Objective To investigate the effects of ambroxol hydrochloride on surface structure of trachea mucosa in rats injured by intratracheally instilled amikacin. Methods Thirty Wistar rats injured by intratracheally instilled amikacin ( 0. 252 mL/kg) were randomly divided into a control group ( n =15) and an ambroxol group ( n= 15) . The rats in the ambroxol group were intraperitoneally injected with ambroxol hydrochloride ( 70 mg/kg) 5 minutes after amikacin administration. They were all equally divided into five subgroups and sacrificed at 2, 4, 8, 28, 48 hours respectively. Then the samples of 1/3 lower segment of trachea were collected and observed under scanning electron microscope. Results In the control group, the mucous secretion and its stickness were increased. The cilia were found lodged, sticked together, aligned abnormally, abrupt partly, and recovered slowly, with the percentage of damaged area of 98. 2% , 98. 5% , 97. 5%, 92. 7% , 82. 1% at 2, 4, 8,24,48 h, respectively. The injuries of mucosa in the ambroxol group were much milder and recovered more rapidly than those in the control group, with the percentage of damaged area of 85. 7% , 81. 9% , 73. 0% , 61. 9% , 50. 2% at 2, 4, 8, 24, 48 h, respectively. Conclusions Intratracheal instillation of amikacin can cause cilia ultrastructure damage on tracheal mucosa. Ambroxol can promote the recovery process and alleviate airway inflammation.
Objective To investigate the effects of 1, 25-( OH) 2D3 on the expression of matrix metalloprotease-9 ( MMP-9) and nuclear factor κB ( NF-κB) activity in a murine model of chronic asthma. Methods BALB/ c mice were sensitized and challenged with ovalbumin to establish chronic asthmatic model. The animals were randomly divided into a control group, an asthma group and a VD group. Lung sections from the mice were stained by HE and Masson’s trichrome, respectively. Morphometric analysis of the stained sections was performed using computerized image analysis system. Nuclear translocation of NF-κB p65 was examined using Western blot. The level of IκBαwas detected with real-time quantitative PCR ( RTPCR) and Western blot. In addition, the expression of MMP-9 in both activity and mRNA level was detected by gelatin zymograph and RT-PCR, respectively. Results Prominent airway remodeling developed in the asthma group, including the inflammatory cell infiltration, subepithelial collagen deposition and increased airway smooth muscle mass. In contrast, 1, 25-( OH) 2D3 attenuated these established structural changes of the airways. Stimulation with OVA induced a 7. 87-fold increase in the MMP-9 activity compared with that in the control group, and 1, 25-( OH) 2D3 treatment only induced a 3. 46-fold increase in the MMP-9 activity compared with that in the control group ( P lt;0. 05) . The mRNA level of MMP-9 in the VD group ( 3.16 ± 0.09) was decreased compared with the asthma group ( 5.74 ±0.13) ( P lt;0.05) , but itwas still higher than that in the control group ( 0.57 ±0.08) ( P lt;0.05) . 1, 25-( OH) 2D3 reduced the nuclear translocation of NF-κB p65 while up-regulated the IκBα level in lung tissue of chronic asthma. Conclusions 1, 25- ( OH) 2D3 can inhibit the NF-κB activity and down-regulate the expression of MMP-9 in lung tissue of chronic asthma, thus alleviating the established chronic asthma-induced airway remodeling.