system
Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Animals, Anti-Bacterial Agents, Cell Culture Techniques, Disease Models, Animal, Doxycycline, Male, Matrix Metalloproteinase 9, Neutrophil Infiltration, Neutrophils, Pancreatitis, Rats, Rats, Inbred Lew, Respiratory Distress Syndrome, Adult.
user
Does inhibition of matrix metalloproteinase-9 with doxycycline reduce pancreatitis-associated lung injury? Context: Severe lung injury, responsible for up to 15% of mortality in acute necrotizing pancreatitis patients, is promoted by neutrophil (PMN) migration into the lung. We have previously demonstrated that pulmonary injury in acute pancreatitis is mediated by PMN-derived matrix metalloproteinase-9 (MMP-9). This study was conducted to evaluate the ability of the broad-spectrum MMP inhibitor doxycycline to prevent secondary pulmonary injury in acute pancreatitis. Eighteen rats were randomized into three groups: severe pancreatitis (SAP), severe pancreatitis + doxycycline (SAP+Dox) (30 mg/kg body mass) or control. Acute pancreatitis was induced by intraductal glycodesoxycholic acid and i.v. stimulation with cerulein. Lung sections were histologically graded for edema, microthrombi, atelectasis and hemorrhage. Active MMP-9 in lung tissue was measured with fluorescent assay (ELISA). Naphtol-AS-D-chloroacetate esterase staining was used to determine pulmonary PMN infiltration. The inhibitory effect of doxycycline on MMP-9-induced transmigration was confirmed in a Matrigel transmigration assay. Addition of doxycycline significantly reduced TNF-alpha-induced PMN transmigration across Matrigel membrane (12.6 +/- 2.6 vs. 20.1 +/- 3.9 PMNs; p < 0.05). SAP+Dox showed decreased concentration of active MMP-9 in lung tissue (37.89 +/- 1.75 vs. 46.29 +/- 3.68 ng/ml; p < 0.05) and as a result decreased pulmonary infiltration of PMNs (21.2 +/- 5.1 vs. 32.5 +/- 6.8; p < 0.05). Histological evaluation revealed decreased pulmonary edema (1.83 +/- 0.41 vs. 2.33 +/- 0.51, p < 0.05), atelectasis (1.67 +/- 0.52 vs. 2.33 +/- 0.52; p < 0.05) and pulmonary hemorrhage (2.5 +/- 0.55 vs. 1.83 +/- 0.41; p < 0.05) in SAP+Dox vs. SAP. These findings were paralleled by reduced pulmonary expression of active MMP-9.
assistant
Inhibition of MMP-9 activity with doxycycline reduced pancreatitis-associated lung injury and expression of MMP-9 in pulmonary tissue. Doxycycline reduced PMN migration in vitro and in vivo and therefore might represent a novel strategy for the prevention of secondary pulmonary complications in acute pancreatitis. Final Decision: yes