中国循证心血管医学杂志
中國循證心血管醫學雜誌
중국순증심혈관의학잡지
CHINESE JOURNAL OF EVIDENCE-BASES CARDIOVASCULAR MEDICINE
2015年
1期
72-76
,共5页
炎症信号通路%血管重构%单核细胞趋化蛋白1%过氧化物酶体增殖物活化受体γ%血管损伤%小鼠
炎癥信號通路%血管重構%單覈細胞趨化蛋白1%過氧化物酶體增殖物活化受體γ%血管損傷%小鼠
염증신호통로%혈관중구%단핵세포추화단백1%과양화물매체증식물활화수체γ%혈관손상%소서
Inflammatory signal pathway%Vascular remodeling%Monocyte chemoattractant protein-1%Peroxisome proliferator-activated receptor-γ%Vascular injury%mice
目的:观察厄贝沙坦联合瑞舒伐他汀对血管损伤小鼠血管重构的影响。方法8周龄C57BL/6野生型雄性小鼠50只,随机分成5组:假手术组、手术组、厄贝沙坦治疗组(50 mg/kg·d)、瑞舒伐他汀治疗组(5 mg/kg·d)、厄贝沙坦(0.5 mg/kg·d)联合瑞舒伐他汀治疗组(2 mg/kg·d),每组10只。手术使用套管制作股动脉损伤模型。连续灌胃给药14 d后处死小鼠。留取小鼠股动脉标本,分别采用HE染色及NIH图像分析软件测量血管内膜面积,RT-PCR法检测MCP-1、CCR2及PPARγmRNA表达水平。各组小鼠检测实验前后血脂及肝功能指标。结果假手术组(0μm2)未见血管内膜增生。新生内膜面积手术组(6497±5.7)μm2、厄贝沙坦治疗组(5979±1.4)μm2、瑞舒伐他汀治疗组(6005±5.8)μm2、厄贝沙坦联合瑞舒伐他汀治疗组(2269±2.8)μm2,均有新生内膜形成,与假手术组比较有统计学差异(P均<0.05)。与手术组比较,厄贝沙坦治疗组、瑞舒伐他汀治疗组新生内膜面积差异无统计学意义(P均>0.05)。与手术组、厄贝沙坦治疗组、瑞舒伐他汀治疗组比较,厄贝沙坦联合瑞舒伐他汀治疗组内膜增生面积降低,差异有统计学意义(P均<0.05)。MCP-1 mRNA相对表达量:与假手术组比较,手术组、厄贝沙坦治疗组、瑞舒伐他汀治疗组、厄贝沙坦联合瑞舒伐他汀治疗组相对表达量增加,差异有统计学意义(P均<0.05)。与手术组、厄贝沙坦治疗组、瑞舒伐他汀治疗组比较,厄贝沙坦联合瑞舒伐他汀治疗组相对表达量降低,差异有统计学意义(P均<0.05)。CCR2 mRNA相对表达量:与假手术组比较,手术组、厄贝沙坦治疗组、瑞舒伐他汀治疗组、厄贝沙坦联合瑞舒伐他汀治疗组增加,差异有统计学意义(P均<0.05)。PPARγmRNA相对表达量:与假手术组比较,手术组、厄贝沙坦治疗组、瑞舒伐他汀治疗组、厄贝沙坦联合瑞舒伐他汀治疗组相对表达量降低,差异有统计学意义(P均<0.05)。与手术组、厄贝沙坦治疗组、瑞舒伐他汀治疗组比较,厄贝沙坦联合瑞舒伐他汀治疗组相对表达量增加,差异有统计学意义(P均<0.05)。MCP-1 mRNA相对表达量与PPARγ相对表达量呈负相关(r=-0.607,P<0.05)。结论厄贝沙坦联合瑞舒伐他汀可能通过增加PPARγ表达,降低MCP-1表达,延缓损伤血管的重构。
目的:觀察阨貝沙坦聯閤瑞舒伐他汀對血管損傷小鼠血管重構的影響。方法8週齡C57BL/6野生型雄性小鼠50隻,隨機分成5組:假手術組、手術組、阨貝沙坦治療組(50 mg/kg·d)、瑞舒伐他汀治療組(5 mg/kg·d)、阨貝沙坦(0.5 mg/kg·d)聯閤瑞舒伐他汀治療組(2 mg/kg·d),每組10隻。手術使用套管製作股動脈損傷模型。連續灌胃給藥14 d後處死小鼠。留取小鼠股動脈標本,分彆採用HE染色及NIH圖像分析軟件測量血管內膜麵積,RT-PCR法檢測MCP-1、CCR2及PPARγmRNA錶達水平。各組小鼠檢測實驗前後血脂及肝功能指標。結果假手術組(0μm2)未見血管內膜增生。新生內膜麵積手術組(6497±5.7)μm2、阨貝沙坦治療組(5979±1.4)μm2、瑞舒伐他汀治療組(6005±5.8)μm2、阨貝沙坦聯閤瑞舒伐他汀治療組(2269±2.8)μm2,均有新生內膜形成,與假手術組比較有統計學差異(P均<0.05)。與手術組比較,阨貝沙坦治療組、瑞舒伐他汀治療組新生內膜麵積差異無統計學意義(P均>0.05)。與手術組、阨貝沙坦治療組、瑞舒伐他汀治療組比較,阨貝沙坦聯閤瑞舒伐他汀治療組內膜增生麵積降低,差異有統計學意義(P均<0.05)。MCP-1 mRNA相對錶達量:與假手術組比較,手術組、阨貝沙坦治療組、瑞舒伐他汀治療組、阨貝沙坦聯閤瑞舒伐他汀治療組相對錶達量增加,差異有統計學意義(P均<0.05)。與手術組、阨貝沙坦治療組、瑞舒伐他汀治療組比較,阨貝沙坦聯閤瑞舒伐他汀治療組相對錶達量降低,差異有統計學意義(P均<0.05)。CCR2 mRNA相對錶達量:與假手術組比較,手術組、阨貝沙坦治療組、瑞舒伐他汀治療組、阨貝沙坦聯閤瑞舒伐他汀治療組增加,差異有統計學意義(P均<0.05)。PPARγmRNA相對錶達量:與假手術組比較,手術組、阨貝沙坦治療組、瑞舒伐他汀治療組、阨貝沙坦聯閤瑞舒伐他汀治療組相對錶達量降低,差異有統計學意義(P均<0.05)。與手術組、阨貝沙坦治療組、瑞舒伐他汀治療組比較,阨貝沙坦聯閤瑞舒伐他汀治療組相對錶達量增加,差異有統計學意義(P均<0.05)。MCP-1 mRNA相對錶達量與PPARγ相對錶達量呈負相關(r=-0.607,P<0.05)。結論阨貝沙坦聯閤瑞舒伐他汀可能通過增加PPARγ錶達,降低MCP-1錶達,延緩損傷血管的重構。
목적:관찰액패사탄연합서서벌타정대혈관손상소서혈관중구적영향。방법8주령C57BL/6야생형웅성소서50지,수궤분성5조:가수술조、수술조、액패사탄치료조(50 mg/kg·d)、서서벌타정치료조(5 mg/kg·d)、액패사탄(0.5 mg/kg·d)연합서서벌타정치료조(2 mg/kg·d),매조10지。수술사용투관제작고동맥손상모형。련속관위급약14 d후처사소서。류취소서고동맥표본,분별채용HE염색급NIH도상분석연건측량혈관내막면적,RT-PCR법검측MCP-1、CCR2급PPARγmRNA표체수평。각조소서검측실험전후혈지급간공능지표。결과가수술조(0μm2)미견혈관내막증생。신생내막면적수술조(6497±5.7)μm2、액패사탄치료조(5979±1.4)μm2、서서벌타정치료조(6005±5.8)μm2、액패사탄연합서서벌타정치료조(2269±2.8)μm2,균유신생내막형성,여가수술조비교유통계학차이(P균<0.05)。여수술조비교,액패사탄치료조、서서벌타정치료조신생내막면적차이무통계학의의(P균>0.05)。여수술조、액패사탄치료조、서서벌타정치료조비교,액패사탄연합서서벌타정치료조내막증생면적강저,차이유통계학의의(P균<0.05)。MCP-1 mRNA상대표체량:여가수술조비교,수술조、액패사탄치료조、서서벌타정치료조、액패사탄연합서서벌타정치료조상대표체량증가,차이유통계학의의(P균<0.05)。여수술조、액패사탄치료조、서서벌타정치료조비교,액패사탄연합서서벌타정치료조상대표체량강저,차이유통계학의의(P균<0.05)。CCR2 mRNA상대표체량:여가수술조비교,수술조、액패사탄치료조、서서벌타정치료조、액패사탄연합서서벌타정치료조증가,차이유통계학의의(P균<0.05)。PPARγmRNA상대표체량:여가수술조비교,수술조、액패사탄치료조、서서벌타정치료조、액패사탄연합서서벌타정치료조상대표체량강저,차이유통계학의의(P균<0.05)。여수술조、액패사탄치료조、서서벌타정치료조비교,액패사탄연합서서벌타정치료조상대표체량증가,차이유통계학의의(P균<0.05)。MCP-1 mRNA상대표체량여PPARγ상대표체량정부상관(r=-0.607,P<0.05)。결론액패사탄연합서서벌타정가능통과증가PPARγ표체,강저MCP-1표체,연완손상혈관적중구。
Objective To observe the influence of irbesartan combining rosuvastatin on vascular remodeling in mice with vascular injury. Methods Male C57BL/6 wild mice (n=50, 8 weeks old) were randomly divided into sham-operation group, operation group, irbesartan group (50 mg/kg·d), rosuvastatin group (5 mg/kg·d), irbesartan (0.5 mg/kg·d)+rosuvastatin (2 mg/kg·d) group (each n=10). The model of femoral artery injury was established by using cannula. After 14-day intragastrical medication, the mice were executed and femoral samples were collected. The intima area was measured by using HE staining and NIH image analysis software, and expressions of MCP-1 mRNA, CCR2 mRNA and PPARγmRNA were detected by using RT-PCR. The indexes of blood fat and liver function were detected in all groups before and after treatment. Results There was no intima hyperplasia in sham-operation group (0μm2). There were neointima formation in operation group (6497±5.7)μm2, irbesartan group (5979±1.4)μm2, rosuvastatin group (6005±5.8)μm2 and irbesartan+rosuvastatin group (2269±2.8)μm2 compared with sham-operation group (all P<0.05). The difference in intima hyperplasia area had no statistical significance between operation group and irbesartan group or rosuvastatin group (all P>0.05). The intima hyperplasia area decreased in irbesartan+rosuvastatin group compared with operation group, irbesartan group and rosuvastatin group (all P<0.05). The expression of MCP-1 mRNA increased in operation group, irbesartan group, rosuvastatin group and irbesartan+rosuvastatin group compared with sham-operation group (all P<0.05), and decreased in irbesartan+rosuvastatin group compared with operation group, irbesartan group and rosuvastatin group (all P<0.05). The expression of CCR2 mRNA increased in operation group, irbesartan group, rosuvastatin group and irbesartan+rosuvastatin group compared with sham-operation group (all P<0.05). The expression of PPARγmRNA decreased in operation group, irbesartan group, rosuvastatin group and irbesartan+rosuvastatin group compared with sham-operation group (all P<0.05), and increased in irbesartan+rosuvastatin group compared with operation group, irbesartan group and rosuvastatin group (all P<0.05). The expression of MCP-1 mRNA was negatively correlated to the expression of PPARγmRNA (r=-0.607, P<0.05). Conclusion Irbesartan combining rosuvastatin can reduce the expression of MCP-1 mRNA and delay remodeling of injured vessel through increase the expression of PPARγmRNA.