| Our previous studies indicated that the gastric mucosa of the rats with 6% ethanol exposure in 3rd to 14th days had the ability to resist subsequent injury of pure ethanol, which was related to the enhanced cell turnover of gastric mucosa. Various mechanisms contributed to this phenomenon, neither can explain it completely. It is well known that the ethanol can injury the gastric mucosa through multiple pathways, including direct assaulting, mediated by reactive oxygen species (ROS), and reducing gastric mucosal blood flow (GMBF). Whether this adaptive cytoprotection is related to the ethanol concentration is so far unknown. To clarify its mechanism, the following experiments were designed and performed.At first, the ability to resist the injury of pure ethanol and the cell turnover of gastric mucosa in rats treated with alcohol of 1%, 3%, 6%, 12%, and 24% concentration were examined, respectively. The adaptive cytoprotection was found only in 6% and 12% group. The enhanced cell turnover of gastric mucosa was also found in these two groups. These results indicated that this phenomenon could be induced by adequate chronic alcohol drinking, involving the role of enhanced gastric mucosal cell turnover. The gastric mucosal adaptive cytoprotection induced byethanol intake was related to both of drinking duration and ethanol concentration.Secondly, the resistance of gastric mucosa to 0.6N HC1 and HC1-ethanol were also investigated. The gastric mucosa treated with 6% ethanol for 3 days could not be able to against the injury of 0.6N HC1 and HC1-ethanol. It is well known that the cells renewing of gastric mucosa was 3 to 5 days. Our results supported the concept of the adaptive cytoprotection of gastric mucosa mediated by enhanced cell turnover. The results also indicated that stimulus with 6% ethanol did not increase the ability of cells to resist the injury of noxious agents (0.6N HC1, HCl-ethanol and so on). And the blood flow and microcirculation of gastric mucosa were not improved. We also investigated the duration of the ability against pure ethanol, and found it could last 3 days.Reactive oxygen species (ROS) were radical derivatives of molecular oxygen, including the superoxide radical (O2- ), hydrogen peroxide (H2O2), and the hydroxyl radical (OH). The gastric mucosal injury induced by ethanol was mainly mediated by ROS derived from ethanol stimulation. The nitric oxide (NO) was another important free radical. Overproduction of NO could damage gastric mucosa directly. NO also interacted with O2 to form the toxic species, peroxynitrite (ONOO-). On the other hand, it has been reported that NO could play a cytoprotection role in gastric mucosa. Our previous studies showed that the scavenging free radical ability of gastric mucosa had not been enhanced after treatment with 6% ethanol. In this case, we hypothesized that adaptive cytoprotection of chronic drinking rat gastric mucosa should be related to the production of NO. To address this issue, the expressions of neuronal nitrogen monoxide synthase (nNOS), endothelial nitrogen monoxide synthase (eNOS), and inducible nitrogen monoxide synthase (iNOS) were measured in gastric mucosa of rats treated with the ethanol in different concentration by semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. Inimmunohistochemical study, positive staining cells of all three NOSs were detected in both control and ethanol groups. The results of RT-PCR showed that iNOS mRNA was overexpressed in the rat gastric mucosa of the groups in which drinking 12% and 24% ethanol. In contrast, the rat gastric mucosa in other groups such as drinking 0%, 1%, 3%, and 6% ethanol, the mRNA of iNOS was not expressed. The mRNA of nNOS was expressed markedly in the control, 1%, 3%, and 24% ethanol groups, while not expressed in 6% and 12% ethanol groups. The mRNA of eNOS was expressed random in all groups. These results suggested that the adaptive cytoprotection induced by 6% or 12% ethanol may be associated with the downregulation of the act...
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