| Objective:Gastroduodenal mucosal integrity is maintained by a delicate balance between invading-damaging and defending-repairing mechanisms. In the past20years, studies on invading-damaging factors have received an increasing attention and there have been epochal achievements in that field. However, in recent years with increasing age, an increase in the incidence of diseases like peptic ulcer and chronic erosive gastritis have been reported, which could be due to the age-related changes that take place in the gastric mucosal defense-repair mechanisms. Therefore, in this preliminary study we attempt to observe the gastric mucosa and pyloric glands in "relatively healthy" people of different age groups, and investigate any change that occurs with increasing age, in order to confirm the statement that gastric mucosal defense-repair mechanisms decline with aging.Method:1. FD patients aged20years or more without any gastroduodenal diseases and factors that could have affected the gastric mucosal integrity (for example:Hp infection, non-steroid anti-inflammatory drugs intake etc)were enrolled in the study. During gastroscopy if only superficial gastritis was found, then two samples of the gastric antral mucosa were taken. One specimen was used to carry out a routine pathological examination, and the other one was examined under electron microscope. Under light microscope the histologic features of the gastric antral mucosa were examined and the thickness of the lamina propria was measured. Then Ap to Al ratio calculated using i-SolutionTM sofeware. The ultrastructure of pyloric glands was examined under electron microscope, and then Am to Ac ratio was calculated using SigmaScan Pro5sofeware. With advancing age the changes associated with all these data were compared.2. Gastric surgery patients aged20years or more without Hp infection and no use of NSAIDs within2weeks were enrolled in the second part of this study. The indication for surgery included gastric stromal tumors, benign pyloric obstruction and early gastric cancer. Within10minutes of gastrectomy, under naked eye examination, two normal mucosal samples of1×1cm were taken from the greater curvature of the gastric antrum (with distance lesions≥5cm). One sample was used for routine pathological examination, and the other one was instantly frozen for molecular biological examination. The content of MDA in gastric antral mucosa was determined by TBA method, the content of NO by nitrate reductase, and the content of HSP70, PGI2、PGE2、PTEN、Survivin, CGRP、EGF、VEGF、COX-1、COX-2、 Caspase-3、Caspase-9、ZO-1by ELISA. Only specimens that were normal or had superficial inflammation after histopathological examination were included in the study.Results:After gastroscopy we recruited60subjects which we divided into a younger group (age20-59years, n=20) and an elderly group (age≥60years, n=40). We further divided the elderly group into3subgroups:60-69,70-79, and80-89years and they included15,13and12subjects respectively. After gastrectomy we recruited36subjects which we also divided into a younger group (age20-59years, n=14) and an elderly group (age≥60years, n=22). Here also the elderly group was divided into3subgroups as above and they included8,6and8subjects respectively.1. By qualitative analysis, no significant difference was found in the thickness of the lamina propria and the morphology of pyloric glands among all groups. However, interstitial hyperplasia was clearly seen in the lamina propria of the elderly group, who also had a sparse arrangement of the pyloric glands. By quantitative estimation, there was no significant difference in the thickness of lamina propria among all groups, however, there was a significant difference in the average ratio Ap:Al among all groups, P=0.005. When comparing the elderly and younger group, the thickness of the lamina propria in the elderly group was lower than that in younger group, but there was no significant statistical difference, P=0.578, and the average ratio Ap:Al of the elderly group was lower than that of the younger group, P=0.003.2. Under electron microscpy, no significant difference was found in the ultrastructure of the gastric pyloric gland cells among each group. However, a decrease in organelles associated with mucus secretion was seen with advancing age. By quantitative estimation, the average ratio Am:Ac of all groups had significant difference, P=0.000. The average ratio Am:Ac of the elderly group was significantly lower than that of the younger group, P=0.000. 3. Estimation of the content of MDA by TBA method in the gastric mucosa had no significance among all the groups, P=0.402. Both in the elderly group and the oldest-old elderly group, the content of MDA in the gastric mucosa of was higher than in the younger group, however, there was no statistical difference.4. Quantitative determination of the content of NO by nitrate reductase in the gastric mucosa had no significance among all the groups, P=0.705. Both in the elderly group and the oldest-old elderly group, the content of NO in the gastric mucosa was higher than in the younger group, but no statistical difference was shown.5. By ELISA method we found that the gastric mucosal content of PGI2(P=0.036)、 PGE2(P=0.010)、Survivin (P=0.013)、 PTEN (P=0.026)、CGRP (P=0.003)、 COX-1(P=0.034)、COX-2(P=0.009)、caspase-9(P=0.035) were significantly reduced with increasing age, while the content of VEGF、HSP70、EGF、ZO-1、 caspase-3were reduced with increasing age but had no significant difference. Between the elderly and younger group, the gastric mucosal content of HSP70(P=0.045)、Survivin (P=0.021)、PTEN (P=0.031)、CGRP (P=0.013)、 PGE2(P=0.022)、COX-2(P=0.027)、caspase-9(P=0.008) in the elderly group were significantly lower than that in the younger group, while the content of VEGF、PGI2、ZO-1、EGF、COX-1、caspase-3had no significant difference. Between the oldest-old elderly group and the younger group, the content of VEGF (P=0.010)、HSP70(P=0.020)、PGI2(P=0.003). PGE2(P=0.001)、 Survivin (P=0.002)、PTEN (P=0.001)、CGRP (P=0.000)、ZO-1(P=0.005)、 EGF (P=0.040)、COX-1(P=0.004)、COX-2(P=0.001)、caspase-9(P=0.013) in the gastric mucosa in the oldest-old elderly group was significantly lower than that in the younger group.Conclusion:Our preliminary study showed that, with aging the thickness of the gastric antral mucosa has no degradation in performance, however, the density of pyloric glands, organelles associated with mucus secretion in human gastric pyloric cells are significantly decreased, indicating that in the elderly gastric antral mucosa and its functioning glands have deteriorated performance and morphology. With aging, the gastric mucosal content of MDA which reflects the degree of lipid peroxidation is increased; the content of CGRP and PGE2which reflect the ability to regulate mucosal blood flow is reduced; the content of Survivin and HSP70which anti-apoptotic are reduced; and the content of EGF which can promote the regeneration of the gastric mucous membrane is reduced too. With advancing age COX-2、caspase-9、and caspase-3which exist in the normal gastric mucosa and bioactive factors which can promote apoptosis like PTEN、caspase-、caspase-3are also reduced. The changes seen with aging in the bioactive factors mentioned above indicate that the gastric mucosal defense-repair mechanisms in older people is the result of a multifactorial interaction with multiple interlinks. |
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