| Background:Danshen, a traditional medical ingredient herbal drug derived from dried roots of Salvia miltiorrhiza Bunge, has been widely used for the treatment of various cardiovascular diseases. With many hydrophilic constituents identified, danshen has been shown to possess various biological properties, such as the improvement of microcirculation, dilation of the coronary arteries, anti-oxidation, anti-inflammatory, anti-myocardial ischemia and anti-apoptosis. tanshinone Tan , some lipophilic components in saliva mitiorrhizabge, contains o-quinone and para benzoquinone and is known as tanshinone Tan compounds. Among these constituents, tanshinoneⅡA, the most abundant and representative lipophilic diterpenoid quinine, shows much more bioactivity. Previous studies revealed the inhibition effect of tanshinoneⅡA or other bioactive constituents of danshen on cancer, inflammation, liver fibrosis from different species of animals. As priviously reported, TIIA and other bioactive constituents of danshen could exert a protection of lung injury induced LPS from difference species of animals, through inhibiting lung tissue inflammation via the depressing phospho-NF-κB, the PLA2 activity and the NO synthesis;decreasing cellular oxidation, cells injury and improving the permeability. Whereas, the effect of TIIA on lung injury induced by seawater is unclear.In drowning victims, acute respiratory failure and hypoxia are very common. The mechanism was invovled with lung respiratory failure induced by severe hypoxia,the Ps and BBMVEC damage, and the chang of AQP and ionic channel due to seawater. The the infiltration of inflammatory cells released the excessive MPO and oxygen free radical. There are no effective clinical treatments at present. As previously reported, dexamethasone could treat and prevent the lung injury induced by seawater through inhibiting the inflammation, and TIIA also could protect the LPS–induced lung injury in the same way. But what the effect of TIIA on the lung injury induced by seawater is still unknown.In the present study, therefore, we investigated whether the inflammation contributed to the mechanism of seawater aspiration-induced lung injury. Moreover, we investigated the effects and underlying mechanisms of STS on seawater aspiration-induced lung injury in rats.Object: 1. To prepared the seawater aspiration model.2. To explored protection effect of TIIA on the seawater aspiration-induced lung injury.3. To discovered the protection mechanism of TIIA in the the seawater aspiration-induced lung injury.Method:1. The rats were anesthetized was aspirated seawater (4ml/kg) through endotracheal inserted in the trachea.2. 24 rats were were divided into normal group, seawater group, seawater+TIIA group and TIIA group. In the seawater group rats were subjected to seawater aspiration. In the seawater+TIIA group rats received TIIA( 25 mg/kg )intraperitoneally at 30min after seawater aspiration. In the TIIA group rats received TIIA(25 mg/kg)intraperitoneally. The PO2, histological study, lung wet /dry weight ratio and MPO assay were measured, MIF in lung tissue was tested by western-blot assay.3.1) NR8383 cells were divided into into control group, seawater group, seawater+TIIA group, seawater+ISO-1group and TIIA group In the seawater group cells were incubated with 25% seawater for 4h. In ISO-1 treatment group cells were pretreated with MIF inhibitor ISO-1(50uM) for 30min before seawater treatment. In seawater+TIIA treatment group cells were pretreated with TIIA(25ug/ml) for 30min before seawater treatment. In the TIIA group cells pretreated TIIA (25 mg/kg) intraperitoneally. Supernatant was collected to test MIF, IL-6 and TNF-αexpression by ELISA. Then cell protein was extracted to determined the level of phospho-NF-KB in wester-blot.2) Cells were divided into control group, rMIF group, rMIF+TIIA group. Cells were incubated with rMIF (25ng/ml) for 4h. TIIA (25ug/ml) was pretreated 30 min before rMIF administration. IL-6 and TNF-αin supernatants were determined by ELISA.Results:1. The seawater aspiration model was reproduced well.2. seawater aspiration caused a markedly decrease in the PaO2 , acute alveolar damage and in?ammation and pulmonary edema in rats. Western blot results showed that seawater treatment caused an obvious increase of MIF, which was reduced by TIIA.3. 1) MIF expression was elevated as well as activated phospho-NF-κB and induced IL-6 and TNF-αafter incubated with seawater. Pretreated with ISO-1, phospho-NF-KB as well as TNF-αand IL-6 levels were reduced following seawater treatment. Administrated with TIIA ,consistance with ISO-I effect, MIF expression as well as subsequent phospho-NF-KB and induced TNF-αand IL-6 levels were also attenuated following seawater treatment.2) Administration of rMIF increased the synthesis of IL-6 and TNF-α, and treatment with TIIA (25ug/ml) almost abolished the effect of rMIF on cytokines.Conclusion:Our study demonstrated that MIF played an important role in the seawater aspiration induced lung injury. TIIA exerted a protective effect on the lung injury following seawater aspiration through downregulation of MIF via inhibition NF-κB as well as inflammatory mediators. These observations also suggested that application of TIIA may be an effective treatment for seawater drowning. |
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