| Hemorrhagic shock(HS) is a common acute disease of surgery. Organ injury is a serious complication of HS, acute lung injury(ALI) usually occurs early in organ injury after HS, it can develop easily into acute respiratory distress syndrome (ARE)A), so much as multiple organ dysfunction syndrome (MODS), its mortality rate is 50-70 percent. At present, gut origin endotoxemia is deemed to be a major reason for ALI after HS. I kappa B kinase(IKK) -B plays a crucial role in the activatory process of nuclear factor -kappa B (NF- K B) which is an ubiquitous rapid response transcription factor, it can degrade inhabitory kappa B (1KB), expose the nuclear localization sequence (NLS), and make NF- K B translocate from the cytoplasm to the nucleus where it upregulates the transcription of inflammatory cytokines that lead to uncontrollable inflammatory reaction and induce ALI. Anisodamine is from anisodus tonguticus and has many biological effects, including protective effect of cells and anti-inflammatory action. This study was conducted to establish the experimental animal models of ALI by HS andThis Study Was Supported by Nature Science Fund of China. (No.30000165)endotoxin(ET), to evaluate the expression of IKK-βmRNA and activation of NF- кB p65 in lung tissues and the content of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6 in bronchoalveolar lavage fluid(BALF), and to discuss the role of IKK- NF- K B pathway in pathogenesis of ALI after HS; At the same time, by treatment with anisodamine we observed its protective effects on ALI and investigate its role in molecular mechanisms of anti-inflammatory action. We intended to approve that intervening IKK- NF-кB pathway was an effective approach to preventing the generation and development of ALI after HS, and to provide experimental basis for the prophylaxis and treatment of ALI after HS.METHOD: Fourty-five healthy adult rabbits were randomly divided into three groups: the normal control group (group C, n=15), HS and ET group (group M, n=15) and anisodamine treatment group (group T, n=15). The rabbits anesthetized by 3% pentobarbital sodium intravenous injection through auricular vein. The right femoral artery was exposed and cannulated for monitoring of mean arterial pressure (MAP), blood sampling, and resuscitation. HS was initiated by blood withdrawal till the MAP reached about 30mmHg within 15min and maintained this level for 60min, then animals were resuscitated by transfusion of the shed blood. At Ih after resuscitation, Lipopolysaccharide (LPS, Escherichia coli 655: 85, 10ug / kg) was administrated by intraperitoneal injection. In addition, anisodamine (3mg/kg) was given to the group T by intraperitoneal injection at the end of shock period. Animals in the group C underwent the same surgical procedures, but HS was not induced , anisodamine and LPS was replaced by saline at the same dose. Every group rabbits were killed at 2h, 6h and 24h after animal models werefinished. The content of TNF-α and IL-6 in BALF was measured by enzyme linked immune adsorbing analysis(ELISA); The expression, distribution and relative content of IKK-β mRNA and NF- кB p65 in lung tissues were determined by using In situ hybridization (ISH) and Immunohitochemistry (IHC) combined with in situ quantitative analysis; The pathological changes of lung tissues were examined with light microscope; In addition, the value of partial pressure of arterial oxygen (PaO2) was detected.RESULT:(1) After HS and ET stimulation, PaO2 went down significantly, reached the lowest point 7.21\1.18 kPa at 6h , and went up to 9.32\0.95 kPa at 24h, there was significant difference in comparison with group C (P<0.01, P<0.05). In group T, the descent range of PaO2 was minished, PaO2 reached the lowest point 9.25\0.90 kPa at 6h, but there was significant difference in comparison with group M (P<0.05); and resumed to the level of group C at 24h (P>0.05). (2)In group M, the inflammatory pathological changes appeared in lung tissues and reached the severe phase at 6h. In gro...
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