Effects Of MARCKS-related Peptide And Diltiazem On Airway Mucus Hypersecretion

Objective The purpose of this study was to investigate the following aspects on the rat model of airway mucus hypersecretion induced by aerosol Acrolein inhalation: 1, To manifest the effects on airway mucus secretion via intratracheal instillation which included administrations of MARCKS-related peptide or Diltiazem respectively and both of them simultaneously; 2, To elucidate the probable mechanism in which MARCKS-related peptide and Diltiazem are very likely to play amazing roles in attenuating mucus secretion.Methods Rat models of airway mucus hypersecretion were established by aerosol inhalation of 3.0 PPM Acrolein for 6 hours per day for 12 days. The experimental groups were administered via intratracheal instillation of MARCKS-related peptide ( 10mg/Kg ) or Diltiazem ( 0.2mg/Kg ) respectively and both of them simultaneously while the control groups were implemented with saline. 30 minutes later, intraperitoneal injection of pilocarpine (150 mg/Kg) was administered in order to stimulate mucus secretion. Half an hour later, BALF and lung specimens were acquired for detection. Mucin in BALF was detected semiquantitatively by ELLA; ELISA was employed to detect Mucin5AC in BALF. Intracellular Mucin5AC was detected by immunohistochemical staining. The average optical density of positive staining of Mucin5AC was determined by image analysis technique and gray scale scanning.Results Compared with control group: 1, Intratracheal instillation of MARCKS-related peptide significantly attenuated both Mucin andMucin5AC in BALF (P<0.05 respectively); 2, Intratracheal instillation of Diltiazem, however, failed to significantly decrease Mucin or Mucin5AC in BALF (P>0.05 respectively).In the group of Simultaneous instillation of MARCKS-related peptide and Diltiazem, both Mucin and Mucin5AC were significantly attenuated , when compared respectively with the three groups administered with MARCKS-related peptide, Diltiazem or saline alone (P < 0.05 respectively).Compared with the control group, intracellular Mucin5AC , either in the group of MARCKS-related peptide or in the group of MARCKS-related peptide in combination with Diltiazem, significantly increased (P<0.05 respectively), while the group of Diltiazem did not significantly increase (P >0.05).Conclusions hi the rat model of airway mucus hypersecretion induced by aerosol Acrolein inhalation, intratracheal instillation of MARCKS-related peptide can attenuate mucus secretion ; Intratracheal instillation of Diltiazem is likely to co-operatively decrease mucus secretion when it is in combination with MARCKS-related peptide, although it fails to attenuate mucus secretion when administrated alone; meanwhile, Mucin5AC is retained in goblet cells due to attenuation of extracellular mucus secretion .