银杏叶提取物对慢性阻塞性肺疾病大鼠肺组织MMP-1及MMP-9表达的影响

Effects of Ginkgo Biloba Extract on Expressions of MMP-1 and MMP-9 in Lung Tissue in Rat Model of Chronic Obstructive Pulmonary Disease

目的:研究银杏叶提取物(GBE)对慢性阻塞性肺疾病(COPD)大鼠肺组织基质金属蛋白酶-1(MMP-1)及基质金属蛋白酶-9(MMP-9)表达的影响。方法:将清洁级同龄雄性Wistar大鼠36只称重后,随机分为正常对照组(A组)、COPD对照组(B组)、GBE早期干预组(C组)、GBE后期干预组(D组)、红霉素早期干预组(E组)、红霉素后期干预组(F),每组6只。B、C、D、E和F五组采用烟雾吸入、脂多糖气管内注入等因素对大鼠进行COPD造模,C和D组分别在1~14 d和29~42 d腹腔内注射GBE[0.40 m L/(kg·d)],E和F组分别在1~14 d和29~42 d腹腔内注射红霉素(10 mg/kg^2),43 d后采集各组大鼠肺组织,采用免疫组织化学分析法检测各组大鼠肺组织MMP-1和MMP-9的表达及含量。结果:B、C、D、E和F组大鼠肺组织MMP-1及MMP-9阳性细胞表达率均高于A组,B组的MMP-9阳性细胞表达率高于其他组。结论:GBE可通过降低大鼠肺组织中MMP-9的表达,从而预防和减少COPD大鼠肺组织重塑及纤维化。在通过MMPs在COPD大鼠肺组织中的表达来判断肺组织重塑及肺纤维化上,MMP-9与MMP-1相比较具有更高的敏感性。红霉素在降低MMP-1及MMP-9在COPD大鼠肺组织中的表达作用不明显,因此红霉素抗肺组织纤维化的作用机制还有待进一步研究。

Objective ： To study the effects of ginkgo biloba extract on the expression of MMP - 9 and TIMP - 1 in the lung tis- sue in rat model of chronic obstructive pulmonary disease（COPD）. Methods ：36 wistar rats were randomly divided into group A, B, C, D,E and F. There were six rats in each groups. The rat model of COPD was established by being exposure to cigarette smoke, intratracheally injection of lipopolysaccharide and the cold air stimulation composite factors in groups B, C, D, E and F five groups. Group C and D were given intraperitoneally injection with GBE [0.40 mL/（ kg · d） ] from day 1 to day 14 and day 29 to day 42. Group E and F were given intraperitoneally injection with erythromycin （10 mg/kg^2 ）from day 1 to day 14 and day 29 to day 42. Collect the lung tissue of each groups after forty- three days later,expressions and contents of MMP- 9 and TIMP- 1 were determined by immunohistochemical analysis. Results：Group B, C, D, E and F＇s positive cells expression rate of MMP - 1 and MMP - 9 were higher than those of A group. The positive cells expression rate of MMP - 9 on B group was higher than that of other groups. Conclusion ： GBE can control the lung tissue remodeling and pulmonary fibrosis in rats of chronic obstructive pulmo- nary disease by reducing the MMP - 9 expression in COPD rats lung tissue. Through the MMPs expressions in COPD rats lung tis- sue to determine the lung tissue remodeling and pulmonary fibrosis, MMP -9 has a higher sensitivity compared with MMP - 1. The effect of erythromycin in reducing the MMP - 1 and MMP - 9 expressions in lung tissue in COPD rats is not obvious, so the mech- anism of ervthromvcin resistance to pulmonary fibrosis need further research.