[Expression and function of apoptosis-related genes Bcl-2/Bax and Fas/Fas L in the course of stress ulcer].
OBJECTIVE
To investigate the correlation between the expressions of apoptosis-promoting gene Bax, apotosis-inhibiting gene Bcl-2, and Fas/FasL in gastric mucosa in the course of stress ulcer.


METHODS
Fifty-six rats were exposed to water immersion-restraint stress (WRS) and then randomly divided into 7 groups of 8 rats: WRS 2 h, RS 3.5 h, and 2 h, 5 h, 8 h, 12 h, and 24 h after termination of WRS. Another 8 rats were used as controls. The stomachs of rats were taken out at the above mentioned time points to observe histologically. Terminal deoxynucleatidyl transferase mediated dUTP nick and labeling (TUNEL) technique was used to examine the apoptotic cells in the gastric mucosa. The expression of Bcl-2/Bax protein was examined by immunohistochemical assay. In situ hybridization was used to detect the mRNA expression of Bcl-2, Fas, and FasL.


RESULTS
(1) Apototic cells were seen sporadically in the gastric mucosa of the control rats. The number of apoptotic cells began to increase since 2 hours after the beginning of WPS and reached its peak 5 hours after the termination of WRS. Since 8 - 12 hours after the termination of WRS the number of apoptosis began to decrease, however, still remained at a level significantly higher than the normal level (P < 0.05). (2) Fas mRNA and FasL mRNA were not expressed in the controls. Fas mRNA was detected 5 - 8 hours after the termination of WRS at the base of mucosa at a low level and disappeared 8 hours after the termination of WRS. FasL mRNA was detected since WRS 3.5h to 8 hours after the termination of WRS. (3) In normal gastric mucosa, Bcl-1 mRNA and protein were expressed in gastric gland zone at a middle level and Bax protein was expressed in the epithelial cells. In WRS rats Bax protein expression began to be detected in the epithelial cells lining the gastric pits since WRS 2 h, then increased, reached the peak 2 - 5 hours after the termination of WRS, and then gradually decreased and remained a little higher than normal level 24 hours later (P < 0.05). Bcl-2 expression began to decrease since the termination of WRS and then increased 8 - 12 hours after the termination of WRS and reached the normal level 24 hours later (P > 0.05). Correlation analysis showed that the expression of Bax protein was correlated with the quantity of apotosis in gastric mucosa.


CONCLUSIONS
The alterations of Bcl and Bax may be responsible for the development of mucosa lesion and recovery. The expression of Fas/FasL has no effect on the gastric mucosa apoptosis related to WRS. Overexpression of Bcl-2 may inhibit the Fas/FasL induced apoptosis.
Liu
Jing
J
Department of Gastroenterology, Shanghai Hospital, Second Military Medical University, Shanghai 200433, China.
Li
Zhao-shen
ZS
Wan
Xin-jian
XJ
Wang
Wen
W
D000818:Animals; D017209:Apoptosis; D053222:Fas Ligand Protein; D005753:Gastric Mucosa / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013276:Stomach Ulcer / Q000378:metabolism*; D013312:Stress, Physiological / Q000378:metabolism*; D051028:bcl-2-Associated X Protein; D019014:fas Receptor / Q000235:genetics*
C494828:Bax protein, rat; D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D019014:fas Receptor