核因子-κB特异性抑制剂小白菊内酯在大鼠心肌组织的药效时间

The action time of parthenolide as selective nuclear factor-κB inhibitor in heart of rats

目的观察核因子-κB(NF-κB)特异性抑制剂小白菊内酯(PTN)在大鼠心肌组织中的药效作用时间。方法健康雄性SD大鼠40只随机分为5组:空白对照组、PTN组、二甲亚砜(DMSO)组、脂多糖(LPS)组和PTN+LPS组。第1天:PTN组、DMSO组和PTN+LPS组大鼠分别腹腔内注射PTN(500μg/kg)和PTN溶剂DMSO(相等容量);其余各组腹腔内注射相等容量的生理盐水。第2天(即PTN注射后24 h):LPS组和PTN+LPS组大鼠经皮下注射LPS(12.5 mg/kg);其余各组经皮下注射相等容量的生理盐水。每组在相当于注射LPS后1 h时取出心脏,采用Westernblot法分析心肌细胞细胞核内NF-κB p50和细胞浆中抑制蛋白(IκBα)、磷酸化抑制蛋白(p-IκBα)表达变化。结果与空白对照相比,PTN组和DMSO组NF-κB p50I、κBα和p-IκBα表达差异无统计学意义,而LPS组和PTN+LPS组NF-κBp50表达上调(P<0.05),IκBα表达下调(P<0.05),p-IκBα表达上调(P<0.05)。结论LPS刺激可在1 h内激活NF-κB,PTN(500μg/kg)在大鼠体内代谢24 h后未见明显药效。

Purpose To observe the action time of parthenolide （PTN） as selective nuclear factor-κB（NF- κB） inhibitor in heart of rats. Methods Forty SD rats were randomly divided into control（CON） group,PTN group, dimethyl sutfoxide（DMSO） group, lipopolysaccharide（LPS） group and PTN ＋ LPS group. The first day： PTN group, DMSO group and PTN ＋ LPS group rats were respectively injected interapertoneally PTN（500 μg/ kg） and DMSO; other groups rats were injected interapertoneally equivalent saline.The second day（in equivalent to 24 h after injecting PTN） ：in LPS group and PTN ＋ LPS group LPS（12.5 mg/kg） was administered subcutaneously ; other group rats were injected subcutaneously equivalent saline. Every heart was obtained in equivalentce to 1 h after injecting LPS to measure the expression of NF-κB p50 in nucleus, inhibitory kappaB （IκBα） and phosphorylation inhibitory kappaB（p-IκBα） in cytoplasm of cardiac myocytes through Western blotting. Results Compared with CON group, the expression of NF-κB p50, IκBα and p-IκBα had no difference in PTN and DMSO group. And in LPS group and PTN ＋ LPS group,the expression of NF-κB p50 up-regulated significantly（ P 〈 0. 05）, IκBα down-regulated（ P 〈 0.05 ） and p-IκBα up-regulated significantly （ P 〈 0.05 ）. Conclusion LPS can activate NF-κB in 1 h and PTN in rats after 24 h has few effect.