The Effects Of Compositive Salvia Miltiorrhizel On Inflammatory Mediators In Early Phase Of Acute Lung Injury

Background: Acute lung injury(ALI) is characterized by an intense inflammatory reaction with neutrophil infiltration. Therefore, the inflammatory process is the major target of novel therapies in ALI. Compositive Salvia Miltiorrhizel parenteral solution is an anti-thrombosis agent. It has also been shown to have anti-inflammatory effect and to protect animals from endotoxin induced septic shock. However, it is unknown that whether Compositive Salvia Miltiorrhizel is effective on inflammatory reactions in early phase of acute lung injury. Objective: Our goals is to investigate the effect of compositive salvia miltiorrhizel parenteral solution on the inflammatory reactions in "two-hit" acute lung injury animal model. Methods: Twenty-four health rabbits were randomly divided into two groups (n=24): (1) The "Two-hit" acute lung injury control group: Hemorrhagic shock was initiated by blood withdrawal from femoral artery. Animals were resuscitated by transfusion of the shed blood and/or Ringer's lactate after a hypotensive period of 60 minutes. LPS(10μg/Kg) were then administrated by intravenous injection at one hour after resuscitation , and the animals were observed for 4 hours. (2) The compositive salvia miltiorrhizel parenteral solution treatment group: The animals were given compositive salvia miltorrhizel parenteral solution (5g/kg) and LPS by intravenous injection and the other procedures were same as (1). The changes of MAP, RR, HR were monitoring continuous. Blood were sampled for the measurement of TNFα, IL-8, TXB2, 6-keto-PGF1α, CRP concentration and arterial blood gas at baseline, and during hemorrhagic shock, resuscitation, as well as 2 and 4 hours after LPS administration. The animals were sacrificed by bleeding at the end of experiment. The lung, heart, liver and renal were removed for pathology studies. Result: In ALI control group, the PaO2 reduced significantly from 88.28±12.6 to 62.21±9.34mmHg(p＜0.05). Pathological studies showed lungs injuries of various degrees. Compared with baseline levels,the serum concentrations of TNFα, IL-8, TXB2, 6-keto-PGF1αincreased significantly at 2 and 4 hours after LPS administration(49.91±15.25ng/l, 53.68±9.01ng/l vs 17.65±5.88; 2.36±0.26ng/l, 2.62±0.14ng/l vs 1.38±0.19；524.24±267.59pg/l, 1583.80±522.42pg/l vs 230.97±65.28; 1158.78±272.39pg/l, 1198.37±412.19 vs 282.71±119.85；p＜0.05). The serum CRP concentration only increased significantly at the stage of shock(14.0±1.8mg/l vs 11.4±1.4mg/l). Compared with control group, intravenous injection of compositive salvia miltiorrhizel (5g/Kg) increased the PaO2(88.01±8.60mmHg), decreased the serum concentrations of TNFα(18.03±6.04ng/l), IL-8(1.33±0.16ng/l), TXB2(484.22±352.96pg/l) significantly at 4 hours after LPS administration, and also reduced lung injury. In addition, compositive salvia miltiorrhizel seemed to increase 6-keto-PGF1α(1566.86±621.28pg/l) and CRP (15.7±1.9mg/l) level at 4 hours after LPS administration. Conclusion: We have used "Two-hit" approaches including hemorrhagic shock and intravenous administration of low dose LPS to produce acute lung injury models in rabbits. We have found that compositive salvia miltiorrhizel parenteral solution significantly increased the PaO2, decreased serum concentrations of inflammatory mediators or metabolites TNFα, IL-8, TXB2, and 6-keto-PGF1α and reduced lung injuries in rabbit models of ALI. Our results suggest that compositive salvia miltiorrhizel parenteral solution may have pretective effect on LPS-induced acute lung injury by modulating the formation of proinflammatory meditors.