ABSTRACT
Objective To verify whether iron can accelerate the process of liver fibrosis in rats. Methods The rats were divided into control group, high fat diet group, high iron group, high fat diet and high iron group, high fat diet and de?iron group, each with 24 rats. The rats were allowed to freely take normal diet and high fat diet, while the high iron rats, high?fat diet plus high iron rats received intramuscular injection of 50 mg/kg iron dextran every other day;high?fat di?et plus de?iron group rats received tail intravenous injection of 30 mg/kg deferoxamine one month before death, 3 times/week. 8 rats were selected at 4th, 5th, 6th month of intervention, to detect serum hyaluronic Acid (HA), collagen type IV ( COL?IV) , laminin ( LN) , procollagen III ( PC III) , and observe pathological changes in the liver with Masson staining. Results At 5th month of intervention, serum HA level of the high?fat diet plus high iron group was significantly higher than those of high fat diet group and control group. At 6th month of intervention, serum COL?IV and LN levels of the high?fat diet plus high iron group were significantly higher than those of the high fat diet group. At 6th month, serum PC III level was 1. 63 time of those of the high fat diet group. At the 6th month, liver tissue of high fat diet plus high iron group ap?peared collagen deposition revealed by Masson staining, which was not the case in other groups. Conclusions Iron can accelerate high fat?induced liver fibrosis.
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Aim To investigate the protective effects and mechanisms of a 5-lipoxygenase (5-LO) inhibitor zileuton on the acute lung injury (ALI) induced by focal cerebral ischemia-reperfusion injury (CIRI) in rats.Methods The right middle cerebral artery in rats were occluded by inserting a thread through internal carotid artery for 2 h,and then reperfused for 24 h.Zileuton(10,50 mg?kg-1) was orally administered 2h before ischemia and 0,5,10 h after reperfusion.Morphological changes of the lung tissue were observed by hematoxylin-eosin (HE)staining technique. Lung wet/dry weight ratios were detected to observe the water content of the lung. The mRNA of cysteinyl leukotrienes recepor1 (CysLTR1) was detected by RT-PCR. The content of Leukotriene B4 (LTB4) in serum was measured by enzyme linked immunosorbent assay (ELISA) technique. The expression of TNF-? protein was measured by immunohistochemical technique. The activities of MPO, T-AOC, and Na+,K+-ATPase from the lung tissue were measured by biochemical method.Results With the use of zileuton 10, 50 mg?kg-1,the pathological changes of the lung were alleviated. and the wet/dry weight in the lung tissue was reduced(P
ABSTRACT
AIM:To investigate the influential factors of the blood-brain barrier (BBB) permeability and to observe the effects of zileuton,a selective 5-lipoxygenase inhibitor (5-LO),on focal cerebral ischemia-reperfusion injury (CIRI).METHODS:The right middle cerebral artery of the rat was occluded by inserting a thread through internal carotid artery for 2 h,and then reperfused for 24 h. Zileuton (10,50 mg?kg-1,po) was orally administered 2 h before ischemia and at 0,5,10 h after reperfusion. The permeability of blood brain barrier (BBB) was detected by using Evans blue (EB) as a labelling compound. The degree of cerebral edema was estimated by AutoCAD image analysis software. The mRNA of cysteiny leukotrienes receptor1 (CysLTR1) was detected by RT-PCR. The content of LTB4 in serum was measured by enzyme linked immunosorbent assay (ELISA). The expressions of AQP4 and MMP-9 proteins were measured by immunohistochemical staining method. RESULTS:After middle cerebral artery occlussion 2 h/reperfusion 24 h,the permeability of BBB in the brain tissue of injured side and the brain edema degree were increased. The content of LTB4 in serum was elevated. The expression of CysLTR1 mRNA from the brain tissue of occluded side was enhanced. The expressions of MMP-9 and AQP4 proteins of the ischemia realm and ischemia penumbra (IP) of the infarct focus perimeter were increased. Both 10 and 50 mg?kg-1 doses of zileuton dramatically relieved the BBB permeability destruction and the degree of the brain edema,inhibited the expression of CysLTR1 mRNA in the brain tissue and also reduced the content of LTB4 in serum. The expressions of AQP4 and MMP-9 proteins in the brain tissue were also decreased.CONCLUSION:The permeability of BBB is destroyed after the focal CIRI. The mechanisms of protective effect of zileuton might be attributed to its effects by inhibiting the activation of 5-LO pathways on the brain tissue and circulatory blood,reducing the expressions of AQP4 and MMP-9 proteins of the ischemia and IP realm in the brain tissue.