铝碳酸镁对实验性胃溃疡的疗效及其机制探讨

沈飞1,2冀子中1陈淑洁2王岚2方燕飞2姒健敏2*

嘉兴市第一医院消化内科1(嘉兴市医学重点学科 胃肠病学 学科编号：04-Z-12)(314001)

浙江大学胃肠病研究所2

*本文通信作者，Email: sijm@zju.edu.cn

背景：铝碳酸镁已用于胃溃疡的治疗，但其具体机制尚不明确。目的：探讨铝碳酸镁对实验性胃溃疡大鼠的疗效及其作用机制。方法：建立实验性乙酸致大鼠胃溃疡模型，成模后分为对照组、铝碳酸镁低剂量组、铝碳酸镁高剂量组，分别给予0.9% NaCl溶液、880 mg·kg-1·d-1和1 230 mg·kg-1·d-1铝碳酸镁灌胃。14 d后，行大体评估，以HE、CD31、VG染色评估再生黏膜组织成熟度，AB-PAS染色、氨基己糖水平、免疫组化染色和血清表皮生长因子(EGF)、前列腺素(PG)E2评估功能成熟度。结果：与对照组相比，铝碳酸镁高剂量组溃疡指数(UI)明显降低(P<0.05)；铝碳酸镁低、高剂量组再生黏膜厚度增加(P<0.05)，囊状扩张腺体数量明显减少(P<0.01)，微血管密度(MVD)明显增加(P<0.01)，胶原纤维明显增多(P<0.05)；中性黏液分泌量和氨基己糖水平明显升高(P<0.01)，黏膜EGF、EGF受体(EGFR)和PGE2表达均明显增强(P<0.01)，血清EGF、PGE2水平明显升高(P<0.01)。结论：铝碳酸镁能明显提高溃疡再生黏膜组织和功能的成熟度，提高溃疡愈合质量，其机制可能为中和胃酸，增强黏液-HCO3-屏障，上调EGF、PGE2表达。

关键词胃溃疡；铝碳酸镁；溃疡愈合质量；治疗

Therapeutic Effect and Mechanism of Hydrotalcite on Experimental Gastric UlcerSHENFei1,2,JIZizhong1,CHENShujie2,WANGLan2,FANGYanfei2,SIJianmin2.1DepartmentofGastroenterology,JiaxingFirstHospital,Jiaxing,ZhejiangProvince(314001);2InstituteofGastroenterology,ZhejiangUniversity,Hangzhou

Correspondence to: SI Jianmin, Email: sijm@zju.edu.cn

Background: Hydrotalcite has been used in the treatment of gastric ulcer, but its mechanism is not clear. Aims: To investigate the efficacy and mechanism of hydrotalcite on experimental gastric ulcer in rats. Methods: Experimental acetic acid-induced gastric ulcer model was established in rats. Model rats were randomly assigned into control group, low and high dose hydrotalcite groups, and 0.9% NaCl solution, 880 mg·kg-1·d-1, 1 230 mg·kg-1·d-1hydrotalcite were intragastrically administrated, respectively. After 14 days, macroscopic examination was performed; and HE staining, CD31 staining and VG staining were used to evaluate the histological maturity, AB-PAS staining, level of hexosamine, immunohistochemical staining, serum levels of epidermal growth factor (EGF), prostaglandin E2(PGE2) were used to evaluate the functional maturity.Results: Compared with control group, ulcer index (UI) was significantly decreased in high dose hydrotalcite group (P<0.05). Thickness of restored mucosa was significantly increased (P<0.05), number of cystically dilated gland was significantly decreased (P<0.01), microvessel density (MVD), collagen fiber, secretion of mucus, level of hexosamine, expressions of EGF, EGR receptor (EGFR) and PGE2, serum levels of EGF and PGE2were significantly increased in low and high hydrotalcite groups (P<0.05,P<0.01). Conclusions: Hydrotalcite could obviously improve the histological and functional maturity of regenerative mucosa, as well as the quality of ulcer healing. The mechanism might be related to the neutralization of gastric acid, enhancement of mucus-HCO3-barrier and up-regulation of expressions of EGF and PGE2.

Key wordsStomach Ulcer;Hydrotalcite;Quality of Ulcer Healing;Therapy

胃溃疡因胃黏膜攻击因子与防御修复因子平衡失调而引发[1]。仅通过抑制胃酸分泌和(或)根除幽门螺杆菌(Hp)不足以完全消除溃疡底部炎症，难以实现高质量愈合[2]，容易导致复发。Si等[3]的研究发现，质子泵抑制剂治疗后溃疡年复发率为7.09%，在Hp感染患者中可达23.33%，根除Hp后复发率仍高达6.45%。以往铝碳酸镁主要用于治疗消化不良、胃酸过多等，现因其黏膜保护作用已用于治疗糜烂性食管炎、胃溃疡等。最初认为铝碳酸镁促进溃疡愈合的机制是中和胃酸，但近期有研究表明其对胃溃疡的治疗作用可能还存在其他途径[4]。本研究通过给予实验性胃溃疡大鼠铝碳酸镁，旨在探讨其对胃溃疡的疗效及其具体机制。……