摘要
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PPARγm RNA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 m RNA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 m RNA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)。PPARγm RNA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 m RNA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。
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 randomiy 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 eannula. 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 imageanalysis software, and expressions of MCP-1 mRNA, CCR2 mRNA and PPAR y mRNA 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 （0 μ m2）. There were neointima formation in operation group （6497 ±5.7） μ m2, irbesartan group （5979± 1,4） μ m2, rosuvastatin group （6005± 5.8） μ m2 and irbesartan＋rosuvastatin group （2269 ± 2.8） μ m2 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＋rosuvastatln group compared with operation group, irbesartan group and rosuvastatin group （all P〈0.05）. The expression of MCP-1 mRNA increased in operation gro/ip, 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 PPAR y mRNA 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 PPAR y mRNA （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 PPAR y mRNA.
出处
《中国循证心血管医学杂志》
2015年第1期72-76,共5页
Chinese Journal of Evidence-Based Cardiovascular Medicine
关键词
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
Inflammatory signal pathway
Vascular remodeling
Monocyte chemoattractant protein-l
Peroxisome proliferator-activated receptor- y
Vascular injury
mice
