title: Captopril pretreatment protects the lung against severe acute pancreatitis induced injury via inhibiting angiotensin II production and suppressing Rho/ROCK pathway.
abstract: Acute pancreatitis (AP) usually causes acute lung injury, which is also known as acute pancreatitis associated lung injury (APALI). This study aimed to investigate whether captopril pretreatment was able to protect lung against APALI via inhibiting angiotensin II (Ang II) production and suppressing Rho/ROCK (Rho kinase) pathway in rats. Severe AP (SAP) was introduced to rats by bile-pancreatic duct retrograde injection of 5% sodium taurocholate. Rats were randomly divided into three groups. In the sham group, sham operation was performed; in the SAP group, SAP was introduced; in the pre-cpl + SAP group, rats were intragastrically injected with 5 mg/kg captopril 1 hour prior to SAP induction. Pathological examination of the lung and pancreas, evaluation of pulmonary vascular permeability by wet/dry ratio and Evans Blue staining, detection of serum amylase, Western blot assay for Ang II receptor type 1 (AT1), RhoA, ROCK (Rho kinase), and MLCK (myosin light chain kinase) were performed after the animals were sacrificed at 24 hours. After the surgery, characteristic findings of pancreatitis were observed, accompanied by lung injury. The serum amylase, Ang II, and lung expression of AT1, RhoA, ROCK, and MLCK increased dramatically in SAP rats. However, captopril pretreatment improved the histological changes, reduced the pathological score of the pancreas and lung, inhibited serum amylase and Ang II production, and decreased expression of AT1, RhoA, ROCK, and MLCK in the lung. These findings suggest that captopril pretreatment is able to protect the lung against APALI, which is, at least partially, related to the inhibition of Ang II production and the suppression of the Rho/ROCK pathway.
authors.affiliation: Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Qi-Hong
authors.initials: QH
authors.lastname: Yu
authors.affiliation: Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Jie-Fang
authors.initials: JF
authors.lastname: Guo
authors.affiliation: Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Xiao-Rong
authors.initials: XR
authors.lastname: Guo
authors.affiliation: Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Yi-Qi
authors.initials: YQ
authors.lastname: Du
authors.affiliation: Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai, China. Electronic address: Lzssmmu@163.com.
authors.forename: Zhao-Shen
authors.initials: ZS
authors.lastname: Li
mesh_terms: D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000804:Angiotensin II / Q000096:biosynthesis* / Q000097:blood; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology; D055370:Lung Injury / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010179:Pancreas / Q000187:drug effects / Q000473:pathology; D010195:Pancreatitis / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control*; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D054460:rho-Associated Kinases / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D002216:Captopril; D054460:rho-Associated Kinases; D000681:Amylases; D020742:rhoA GTP-Binding Protein
keywords: Acute pancreatitis associated lung injury; Ang II receptor type 1; Angiotensin II; Rho/ROCK pathway