人参皂苷Rh2通过VEGF/MMP-9信号通路抑制哮喘小鼠气道重塑的实验研究

Ginsenoside Rh2 Inhibits OVA-Induced Airway Remodeling by Modulating VEGF/MMP-9 Signaling Pathway in Asthmatic Mice

目的:探讨人参皂苷Rh2对支气管哮喘小鼠气道重塑及VEGF和MMP-9信号通路的影响。方法:60只清洁级雌性BABL/c小鼠,随机数字表法分为6组,每组10只,分别为A组为生理盐水对照组、B组为卵蛋白(OVA)哮喘组、C组为人参皂苷Rh2低剂量组、D组人参皂苷Rh2高剂量组、E组为SU5416治疗组、F组为地塞米松治疗组。在末次激发24h后所有小鼠取左肺组织行苏木精-伊红(HE)染色、Masson三色染色、PAS染色。取右肺组织分别用酶联免疫吸附法(ELISA),RT-PCR和Westernblot检测支气管肺泡灌洗液(BALF)中IL-4、IL-5、IL-13含量以及VEGF和MMP-9 mRNA、蛋白表达。结果:哮喘模型组小鼠与对照组相比较BALF中炎症细胞计数、IL-4、IL-5、IL-13水平增高;肺组织VEGF和MMP-9 mRNA、蛋白表达水平均显著高于对照组(P<0.01)。人参皂苷Rh2干预组小鼠与哮喘模型组相比较BALF中炎症细胞计数、IL-4、IL-5、IL-13水平,VEGF和MMP-9 mRNA、蛋白表达水平均显著降低,具有显著差异(P<0.01),但2个不同治疗组之间上述各指标间差异无统计学意义(P>0.05)。结论:人参皂苷Rh2可抑制哮喘小鼠气道重塑的发生,其机制有可能部分是通过抑制VEGF/MMP-9信号通路而实现的。

Objective：To investigate the effects of Ginsenoside Rh2（G Rh2） on airway remodeling and VEGF and MMP-9 signal transduction pathway in asthmatic mice.Methods：Sixty female BALB/c mice of clean grade were randomly divided into six groups with 10 mice in each group.Respectively,Group A：the saline control group;Group B：the egg protein（OVA） asthma group;Group C：Ginsenoside Rh2 low-dose group;Group D：Ginsenoside Rh2 high-dose group;Group E：SU5416 group;Group F：Dexamethasone（DXMS） group.All mice left lung tissues were stained by HE,PAS and Masson trichrome staining after the last excitation in 24 hours.Take the right lung tissues,respectively by enzyme linked immunosorbent assay（ELISA） detect the expression levels of IL-4,IL-5 and IL-13 in bronchoalveolar lavage fluid（BALF）.By RT-PCR detect the expression levels of VEGF and MMP-9 mRNA.By western blot detect the expression levels of VEGF and MMP-9 protein.Results：Compared with the control group,the inflammatory cell counts and the expression levels of IL-4,IL-5 and IL-13 in asthmatic model group were increased.The expression levels of VEGF and MMP-9 mRNA and protein from lung tissues were significantly higher than those in control group（P〈0.01）.Salidroside intervention groups compared with the asthma model group,the inflammatory cell counts,and the expression levels of IL-4,IL-5 and IL-13 in BALF,and the expression levels of VEGF and MMP-9 mRNA and protein were significantly decreased with significant differences（P〈0.01）.But,for indexes mentioned above,there were no statistical significances between the two different treatment groups.（P〉0.05）.Conclusion：Ginsenoside Rh2 might inhibit the development of airway remodeling in asthmatic mice and the mechanism might be partly achieved through theinhibition of VEGF/MMP-9 signal transduction pathway.