平喘宁对哮喘大鼠肺组织Raf mRNA、ERK1 mRNA表达的影响

Effects of Pingchuanning Decoction on the expressions of Raf mRNA, ERK1 mRNA in lung tissues of asthma rats

目的:观察平喘宁对哮喘大鼠Raf mRNA、ERK1 mRNA表达及基质金属蛋白酶-9(MMP-9)、金属蛋白酶组织抑制物-1(TIMP-1)含量的影响,探讨其治疗哮喘的相关作用机制。方法:雄性Wistar大鼠70只,随机分为正常组、模型组、地塞米松组、桂龙咳喘宁组以及平喘宁高、中、低剂量组,每组10只。以卵蛋白致敏及寒冷刺激复制大鼠哮喘模型,造模21d后,正常组、模型组每天给予蒸馏水灌服,其它各组给予相应药物灌服,4周后解剖大鼠并取出肺组织。用SP免疫组化法观察TIMP-1、MMP-9含量,用RT-PCR法观察Raf mRNA、ERK1mRNA在平喘宁治疗哮喘前后的变化。结果:与正常组比较,模型组肺组织MMP-9、TIMP-1、Raf mRNA、ERK1mRNA显著性上调(P<0.01);与模型组比较,各治疗组以上指标均有不同程度的下调(P<0.05,P<0.01);平喘宁中、高剂量组和地塞米松组比较,无显著性差异。结论:平喘宁可通过下调MMP-9和TIMP-1的表达,并调节MMP-9/TIMP-1之间的平衡,显著降低哮喘大鼠肺组织ERK信号通路Raf mRNA、ERK1 mRNA的表达而治疗哮喘。

Objective： To observe the effects of Pingchuanning Decoction on the expressions of Raf mRNA, ERK1 mRNA and the contents of MMP-9, TIMP-1 of rats with asthma. Methods： Seventy male wistar rats were randomized into seven groups, ten in each. To copy the asthma model with ovalbumin sensitized and cold stimulation in rat for 7 days. Normal, model control groups were gived the same amount of distilled water every day gavage, the other groups were given relevant medicine. After four weeks, the rats were dissected and taken out the lung tissues. The contents of MMP-9, TIMP-1 in lung tissue were measured with immunohistochemical determination. Expressions of Raf mRNA and ERK1 mRNA in the lung tissue were detected by RT-PCR. Results： Compared with the normal group, the contents of MMP-9, TIMP-1, Raf mRNA, ERK1 mRNA in asthma model group lung tissue were significantly improved （P〈0.01）. Compared with model group, the above indicators of the treatment groups had different degrees of reduction （P〈0.05, P〈0.01）. Compared with dexamethasone group, the medium-dose and high- dose group had not significant differences. Conclusion： Pingchuanning Decoction has obvious effect of treating asthma and its mechanism is probably due to the reduction expression of Raf mRNA, ERK1 mRNA, MMP-9, TIMP-1.