[Inhibitory effects of melatonin on the expression of phosphorylation p38 mitogen-activated protein kinase during acute lung injury in rats].

OBJECTIVE: To investigate the protective effect of melatonin (MT) on lung tissues during acute lung injury (ALI) in rats and its possible mechanism. METHODS: Seventy-two Sprague-Dawley (SD) rats were randomly divided into three groups: control group, lipopolysaccharide (LPS) group and MT treatment group. In LPS group and MT treatment group, 1 ml/kg of LPS (200 mug/200 mul) was administered through the airway. In MT group, 10 mg/kg of MT was injected intraperitoneally before and after administration of LPS, and 1 ml/kg of ethanol-normal saline was given in control rats. The rats were sacrificed at 3, 6, 10 hours after administration of LPS, and the lung tissue was obtained for determination of the contents of nitrogen monoxide (NO) and malondialdehyde (MDA), and activity of superoxide dismutase (SOD). In addition, the expression of phosphorylation p38 mitogen-activated protein kinase (p-p38 MAPK) in lung tissue was assayed with immunohistochemistry staining. RESULTS: Compared with control group, SOD activity (U/mg) decreased significantly in LPS group (3 hours: 73.78+/-3.62 vs. 112.69+/-3.26, 6 hours : 66.07+/-2.31 vs. 117.85+/-1.96, 10 hours: 55.13+/-5.26 vs. 118.27+/-2.16, all P<0.01), but NO (micromol/mg), MDA (nmol/mg) content and the expression of p-p38 MAPK [absorbance (A) value] increased obviously (NO: 8.19+/-0.48 vs. 2.32+/-0.20 at 3 hours, 11.71+/-0.27 vs. 2.08+/-0.15 at 6 hours, 16.53+/-0.60 vs. 2.76+/-0.21 at 10 hours; MDA: 11.43+/-0.68 vs. 2.86+/-0.21 at 3 hours, 19.63+/-1.29 vs. 2.85+/-0.19 at 6 hours, 26.63+/-2.00 vs. 2.84+/-0.28 at 10 hours; p-p38 MAPK: 0.340+/-0.020 vs. 0.238+/-0.019 at 3 hours, 0.410+/-0.016 vs. 0.218+/-0.024 at 6 hours, 0.578+/-0.066 vs. 0.238+/-0.036 at 10 hours, all P<0.01). The administration of MT mitigated above contents significantly [SOD (U/mg) was 86.02+/-2.81, 80.87+/-3.40, 94.46+/-5.03, NO (micromol/mg) was 3.80+/-0.28, 5.32+/-0.22, 7.24+/-0.52, MDA (nmol/mg) was 8.18+/-0.84, 7.84+/-0.78, 6.43+/-1.06, and p-p38 MAPK (A value) was 0.311+/-0.018, 0.312+/-0.019, 0.314+/-0.021 at 3, 6, 10 hours, respectively, P<0.05 or P<0.01]. CONCLUSION: MT possessed protective effect on lung tissues during ALI by its antioxidation effect and inhibition of over- expression of p-p38 MAPK.

[Protective effect of endogenous carbon monoxide on organs during septic shock in rat and its mechanisms].

OBJECTIVE: To study the protective effect of endogenous carbon monoxide (CO) on lung and liver during septic shock in rat and its mechanism. METHODS: Septic shock model was replicated by cecal ligation and puncture (CLP). Ninety-six rats were randomly divided into sham operation group, CLP group, CLP+ hemin (Hm) group and CLP+zinc protoporphyrin (ZnPP) group. The carboxyhemoglobin (COHb) levels of in-flowing pulmonary blood (IPB) and out-going pulmonary blood (OPB) were determined at 2, 4 and 6 hours after treatments. Malondialdehyde (MDA) contents and superoxide dismutase (SOD) activities in the lung, liver and blood were also determined. Pathological changes in lung and liver were examined with light microscope, and immunohistochemical technique was used for analysis of heme oxygenase-1 (HO-1) protein expression and distribution in lung and liver. RESULTS: Compared with sham operation group, the COHb level in OPB and IPB as well as MDA contents of lung, liver and blood significantly increased in CLP group, while the SOD activities significantly decreased at different time points (P<0.05 or P<0.01), and the pathological changes and expressions of HO-1 in two tissues were more marked. However, in CLP+Hm group the results of MDA, SOD activities and pathological changes were reversed. The content of COHb increased compared to those of CLP group. Immunohistochemical studies showed that there were more HO-1 positive deposits in CLP+Hm group than those in CLP group. CONCLUSION: Increase in endogenous CO may play a protective role in lung and liver during septic shock.

[Effects of melatonin on anti-oxidative function of lung injury induced by lipopolysaccharide in rats and ICAM-1 expression].

AIM: To investigate the protective effect of melatonin (MT) on lung tissues during acute lung injury (ALI) in rats and its possible mechanism. METHODS: All rats were randomly divided into four groups: control group, lipopolysaccharide (LPS) group, dexamethasone (DEX) and MT treatment group. Myeloperoxidase (MPO) activity, superoxide dismutase (SOD) activity and malonaldehyde (MDA) content of lung tissues were detected at 3, 6 and 12 h after intratracheal instillation in each group. In addition, the expression of intercellular adhesion molecule-1 (ICAM-1) were observed through immunohistochemistry staining in lung tissues. RESULTS: Compared with control group, SOD activity decreased significantly in LPS group (P < 0.01), but MPO activity,MDA content and the expression of ICAM-1 increased obviously (P < 0.01). The administration of MT and DEX mitigated above changes significantly (P < 0.05 or P < 0.01). CONCLUSION: MT possessed protective effect on lung tissues during ALI through scavenging free radicals and inhibiting the expression of ICAM-1 probably.

[Protective role of endogenous carbon monoxide to lung and kidney tissues during septic shock].

AIM: To study the protective role of endogenous carbon monoxide to lung and kidney tissues during septic shock and its mechanism. METHODS: A rat model of CLP was built by using the method of CLP. The malondialdehyde (MDA) content and the activity of superoxide dematase (SOD) in blood, lung and kidney were detected by immunohistochemical technique and light microscope. RESULTS: Pathological changes of lung and kidney in CLP + Hemin group were lighter than CLP group, inflammatory reaction and lipid peroxidation were also lighter. CONCLUSION: Endogenous CO can protect lung and kidney from the oxidative injury. It can suppress in flammation and the oxidative injury caused by activated inflammatory cells, it is probably an important mechanism of its protective effects.