椎基底动脉延长扩张症大鼠JNK、MMP-9和MAC387的表达及瑞舒伐他汀的干预作用

Expressions of c-Jun N-terminal kinase,matrix metalloproteinase-9 and macrophage marker MAC387 in rats with vertebrobasilar dolichoectasia and intervention effect of rosuvastatin

目的观察椎基底动脉延长扩张症(VBD)大鼠血管中c-Jun氨基末端激酶(JNK)、基质金属蛋白酶-9(MMP-9)和巨噬细胞标志物MAC387表达的变化,探讨瑞舒伐他汀对VBD的治疗作用及机制。方法将60只SD大鼠按随机数字法机分为3组:假手术组、VBD模型组和瑞舒伐他汀干预组,每组20只。后2组大鼠通过枕大池注入0.3μL(1.5 U/μL)弹性蛋白酶以制备VBD模型,假手术组大鼠注入等量生理盐水。造模后24 h瑞舒伐他汀干预组大鼠给予5 mg/kg瑞舒伐他汀灌胃,1次/d,连续4周,其余2组大鼠每天给予等量蒸馏水灌胃。测量并比较各组大鼠的椎基底动脉弯曲扩张程度,采用Western blotting和免疫荧光染色分别检测椎基底动脉中JNK、MMP-9和MAC387的表达。结果瑞舒伐他汀干预组、VBD模型组均有14只大鼠造模成功。与假手术组比较,VBD模型组、瑞舒伐他汀干预组大鼠的基底动脉直径增加,基底动脉迂曲指数增加,差异均有统计学意义(P<0.05)。与假手术组相比,VBD模型组、瑞舒伐他汀干预组大鼠椎基底动脉中JNK、MMP-9、MAC387的表达均增多,差异均有统计学意义(P<0.05);与VBD模型组相比,瑞舒伐他汀干预组大鼠椎基底动脉中JNK、MMP-9、MAC387的表达均减少,差异均有统计学意义(P<0.05)。结论瑞舒伐他汀可延缓VBD的进展,其机制可能与抑制炎症反应有关。

Objective To observe the expressions of c-Jun N-terminal kinase(JNK),matrix metalloproteinase-9(MMP-9)and macrophage marker MAC387 in the blood vessels of rats with vertebrobasilar dolichoectasia(VBD),and to study the therapeutic effect and mechanism of rosuvastatin on VBD.Methods Sixty male SD rats were randomly divided into sham-operated group,VBD model group and rosuvastatin intervention group(n=20).Elastase at 0.3 uL(1.5 U/μL)was injected into the cisterna magna of rats in the latter two groups to establish VBD models;while same volume of saline solution was given to rats in the sham-operated group.Twenty-four h after model making,5 mg/(kg.d)rosuvastatin(once/d,for 4 weeks)was administered intragastrically into rats in the rosuvastatin intervention group,and same volume of distilled water was administered intragastrically into rats in the other 2 groups.The degrees of extension and expansion of vertebrobasilar artery were measured and compared among the 3 groups.Western blotting was used to detect the expressions of JNK and MMP-9,and immunofluorescent staining was used to detect the MAC387 expression in the vertebrobasilar artery.Results Fourteen rats in the VBD model group and rosuvastatin intervention group,respectively,had successful model making.As compared with the sham-operated group,the VBD model group and rosuvastatin intervention group had statistically increased basilar artery diameter and basilar artery tortuosity index(P<0.05).The expressions of JNK,MMP-9 and MAC387 in the VBD model group and rosuvastatin intervention group were significantly increased as compared with those in the sham-operated group(P<0.05);as compared with those in the VBD model group,the expressions of JNK,MMP-9 and MAC387 in the vertebrobasilar artery of rosuvastatin intervention group were significantly decreased(P<0.05).Conclusion Rosuvastatin can delay VBD progress,whose mechanism may be related to the inhibition of inflammatory response.