Effects of TCM Staged Sequential Therapy on Expressions of Matrix Metalloproteinase-9 and Its Inhibitor in Asthmatic Rats with Airway Remodeling / 世界科学技术-中医药现代化

ABSTRACT

This study was aimed to verify the effects of staged sequential therapy on expressions of matrix metalloproteinase-9 (MMP-9) and its inhibitor TIMP-1 within lung tissues in asthmatic rats with the airway remodeling, by applying a series of tests such as the immunohistochemistry, western blot and real-time fluorescent quantitative PCR. SD rats were randomly divided into 7 groups, which were the asthmatic group (Group X), the normal group (Group Z), the No. 1 sequential therapy group (Group A1), the No. 2 sequential therapy group (Group A2), the No. 3 sequential therapy group (Group A3), the montelukast group (Group M), and the budesonide group (Group B). The asthmatic model was established in each group except Group Z, by sensitization with both ovalbumin (OVA) and aluminium hydroxide via injection at the 1st, 8th and 15th day in a 22-day duration, followed by OVA aerosol inhalation every other day for 8 weeks for asthma activation. At the 8th day after the asthmatic model was established, Group A1 was orally given Ma-Xing Er-Chen Tang (MXECT) during acute phase while given normal saline (NS) during catabasis and stable phase; Group A2 was given MXECT during acute phase, and given modified Jin-Shui Liu-Jun Jian (JSLJJ) during catabasis as well as given NS during stable phase; Group A3 was given MXECT during acute phase, and given modified JSLJJ during catabasis as well as given Liu-Wei Di-Huang (LWDH) Powders during stable phase;Group M was given salbutamol via aerosol inhalation after stimulation, while orally given montelukast during catabasis and stable phase; Group B was given salbutamol via aerosol inhalation after stimulation, while given inhaled budesonide during catabasis and stable phase; Group X was given NS. After the 7-week intervention, the immunohistochemistry, western blot and real-time quantitative PCR were applied to analyze the location and quantitative expression of MMP-9 and TIMP-1, so as to find out the biological mechanism on expressions of MMP-9 and TIMP-1 in lung tissues of asthmatic rats from molecular levels to gene levels. The results of immunohistochemistry, western blot and real-time fluorescent quantitative PCR showed as follows. Compared with Group Z, the contents of MMP-9 and TIMP-1 increased significantly within lung tissues in Group X. Compared with Group X, the contents of MMP-9 and TIMP-1 decreased within lung tissues of asthmatic rats in each treatment group. It was concluded that the expression of MMP-9 and TIMP-1 elevated during asthma. TCM staged sequential therapy can regulate the ratio between MMP-9 and its inhibitor so as to block the airway remodeling, by decreasing the expression of MMP-9 and its inhibitor within lung tissues in asthmatic rats. This is one of the important action mechanisms.