淫羊藿次苷Ⅱ通过下调ERK1/2-NF-κB信号通路抗野百合碱所致大鼠肺动脉重构

IcarisideⅡprevents monocrotaline-induced pulmonary artery remodeling by decreasing the ERK1/2-NF-κB signaling pathway in rats

目的研究淫羊藿次苷Ⅱ(ICSⅡ)对野百合碱(MCT)所致大鼠肺动脉重构的作用,并探讨其对ERK1/2-NF-κB信号通路的影响。方法 SD大鼠随机分为对照组(Control)、ICS II单纯给药组(Control+ICSⅡ-H,16 mg/kg)、模型组(Model)、ICS II低、中、高剂量组(ICS II-L、ICS II-M、ICS II-H,4、8、16 mg/kg),每组6只。Model组和ICSⅡ低、中、高剂量组经颈背部一次性皮下注射MCT(50 mg/kg)诱导肺动脉重构模型。造模后第1天开始给药至第28天结束。H&E染色观察肺小动脉病理改变;免疫组织化学法检测肺小动脉PCNA、p-ERK1/2、p-NF-κB蛋白的表达。结果与Control组比较,Model组肺小动脉中膜明显肥厚;PCNA、p-ERK1/2、p-NF-κB蛋白的水平明显升高(P<0.05)。与Model组相比,ICSⅡ-M、ICSⅡ-H剂量组肺动脉中膜肥厚显著改善;PCNA、p-ERK1/2、p-NF-κB蛋白的水平明显降低(P<0.05)。结论 ICSⅡ具有抗MCT所致大鼠肺动脉重构的作用,其机制可能与抑制ERK1/2-NF-κB信号通路有关。

Objective To investigate the effects of IcarisideⅡ（ICSⅡ） on pulmonary artery remodeling induced by monocrotaline（MCT） in rats and to explore its effect on ERK1/2-NF-κB signaling pathway. Methods SD rats were randomly divided into control group,ICS Ⅱ alone group（Control ＋ ICS II-H,16 mg/kg）,model group,low-dose（ICS II-L,4 mg/kg）,middle-dose（ICS II-M,8 mg/kg） and high-dose（ICS II-H,16 mg/kg） of ICS II treatment group,6 in each group. The rats in the model group and ICS II-L,ICS II-M and ICS II-H groups were injected subcutaneously with MCT to establish the model of pulmonary artery remodeling.On the first day after MCT injection,ICS II was given once a day by intragastric administration for 28 days according to groups. After 28 days of administration,the morphological changes of pulmonary artery were observed by HE stain. The protein levels of PCNA,p-ERK1/2 and p-NF-κB were detected by immunohistochemistry. Results Compared with control group,the medial hypertrophy of pulmonary arterioles were significantly observed,and the expressions of PCNA,p-ERK1/2 and p-NF-κB proteins were increased（P〈0. 05） in model group. Compared with the model group,the medial hypertrophy of pulmonary arterioles were improved,and the protein levels of PCNA,p-ERK1/2 and p-NF-κB were decreased（P〈0. 05） in ICSII-M and ICSII-H groups. Conclusion ICS II can resist pulmonary artery remodeling in MCT-induced rats,which may be related to inhibit the activation of ERK1/2-NF-κB signaling pathway.