模型組(P均＜0.05),但仍略高于對照組(P＜0.05),HDL-C水平無顯著性差異.榦預組血清IL-10水平均顯著性高于對照組和模型組(P均＜0.05).榦預組內膜厚度、內膜/中膜比、斑塊麵積和斑塊比例均較模型組顯著性降低(P均＜0.05).相關分析顯示,斑塊比例與IL-17(r =0.847,P=0.001)和MMP-12(r=0.839,P=0.001)均呈顯著正相關,與IL-10呈顯著負相關(r=-0.794,P=0.002);IL-17與MMP-12呈顯著正相關(r=0.709,P =0.001),與IL-10呈顯著負相關(r=-0.738,P＜0.001),MMP-12與IL-10水平呈顯著負相關(r=-0.563,P=0.015).結論 IL-17和MMP-12水平增高以及IL-10水平降低說明炎性因子在動脈粥樣硬化的髮病機製中起著重要的病理學作用.阿託伐他汀除降脂作用外,還可能通過減少IL-17和MMP-12以及增加IL-10的錶達,降低動脈慢性炎癥反應程度而髮揮抗動脈粥樣硬化作用.
목적 탐토백세포개소(interleukin,IL)-17、IL-10화기질금속단백매(matrix metalloproteinase,MMP)-12재동맥죽양경화발병궤제중적작용,병진일보료해아탁벌타정대동맥죽양경화적간예궤제.방법 18지일본대이백토,수궤분위정상대조조、모형조화간예조,매조6지.대조조위식기출사료,모형조위식고지사료,간예조위식고지사료가아탁벌타정5 mg/(kg·d),사양시간균위12주.채용매비색법검측혈청총담고순(total cholesterol,TC)화삼선감유(triglyceride,TG)수평,채용선택성침정법측정혈청저밀도지단백담고순(low-density lipoprotein cholesterol,LDL-C)화고밀도지단백담고순(high-density lipoprotein cholesterol,HDL-C)수평,채용쌍항체협심매련면역흡부법측정혈청IL-17、IL-10화MMP-12수평.HE염색관찰동맥죽양경화반괴병리형태학변화,응용도상분석연건계산내막후도、내막/중막비、반괴면적급반괴비례.결과 간예조혈청TC、TG、LDL-C수평이급IL-17화MMP-12표체수평균현저성저우모형조(P균＜0.05),단잉략고우대조조(P＜0.05),HDL-C수평무현저성차이.간예조혈청IL-10수평균현저성고우대조조화모형조(P균＜0.05).간예조내막후도、내막/중막비、반괴면적화반괴비례균교모형조현저성강저(P균＜0.05).상관분석현시,반괴비례여IL-17(r =0.847,P=0.001)화MMP-12(r=0.839,P=0.001)균정현저정상관,여IL-10정현저부상관(r=-0.794,P=0.002);IL-17여MMP-12정현저정상관(r=0.709,P =0.001),여IL-10정현저부상관(r=-0.738,P＜0.001),MMP-12여IL-10수평정현저부상관(r=-0.563,P=0.015).결론 IL-17화MMP-12수평증고이급IL-10수평강저설명염성인자재동맥죽양경화적발병궤제중기착중요적병이학작용.아탁벌타정제강지작용외,환가능통과감소IL-17화MMP-12이급증가IL-10적표체,강저동맥만성염증반응정도이발휘항동맥죽양경화작용.
Objective To investigate the roles of interleuldn (IL)-17,IL-10,and matrix metalloproteinase12 (MMP-12) in the pathogenesis of atherosclerosis and further to understand the intervention mechanism of atorvastatin for atherosclerosis.Methods Eighteen Japanese white rabbits were randomly divided into 3 groups:control,model and intervention groups (n =6 in each group).The control group,model group and intervention group were fed basic diet,high-fat diet,and high-fat diet plus atorvastatin (5 mg/(kg·d),respectively for 12 weeks.The levels of serum total cholesterol (TC) and triglyceride (TG) were determined by enzymatic colorimetric method; the levels of low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were determined by selective precipitation method; the levels of IL-17,IL-10,and MMP-12 were measured by double antibody sandwich enzyme-linked immunosorbent assay (ELISA); the pathological morphology changes of atherosclerotic plaque was observe by HE staining; and the thickness of the intima,intima/media ratio,plaque area,and plaque proportion were calculated by image analysis software.Results The expression levels of serum TC,TG,LDL-C,and IL-17,as well as those of IL-17 and MMP-12 of the intervention group were significantly lower than those of the model group (all P ＜0.05),but they were still higher than the control group (all P ＜0.05),while there was no significant difference in the level of HDL-C.The level of serum IL-10 of the intervention group was higher than that of the model group and the control group (all P＜0.05).The thickness of intima,intima/media ratio,plaque area,and plaque proportion of the intervention group were all significantly lower than those of the model group (all P ＜0.05).Correlation analysis showed that the plaque proportion was significantly positively correlated with IL-17 (r =0.847,P =0.001) and MMP-12 (r =0.839,P =0.001),and was negatively correlated with IL-10 (r =0.794,P =0.002); IL-17 was significantly positively correlated with MMP-12 (r =0.709,P=0.001),and was significantly negatively correlated with IL-10 (r =0.738,P＜0.001).MMP-12 was significantly negatively correlated with IL-10 (r =0.563,P =0.015).Conclusion The increased levels of IL-17 and MMP-12,as well as the decreased level of IL-10 illustrate that inflammatory factors play an important pathological role in the pathogenesis of atherosclerosis.In addition to lipid-lowering effect,atorvastatin may decrease the degree of chronic arterial inflammatory response and play a role in anti-atherosclerosis by decreasing the expression of IL-17 and MMP-12,as well as increasing the expression of IL-10.
