Li Hou-Zhong, Gao Zhao-Yu, Huang Wei, Ren Gong-Ping, Xu Hong-Na, Zhang Xin, Fu Hui, Zhang Yu-Fei
Mudanjiang Medical University, Mudanjiang 157011, China.
Hongqi Hospital Affiliated Mudanjiang Medical University, Mudanjiang 157011, China.
Zhongguo Zhong Yao Za Zhi. 2017 Nov;42(21):4180-4186. doi: 10.19540/j.cnki.cjcmm.20170928.018.
To investigate the effects of Fritillariae Cirrhosae Bulbus on airway remodeling and matrix metalloproteinase-2(MMP-2), matrix metalloproteinase-9(MMP-9), tissue inhibitor-1 of metalloproteinase(TIMP-1) of a murine asthma model, and explore its mechanism in treatment of asthma. BALB/C murines were randomly divided into the normal group, model group, high dose group, low dose group, and positive control group. Except for the normal group, all the other groups received ovalbumin(OVA) to establish murine asthma model. After successful modeling, the murines in high dose group and low dose group were orally administered with Fritillariae Cirrhosae Bulbus powder at the dose of 18.0 mg•kg⁻¹ and 9.0 mg•kg⁻¹, respectively; the murines in positive control group were injected intraperitoneally with dexamethasone at the dose of 0.5 mg•kg⁻¹; while the murines in normal group and the model group were orally administered with the same volume of normal saline. All the drugs were given to murines per day for 28 d. The variations of airway responsiveness, variations of the total cell count and leukocyte differential count in bronchoalveolar lavage fluid(BALF), and the variations of thicknesses of bronchial wall and airway smooth muscle of each group were observed. The levels of MMP-2, MMP-9 and TIMP-1 were measured by ELISA; and the expression levels of MMP-2, MMP-9 and TIMP-1 mRNA were detected by RT-PCR. The results showed that as compared with the normal group, the airway responsiveness, the count of total cells, neutrophils, macrophage, lymphocytes, eosinophils in BALF, and the thicknesses of bronchial wall and airway smooth muscle were increased significantly in the model group(P<0.01); as compared with the model group, the above indicators were decreased significantly in the high dose group, low dose group and positive control group (P<0.05 or P<0.01). As compared with the normal group, the levels and expressions of MMP-2, MMP-9 and TIMP-1 mRNA were increased significantly in the model group(P<0.01); while as compared with the model group, these levels were decreased significantly in the high dose group, low dose group and positive control group(P<0.01). In conclusion, Fritillariae Cirrhosae Bulbus can improve airway remodeling in a murine asthma model, and its mechanisms may be related to down-regulating MMP-2, MMP-9 and TIMP-1 levels.
为探讨川贝母对小鼠哮喘模型气道重塑及基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-9(MMP-9)、金属蛋白酶组织抑制剂-1(TIMP-1)的影响,并探讨其治疗哮喘的机制。将BALB/C小鼠随机分为正常组、模型组、高剂量组、低剂量组和阳性对照组。除正常组外,其余各组均给予卵清蛋白(OVA)建立小鼠哮喘模型。造模成功后,高剂量组和低剂量组小鼠分别以18.0 mg•kg⁻¹和9.0 mg•kg⁻¹的剂量灌胃给予川贝母粉;阳性对照组小鼠腹腔注射地塞米松,剂量为0.5 mg•kg⁻¹;正常组和模型组小鼠灌胃给予等体积的生理盐水。所有药物均每日给予小鼠,持续28天。观察各组气道反应性变化、支气管肺泡灌洗液(BALF)中细胞总数及白细胞分类计数变化、支气管壁厚度及气道平滑肌厚度变化。采用酶联免疫吸附测定(ELISA)法检测MMP-2、MMP-9和TIMP-1水平;采用逆转录聚合酶链反应(RT-PCR)法检测MMP-2、MMP-9和TIMP-1 mRNA的表达水平。结果显示,与正常组相比,模型组气道反应性、BALF中细胞总数、中性粒细胞、巨噬细胞、淋巴细胞、嗜酸性粒细胞计数及支气管壁厚度和气道平滑肌厚度均显著增加(P<0.01);与模型组相比,高剂量组、低剂量组和阳性对照组上述指标均显著降低(P<0.05或P<0.01)。与正常组相比,模型组MMP-2、MMP-9和TIMP-1 mRNA水平及表达均显著升高(P<0.01);与模型组相比,高剂量组、低剂量组和阳性对照组这些水平均显著降低(P<0.01)。综上所述,川贝母可改善小鼠哮喘模型的气道重塑,其机制可能与下调MMP-2、MMP-9和TIMP-1水平有关。