小白菊内酯对球囊损伤后新生内膜增殖的影响

Effect of parthenolide on neointimal hyperplasia after balloon injury

目的：研究小白菊内酯（PN）对球囊损伤（balloon injury,BI）后新生内膜的影响及机制。方法：将30只雄性新西兰兔2.0~2.3 kg在高脂适应性喂养1周后随机分为6组：假手术＋生理盐水（sham＋NS）组;假手术＋二甲基亚砜（sham＋DMSO）组;球囊损伤＋生理盐水（BI＋NS）组;球囊损伤＋DMSO（BI＋DMSO）组;球囊损伤＋PN低剂量（BI＋PN low）组;球囊损伤＋PN高剂量（BI＋PN high）组。PN溶解于DMSO,术后立即按分组腹腔注射同体积药物治疗,每日1次。继续高脂喂养4周后取血清及髂总动脉,分析比较血管内-中膜厚度、半胱氨酰天冬氨酸蛋白酶（caspase）-1、白细胞介素（IL）-1β和IL-8的表达量以及血清总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白（LDL）和高密度脂蛋白（HDL）的含量。结果：BI＋DMSO组较sham＋DMSO组内膜厚度、caspase-1、IL-1β和IL-8的表达量增加（P〈0.05）;与BI＋DMSO组比较,上述指标在PN高、低剂量组有不同程度降低,但仅PN高剂量组与其差异有统计学意义（P〈0.05）;各组血脂指标差异不明显。结论：PN能抑制球囊损伤后的内膜增殖,其机制可能与抗炎作用有关。

AIM： To detect the effect and underlying mechanism of parthenolide（ PN） on neointimal hyperplasia. METHODS： After 1 week of high-fat feeding,30 male New Zealand white rabbits（ 2. 0 ~ 2. 3 kg） were randomly divided into 6 groups： sham ＋ NS,rabbits received 0. 9% normal saline after sham operation; sham ＋ DMSO,rabbits received DMSO after sham operation; balloon injury（ BI） ＋ NS,rabbits received NS after balloon injury; BI ＋ DMSO,rabbits received DMSO after balloon injury; BI ＋ PN low,rabbits received PN at 1 mg / kg after balloon injury; BI ＋ PN high,rabbits received PN at 2 mg / kg after balloon injury. The drugs were intraperitoneal injected once a day after the operation until sacrifice. After fed with high-fat diet for 4 weeks,the intima-media thickness,the expression of caspase-1,IL-1β,the levels of IL-8,TC,TG,LDL and HDL in the serum were measured. RESULTS： Compared with sham ＋ DMSO group,the thickness of intima,the amount of caspase-1,IL-1β and IL-8 in BI ＋ DMSO group were significantly increased（ P〈0. 05）. The levels of caspase-1,IL-1β and IL-8 were significantly decreased in BI ＋ PN high group compared with BI ＋DMSO group（ P〈0. 05）. CONCLUSION： Neointimal hyperplasia is suppressed by PN after balloon injury,the potential mechanism may be associated with its anti-inflammatory role.