胃黏膜保护剂替普瑞酮对慢性萎缩性胃炎大鼠热休克蛋白表达的影响

 目的研究胃黏膜保护剂对大鼠慢性萎缩性胃炎(chronic atrophic gastritis,CAG)修复过程中胃腺体细胞热休克蛋白(heat shock protein 70,HSP70)表达的影响,探索胃黏膜保护剂作用机制,并有可能为临床药物疗效提供新的评价指标。方法通过建立大鼠慢性萎缩性胃炎模型,进行胃黏膜保护剂(替普瑞酮)的逆转治疗实验,以免疫组织化学方法和Western blot方法,研究胃黏膜组织HSP 70的表达、组织含量和分布特点。结果①24周CAG组成功造模后,与正常大鼠比较,腺体变薄、肌层增厚,并伴大量炎症细胞浸润;经自然修复4周,发现胃黏膜腺体层增厚,肌层变薄,但仍伴有明显炎症细胞浸润;替普瑞酮逆转治疗4周,可见黏膜炎症减轻,腺体层明显增厚,肌层变薄,与自然修复组及生理盐水组对比,除肌层厚度,差异非常明显(P<0.001),接近正常组大鼠形态;②免疫组化结果发现,24周CAG组、28周CAG组及正常对照组中HSP 70以胞浆表达为主,而替普瑞酮组及生理盐水组HSP 70胞浆和胞核均有表达。通过阳性腺体数及灰度值的综合分析,替普瑞酮逆转治疗后,阳性腺体全层可见,HSP 70表达较各对照组明显增强(P<0.01);③Western blot定量研究证明,替普瑞酮逆转治疗后HSP 70含量增加极明显。结论胃黏膜保护剂替普瑞酮能明显促进HSP 70表达,其可能通过HSP 70参与的胃黏膜修复的病理生理过程发挥黏膜保护作用。

Effect of protective agent of gastric mucosa on expression of heat shock protein 70 in rats with chronic atrophic gastritis

OBJECTIVE To investigate the effect of protecting medicament of gastric mucosa on the expression of HSP 70 in rats with CAG and to elucidate the protective mechanism. METHODS CAG rats were treated with a protecting medicament of gastric mucosa. Western blot and immunohistochemistry were employed to determine the expression, contents and of distribution of HSP 70 in gastric mucosa. RESULTS ① HE analysis showed that the gland lay of CAG rats turned thinner and muscle lay became thicker with a lot of inflammation cells soakage; after natural repairing for 4 weeks, the gland lay got thicker and muscle lay turned thinner; after 24 weeks CAG rats were treated with teprenonc for 4 weeks, inflammation index decreased and the gland lay got thicker, which exhibited significant difference from 28 weeks CAG rats(natural repairing) and saline group(P<0.001), but were similar with normal group; ② Immunohistochemistry showed that HSP 70 was mainly expressed in the cytoplasm of the gastric gland cells in 24 weeks, 28 weeks CAG rats and normal control group, but it was found that HSP 70 was located in both of cytoplasm and nucleus in the groups treated with protective agent and saline. The results of counting positive glands and dust-color degree demonstrated that teprenone exhibited more significant expression of HSP 70 (P<0.01), compared with other groups; ③ A most significant increase for HSP 70 in the teprenone group was observed by Western blot analysis. CONCLUSION Protecting medicament of gastric mucosa (teprenone) significantly promoted the expression of HSP 70. HSP 70 was concerned with the process of the gastric mucosal repairment, and the protecting medicament of gastric mucosa may play the protective role in the press.