环氧合酶-2抑制剂对盐酸诱导大鼠胃粘膜损伤后上皮细胞增殖和愈合的影响

Effects of cyclooxygenase-2 inhibitors on gastric epithelial cell proliferating and gastric healing following hydrochloric acid-induced injury in rats

目的 :探讨特异性和非特异性环氧合酶 - 2 (COX - 2 )抑制剂 ,对盐酸诱导胃粘膜损伤后上皮细胞增殖和损伤愈合的影响。方法 :大鼠胃内给予 0 6mol/LHCl 1mL后 ,胃内给予NS - 398或吲哚美辛 ,Westernblot和免疫组化法分析盐酸灌胃前、后胃粘膜COX - 2表达 ,免疫组化检测增殖细胞核抗原 (PCNA)评价上皮细胞的增殖状态 ,小格图纸法计算胃损伤指数 (LI)。结果 :盐酸灌胃后 ,COX - 2在胃粘膜表层上皮细胞和腺颈部成体干细胞高表达。盐酸灌胃后 2 4h ,NS - 3984 0mg/kg组及吲哚美辛组PCNA标记指数 (PCNA -LI)分别为 (2 2 72± 4 33) %和(2 1 98± 5 18) % ,明显低于对照组 (34 4 6± 3 6 1) % (P <0 0 5 ) ;NS - 3984mg/kg组和 4 0mg/kg组LI分别为 (1 2 8±0 5 8) %和 (1 16± 0 5 6 ) % ,显著高于对照组 (0 5 8± 0 2 4 ) % (P <0 0 5 )。结论 :COX - 2抑制剂抑制胃粘膜上皮细胞增殖 ,延迟大鼠胃粘膜损伤的愈合 ,提示COX - 2表达在胃粘膜再生过程中起重要作用。

AIM: To clarify the effects of specific and non-specific cyclooxygenase-2 (COX-2) inhibitors on gastric epithelial cell proliferating and gastric healing following acid-induced damage. METHODS: Male Sprague-Dawley rats were given 1 mL of 0.6 mol/L hydrochloric acid (HCl) into the stomach. Ten minutes after the administration of the acid,the animals were given NS-398 (COX-2 inhibitor) or indomethacin. Levels of COX-1 and COX-2 in the gastric mucosa before and after HCl-administration were analyzed using western blotting and immunohistochemical staining. Proliferating cell nuclear antigen (PCNA) was detected using immunohistochemistry for epithelial cell proliferation. Gastric lesion index (LI) was assessed using planimetry. RESULTS: Expression of COX-2 was enhanced mainly in surface epithelial cells and neck cells following HCl-administration. At 24 h following acid administration,PCNA labeling index (PCNA-LI) was (22.72±4.33) % and (21.98±5.18) % in the groups treated with 40 mg/kg of NS-398 and indomethacin respectively,which was significantly lower than that in the control group [ (34.46±3.61) %,P< 0.05 ]; LI was (1.28±0.58) % and (1.16±0.56) % in the groups treated with 4 mg/kg and 40 mg/kg of NS-398,respectively,which was significantly higher than that in the control group [ (0.58±0.24) %,P< 0.05 ]. CONCLUSIONS: The present study demonstrated that cyclooxygenase-2 inhibitors delayed gastric mucosal healing by suppressing expansion of the mucosal proliferative zone. These results provide evidence that cyclooxygenase-2 plays an important role in gastric mucosal regeneration.