[Inhibitory effect of melatonin on the expression of nuclear factor-kappaB during acute lung injury in rats].

OBJECTIVE: To investigate the protective effect of melatonin (MT) on lung tissue during acute lung injury (ALI) in rats and its possible mechanism. METHODS: Ninety-six Sprague-Dawley (SD) rats were randomly divided into four groups: control group, lipopolysaccharide (LPS) group, dexamethasone (DEX) and MT treatment group, with 24 rats in each group. Rat model of ALI was established by instilling LPS intratracheally, and DEX and MT were injected intraperitoneally. All rats in each group were sacrificed at 3, 6 and 12 hours after intratracheal instillation of LPS, and lung tissue samples were harvested. Myeloperoxidase (MPO) activity, superoxide dismutase (SOD) activity and malondialdehyde (MDA) contents in lung tissue samples were detected in each group. In addition, the expression of nuclear factor-kappaB (NF-kappaB) was assessed with immunohistochemistry staining in lung tissues. RESULTS: Compared with control group, SOD activity in LPS group decreased at different time points significantly (P<0.05 or P<0.01), but MPO activity, MDA content and the expression of NF-kappaB increased obviously (P<0.05 or P<0.01); the administration of MT and DEX could mitigate above values significantly (P<0.05 or P<0.01). The changes in above each indexes were most obvious at 6 hours, either reaching the peak or the trough, respectively. CONCLUSION: MT possesses protective effect on lung tissues during ALI through scavenging free radicals and inhibiting the activation of NF-kappaB.

[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.

Evaluation of the early response and mechanism of treatment of Parkinson's disease with L-dopa using 18F-fallypride micro-positron emission tomography scanning.

The aim of the present study was to investigate the use of 18F-fallypride micro-positron emission tomography (micro-PET) imaging in the evaluation of the early therapeutic efficacy of L-dopa in the treatment of Parkinson's disease (PD) and the underlying mechanism. 18F-fallypride was synthesized and its specific binding with dopamine (DA) receptors in normal mouse brain was studied. Following the establishment of a mouse model of PD, the animals were divided into normal control, PD model and L-dopa treatment groups. General behavior, swimming test, locomotor activity counts, transmission electron microscopy, immunohistochemical analysis, high performance liquid chromatography-electrochemical detection and 18F-fallypride micro-PET imaging were used to study intergroup differences and the correlation between the changes of striatal uptake of 18F-fallypride and the therapeutic efficacy. The general behavioral features of PD model mice were similar to the clinical symptoms of PD patients and were alleviated after treatment. The swimming time, locomotor activity and frequency of standing posture of PD model mice were lower than those of the control mice, but had no difference from those of the control mice after L-dopa treatment. The number of tyrosine hydroxylase-positive neurons and the striatal contents of glutathione peroxidase, superoxide dismutase, DA and its metabolites 3,5-dihydroxyphenylacetic acid and homovanillic acid in the PD group were lower than those in the control group, but were significantly improved following the treatment; the significant reduction in DOPAC/DA and HVA/DA ratios post treatment suggested that the rate of DA metabolism decreased significantly. The striatal malondialdehyde content in the PD group increased compared with that in the control group, but was reduced after L-dopa treatment. Micro-PET imaging indicated that the uptake of 18F-fallypride in the mouse striatum of the PD group was lower than that of the control group and was significantly increased after the treatment. The mechanism of treatment of PD with L-dopa in mice may involve increasing the number of TH-positive cells and DA receptor levels, as well as reducing the rate of DA metabolism; such changes can be noninvasively observed in vitro by 18F-fallypride imaging.

[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.