乳腺癌相关肽在应激胃粘膜适应性保护中的作用

Role of the pS_2 in gastric mucosa adaptative cytoprotection from stress

目的 研究乳癌相关肽 (pS2 )在水浸束缚应激 (WRS)大鼠胃黏膜基因的表达变化 ,探讨其在应激胃黏膜适应性保护中的作用。方法 采用单次和重复水浸束缚应激制作模型 ,动态监测胃黏膜血流量 (GMBF) ,大体及光镜下观察黏膜损伤程度 (UI)及组织学变化 ,逆转录 多聚酶链反应 (RT PCR)检测pS2 基因表达变化 ,免疫组化染色进一步证实pS2 表达。结果 (1)单次应激造成胃黏膜广泛损伤 ,但损伤指数在 3d、5d、7d逐渐减小 ,至 7d降为 2 0 8% ,GMBF逐渐恢复 ,至 7d上升为正常94 5 % ,pS2 基因表达逐渐增强 (0 5 0± 0 13vs 0 70± 0 11,P <0 0 1) ,免疫组化染色计分为 0 95± 0 11vs 1 4 2± 0 0 4P <0 0 1;(2 )重复应激后胃黏膜产生适应性 ,胃黏膜血流量上升 ,损伤逐渐减轻 ,4次应激后 ,损伤指数降低为单次应激的 2 2 % ,胃黏膜血流量上升为正常 94 2 % ,并且 ,胃腺区细胞增殖 ,pS2基因表达增强 (0 37± 0 0 2vs 0 77± 0 0 1,P <0 0 1) ,免疫组织化学染色计分为 0 5 5± 0 0 4vs 2 4 6±0 0 8,P <0 0 1。结论 pS2

Objective To determine the expression of pS 2 (a member of trefoil peptides) in gastric mucosal of rats undergone WRS, and to probe the role of pS 2 in adaptive cytoprotection Methods Wister rats were exposed to single or repeated WRS for 4 h every other day for up to 6 days Gastric mucosal blood flow (GMBF) was measured by LDF 3 Flowmeter The degree of the gastric mucosal lesions (UI) was evaluated grossly and histologically The expression of pS 2 was determined by RT PCR and immunohistochemistry Results (1) WRS applied once produced numerous gastric mucosal erosions UI gradually declined and GMBF restored on 3 d、5 d after stress UI was reduced to 20 8% and GMBF increased up to 94 5% of normal value The expression of pS 2 was increased during the healing of stress induced ulceration The same results were observed by immunohistochemistry (0 50±0 13 vs 0 70±0 11, P <0 01) (2) With repeated WRS, the adaptative cytoprotection against stress was developed UI after four consecutive WRS was 22% of UI after one WRS GMBF after four consecutive was 94 2% of normal value Cell proliferation in the neck regions of gastric glands was activated The expression of pS 2 was increased by using RT PCR (0 37±0 02 vs 0 77±0 01, P <0 01) and immunohistochemistry (0 55±0 04 vs 2 46±0 08, P <0 01) Conclusion Increased expression of pS 2 could play an important role in adaptation of gastric mucose developed after repeated WRS