Chronic sojourn in hypoxic environment results in the structural remodeling of peripheral pulmonary arteries and pulmonary hypertension. We hypothesize that the pathogenesis of changes in pulmonary vascular structure is related to the increase of radical production induced by lung tissue hypoxia. Hypoxia primes alveolar macrophages to produce more hydrogen peroxide. Furthermore, the increased release of oxygen radicals by other hypoxic lung cells cannot be excluded. Several recent reports demonstrate the oxidant damage of lungs exposed to chronic hypoxia. The production of nitric oxide is high in animals with hypoxic pulmonary hypertension and the serum concentration of nitrotyrosine (radical product of nitric oxide and superoxide interaction) is also increased in chronically hypoxic rats. Antioxidants were shown to be effective in the prevention of hypoxia induced pulmonary hypertension. We suppose that the mechanism by which the radicals stimulate of the vascular remodeling is due to their effect on the metabolism of vascular wall matrix proteins. Non-enzymatic protein alterations and/or activation of collagenolytic matrix metalloproteinases may also participate. The presence of low-molecular weight cleavage products of matrix proteins stimulates the mesenchymal proliferation in the wall of distal pulmonary arteries. Thickened and less compliant peripheral pulmonary vasculature is then more resistant to the blood flow and the hypoxic pulmonary hypertension is developed., J. Herget, J. Wilhelm, J. Novotná, A. Eckhardt, R. Vytášek, L. Mrázková, M. Ošťádal., and Obsahuje bibliografii
In order to reduce tissue damage caused by ischemia-reperfusion injury, this study aims to investigate the protective effect and mechanism of α-lipoic acid on hepatic ischemia-reperfusion injury in rats. The bloodstream of rats was blocked in the left middle and left lateral liver lobes of the liver. Forty rats were randomly divided into two groups: treatment group and injury group. Rats were injected with either 25 mg/1 ml of α-lipoic acid (treatment group) or 1 ml of saline (injury group) into the caudal vein 15 min before hepatic ischemia-reperfusion. Rat serum alanine aminotransferase (GPT), glutathione (GSH) and superoxide dismutase (SOD) levels were examined at various time points (1, 3, 6 and 12 h) in both groups. Changes in nuclear factor kappa B P65 (NF-κB P65) expression in ischemia-reperfusion liver at various time points after reperfusion (1, 3, 6 and 12 h) were evaluated through immunohistochemistry assay. Changes in macrophage inflammatory protein-2 (MIP-2) mRNA and inducible nitric oxide synthase (iNOS) mRNA expression in ischemic reperfused rat livers were detected by RT-PCR. Serum GPT level was significantly higher in the injury group than in the treatment group (P<0.01). NF-κB P65, MIP-2 mRNA and iNOS mRNA expression in ischemic reperfused rat livers were significantly higher in the injury group than in the treatment group (P<0.01). Serum GSH and SOD levels were higher in the treatment group than in the injury group (P<0.01). Alpha-lipoic acid significantly reduced ischemia-reperfusion injury in rat livers. This may be associated to the direct scavenging of oxygen-free radicals, increased GSH production, and the activation of downstream media due to decreased NF-κB and GSH consumption.