Study On The Protective Mechanisms Of Aprotinin On ALI Induced By Thrombin In Rats

Objective: Thrombin, a serine protease with multiple functions, is involved in many intercellular effects, especially the inflammation processes. It has been testified that the effects of thrombin are mediated by a family of protease-activated receptors (PARs). PAR1, 3 and 4 are activated via cleavage by thrombin. It's reported that thrombin generation is an important role in the mechanisms of brain edema and brain injures in some studies. It has been well documented that cardiopulmonary bypass (CPB) increased the concentration of the thrombin due to exposure of blood to the artificial surface of the bypass circuit and heparin eutralization.It's still needed to be confirmed that if the thrombin could induced the lung edema and lung injure post CPB. Aprotinin, a naturally occurring serine protease inhibitor derived from bovine lung, has been found be widespread used during cardiopulmonary bypass and involved in surgical procedures as a consequence to decrease blood loss and transfusion requirements. Many clinical and laboratory researches had revealed that aprotinin can prevent lung injury induced by many factors, and aprotinin can inhibit the proteolytic cleavage of the protease-activated receptor 1 (PAR1) by thrombin in vitro and in vivo. However, the mechanisms on the protection of aprotinin have not been clear. In this study, we are about to rebuild a rat acute lung injury model induced by thrombin to invested the effects of promoting inflammation by thrombin, and the inhibition effects of aprotinin on inflammatic injure induced by thrombin activation were evaluated to observe the protective effect of aprotinin on rat lung in vivo, and to explore its possible mechanism.Materials and Methods:1. Establishment of thrombin induced ALI in rats Seventy-two healthy female SD rats weighting 200~230g were randomly divided into 3 groups: saline control (2 ml/kg, C), low-dose thrombin group (50 U/kg, T1) and high-dose thrombin group (100 U/kg, T2), 24 per group. After aneasthetized with intraperitoneal pentobarbital (60 mg/kg), normal saline or thrombin was intravenously administered in rats,...