[Effect of mastoparan-1 on lipopolysaccharide-induced acute hepatic injury in mice].

OBJECTIVE: To observe the effect of mastoparan-1 (MP-1) on lipopolysaccharide (LPS)-induced acute hepatic injury in mice and probe into its possible mechanism. METHODS: One hundred and four BALB/c mice were randomly divided into healthy control group (n = 8, without treatment, HC), LPS group (n = 48, with injection of LPS 5 mg/kg via tail vein), and MP-1 group (n = 48, with injection of LPS 5 mg/kg and MP-1 3 mg/kg via tail vein). Mice in LPS group and MP-1 group were sacrificed at 2nd, 6th, 12th, 24th, 48th and 72nd post injection hour (PIH), 8 mice at each time point in each group. Blood samples were collected for determination of plasma levels of LPS by kinetic turbidimetric limulus test, TNF-alpha and IL-6 by ELISA, serum levels of ALT and AST by automatic biochemistry analyzer respectively. Hepatic tissue samples were collected for determination of TLR4, TNF-alpha and IL-6 mRNA by real-time fluorescent quantitation reverse transcription polymerase chain reaction, along with the observation of pathological changes in hepatic tissue at each time point. Above-mentioned examinations were also performed in HC group. RESULTS: Compared with those of HC group, plasma levels of LPS and TNF-alpha in LPS group significantly increased at 2nd PIH (18,320.50 +/- 2782.50 EU/mL and 988 +/- 130 ng/L, respectively), then decreased gradually to 1.80 +/- 0.80 EU/mL and 150 +/- 44 ng/L at 72nd PIH, which was close to those of HC group. The values of IL-6, ALT and AST peaked at 12th PIH, which declined to the levels close to those of HC group at 72nd PIH. Meanwhile, the expressions of TLR4, TNF-alpha and IL-6 mRNA in liver were remarkably up-regulated after injection, and the pathological changes in hepatic tissue pronounced significantly at 12th, 24th and 48th PIH. Compared with those of LPS group, the levels of LPS, cytokines, ALT and AST decreased in MP-1 group in different degrees after injection (P < 0.05 or P < 0.01), genes expression (P < 0.05 or P < 0.01) and pathological changes was respectively suppressed and alleviated in hepatic tissue. CONCLUSIONS: MP-1 can alleviate LPS-induced acute hepatic injury in mice, which may be associated with its neutralization of LPS and attenuation of synthesis and release of inflammatory mediators.

[The protective effect of high density lipoprotein on the lung function of rats with severe burns].

OBJECTIVE: To explore the protective effect of high density lipoprotein on the lung function of rats with severe burns. METHODS: One hundred and thirty-five Wistar rats were employed in the study and were randomly divided into control (n = 15, without injury), burn (n = 60, with 30% TBSA full-thickness burn on the back) and experimental [(n = 60, with the injection of HDL (80 mg/kg) via the caudal vein immediately after burns)] groups. The rats in the latter two groups were resuscitated with intraperitoneal isotonic saline (50 ml/kg) 30 minutes after burns. The serum content of ICAM-1 and TNF-alpha as well as the blood content of PCO2 and PO2 of the rats in burn and experimental groups were determined at 12, 24, 48 and 72 post-burn hours (PBH) and in control group. The pathological changes in the lung tissue of the rats in all groups were observed under light microscope and electronic microscope at 48 PBH. RESULTS: PCO2 and the contents of ICAM-1 and TNF-alpha in burn group were significantly higher, but the PO2 was lower than those in control group at each time-point (P < 0.05 or P < 0.01). There were no obvious differences in the above indices between the experimental and control groups (P > 0.05), but the ICAM-1 and TNF-alpha levels in experimental group were markedly decreased than those in burn group at each time-point (P < 0.05 or P < 0.01). The ICAM-1 and TNF-alpha contents in burn group at 48 PBH were (3.42 +/- 0.25) microg/L and (4. 04 +/- 0.28) ng/L, respectively, which were markedly higher than those in experimental group [(2.24 +/- 0.14) microg/L, (3.35 +/- 0.22) ng/L, P < 0.05 or P < 0.01]. Dilation of capillaries, congestion and inflammatory infiltration in the pulmonary capillaries, and loosening of conjunction between pulmonary capillary vascular endothelial cells and endothelial swelling were observed in burn group at 48 PBH. Compared with the burn group, the injury was markedly alleviated in the experiment group, and the pulmonary capillary endothelial cells showed tighter junction. CONCLUSION: HDL exhibits a protective effect on the lung function of rats with severe burns via reducing the expression of ICAM-1 and TNF-alpha.

Theaflavin ameliorates cerebral ischemia-reperfusion injury in rats through its anti-inflammatory effect and modulation of STAT-1.

Theaflavin, a major constituent of black tea, possesses biological functions such as the antioxidative, antiviral, and anti-inflammatory ones. The purpose of this study was to verify whether theaflavin reduces focal cerebral ischemia injury in a rat model of middle cerebral artery occlusion (MCAO). Male Sprague-Dawley rats were anesthetized and subjected to 2 hours of MCAO followed 24 hours reperfusion. Theaflavin administration (5, 10, and 20 mg/kg, i.v.) ameliorated infarct and edema volume. Theaflavin inhibited leukocyte infiltration and expression of ICAM-1, COX-2, and iNOS in injured brain. Phosphorylation of STAT-1, a protein which mediates intracellular signaling to the nucleus, was enhanced 2-fold over that of sham group and was inhibited by theaflavin. Our study demonstrated that theaflavin significantly protected neurons from cerebral ischemia-reperfusion injury by limiting leukocyte infiltration and expression of ICAM-1, and suppressing upregulation of inflammatory-related prooxidative enzymes (iNOS and COX-2) in ischemic brain via, at least in part, reducing the phosphorylation of STAT-1.

Determination of amino acid neurotransmitters in cerebral cortex of rats administered with baicalin prior to cerebral ischemia by capillary electrophoresis-laser-induced fluorescence detection.

An efficient, sensitive and rapid analysis of the amino acid neurotransmitters in the cerebral cortex of rats was developed by capillary electrophoresis with laser-induced fluorescence detection and fluorescein isothiocyanate (FITC) derivatization. This method was used to investigate the pharmacological effect of baicalin during cerebral ischemia. Different parameters which influenced derivatization and separation were optimized. The separation of amino acids was carried out in an uncoated fused-silica capillary (57 cm x 75 microm I.D.) with a buffer of 15 mM borate at pH 9.2 and an applied voltage of 17.5 kV. The detection limits for six amino acids were in the range of 2.1 x 10(-11)-6.3 x 10(-10) M. The changes in the level of amino acid neurotransmitters in brain cortex of three experimental rat groups were studied by this capillary electrophoresis-laser-induced fluorescence detection method. The results show that cerebral ischemia can cause a significant elevation in the concentrations of Glu, Asp, GABA, and Gly in cerebral cortex. Baicalin administration can attenuate the elevations of Glu and Asp induced by cerebral ischemia. This research demonstrates that baicalin may act as a neuroprotectant during cerebral ischemia.