The Inhibition Effect Of The Mucosolvan With Various Dose In Lipopolysaccharide-induced Acute Lung Injury Of Rats

Objective: Acute lung injury (ALI)/acute respiratorydistress syndrome (ARDS) is acute progressive respiratoryfailure which is induced by various kinds of internal or externallung factor except cardiogenic factor. The changes of ALI andARDS in the pathophysiology have same character, and ARDSis the aggravating ALI. In many years, the mortality of ARDShasn't reduced obviously. The ventilation strategies forprevention are still the capital measure to treat ALI/ARDS, butdrug treatment has not obviously progression. To reduce themortality of ARDS by the innovation of the ventilationstrategies isn't a basic therapeutics. Therefore the focus ofpresent study is to explore effective drug treatment method. Thisstudy aimed to observe the inhibition effect of the mucosolvanwith large dose in lipopolysaccharide-induced acute lung injuryof rats, and to observe the therapeutic efficacy of themucosolvan with different dose in acute lung injury of rats.Methods: sixty-four male Sprague Dawley ( SD )rats(provided by Center of Experiment Animal of HebeiMedical University) were randomly divided into four groups:normal control group (group H), ALI model group (group L),mucosolvan treatment group 1 (group M1), mucosolvantreatment group 2 (group M2). There were 16 rats in each group.Each group was divided into two sections, section a and b. 8 ratswere in each section. ALI was induced in rats of group L, M1and M2 by injecting lipopolysaccharide into caudal vein, whilerats of group H were injected saline into caudal vein. Meanwhile,the rats in group H and L received saline, and the rats in groupM1 and M2 mucosolvan (15mg/Kg and 30 mg/Kg) was injectedinto another caudal vein. The rats were sacrificed after 4 hours.The rats in section a were sampled arterial blood from carotidartery to detect blood gas analysis; and detected the level ofTNF-a in bronchoalveolar lavage fluid (BALF). The cell inbronchoalveolar lavage fluid was counted and classified also.The level of TNF-αand IL-10 were detected in blood serum,which was sampled from carotid artery of rats in section b. Theleft lungs of section b rats were excised for HE staining and inright lung tissue the contents of SOD and MDA were detected.Results:1.Pathology of lung tissueGross: The lungs of group H rats were stepless light pink,their surface were smooth,full of elasticity, their sections werestepless and no hemorrhagic spots. The lungs of group L weretumescence and hyperemia. Lots of hemorrhagic spots were ontheir surfaces and their sections were rarefaction, fragile andexudation. The lungs of group M1 and M2 were almost identicalon the whole. Their damage took a favorable turn.HE staining on the lung tissue: Through observing HEstaining on the lung tissue, we can find that the constitution ofalveolar of group H was normal, clear, and there weren'tpolymorphonuclear leukocyte and monocyte infiltration inalveolar space and interstitial. In group L, the constitution ofalveolar was destructed, a great deal of polymorphonuclearleukocyte and monocyte gathered in widening interstitial. Thedegree of alveolitis of the group M1 and M2 decreased comparedwith group L, but there were still some polymorphonuclearleukocyte and monocyte in interstitial.2. the results of cell count and classification in BALFThe results of cell count: The cell sum in BALF of group L,M1 and M2 were all larger than which of group H(P<0.01).That of group M1 and M2 were less than group L(P<0.01).Compared with group M1 and M2, the cell sum correlated withthe dose of mucosolvan. That of group M1 was larger than groupM2(P<0.01).the results of cell classification:macrophage: the macrophage percentage of group L, M1and M2 were all lower than group H(P<0.01). There wassignificant difference between group M1 and M2. The result ofgroup M1 was lower than that of group M2(P<0.05)and theresult of two group were all higher than that of group L(P<0.05).neutrophil: the neutrophil percentage of group L, M1 andM2 were all higher than group H(P<0.01),and the results ofgroup M1 and M2 were all lower than that of group L(P<0.05).The percentage of group M1 was higher than that of group M2(P<0.01).Lymphocyte: the lymphocyte percentage of all group weresimilar and there was no significant difference between any twogroups(P>0.05).3.the numeric value of blood gas analysisThe results of PH, PaO2 and PaO2/FiO2 of group L, M1 andM₂ were lower than that of group H(P<0.05). The result ofgroup L s was lowest. Group M1 and M2 were similar. There wasno significant difference(P>0.05). There were significantdifferences among group H, group L, group M1 (or M2)(P<0.05).4. SOD and MDAlevel in lung tissue homogenateThe SOD level in lung tissue homogenate in group Hhighest than other three group. The level of group L was lowest,and that of Group M1 was lower than Group M2.All of these wassignificant difference (P<0.05).The MDA level in lung tissue homogenate in group L, M1and M2 increased compared with group H. The level in group Lwas highest, and that of Group M1 was higher than that of GroupM2. All of these was significant difference(P<0.01).5. TNF-αconcentration in blood serum and BALFThe TNF-αconcentration in blood serum and BALF ofgroup L was highest, that of group H was lowest, and that ofgroup M₁ was higher than group M2. There were significant...