去甲二氢愈创木酸对大鼠慢性萎缩性胃炎的影响

目的 去甲二氢愈创木酸（nordihydroguaiaretic acid,NDGA）对多种肿瘤细胞具有抑制增殖和诱导凋亡作用,本文主要研究去甲二氢愈创木酸对大鼠慢性萎缩性胃炎（CAG）的预防作用,初步探讨其作用机制.方法 建立Wistar大鼠慢性萎缩性胃炎模型,将72只Wistar大鼠采用随机分组法平分为6组：正常组、模型组、三种不同剂量去甲二氢愈创木酸干预组和对照组.喂养24周后,处死大鼠,观察大鼠大体标本、胃黏膜HE染色后病理组织学改变,并采用免疫组化检测各组大鼠胃黏膜组织的5-脂氧合酶（5-LOX）、多肿瘤抑制基因（P16）蛋白的表达情况.结果 模型组萎缩性胃炎发生率较正常组明显高（77.8%vs 0%,P＜0.05）,说明造模成功.模型组较去甲二氢愈创木酸各剂量组慢性萎缩性胃炎发生率升高（77.8%vs 25%、27.3%、25%,P＜0.05）,阳性对照组与去甲二氢愈创木酸各组比较差异无统计学意义（30%vs 25%、27.3%、25%,P＞0.05）.5-LOX蛋白在模型组表达率与去甲二氢愈创木酸各组相比升高（44%vs25%、27%、25%,P＜0.05）.P16蛋白在模型组表达率与去甲二氢愈创木酸各组相比下降（66.7%vs 83.3%、81.8%、83.3%,P＜0.05）,而去甲二氢愈创木酸各组与阳性对照组差异无统计学意义（83.3%、81.8%、83.3%vs 80%,P＞0.05）.结论 去甲二氢愈创木酸能有效降低甲基硝基亚硝基胍（MNNG）诱导的大鼠萎缩性胃炎的发生,有逆转慢性萎缩性胃炎的预防作用.去甲二氢愈创木酸降低MNNG诱导的大鼠萎缩性胃炎的发生机制可能与下调5-脂氧合酶表达及上调多肿瘤抑制基因P16蛋白表达有关.

Effect of nordihydroguaiaretic acid on chronic atrophic gastritis in rats

Objective To study the preventive effect of lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) on chronic atrophic gastritis (CAG). Methods To construct CAG rat model, 72 male rats were randomly divided into 6 groups, including normal group, CAG model group, NDGA group with different dose and positive groups (folacin). After feeding for 24 weeks, all rats were executed, their stomach mucous membrane was picked out and stained with H.E. The expression of 5-LOX and P16 protein in mucous membrane epithelia cells were detected by immunohistochemistry. Results The CAG incidence rate in model group was significant higher than normal group (77.8% vs 0% , P ＜0. 05), which indicated that C AG model rat was successfully established. The CAG incidence rate of model group was significantly higher than NDGA groups (77.8% vs 25% ,27.3% ,25%, P＜0.05), while no significant difference was found between positive group and NDGA groups (30% vs 25% ,27.3% ,25% , P＞0.05) .The expression of 5-lox in model group was higher than NDGA groups (44% vs 25% ,27% ,25%, P＜0.05). The expression of P16 protein in model group was lower than NDGA groups (66.7% vs 83.3% ,81.8% ,83.3%,P＜0.05) , and there were no significant differences between NDGA groups and positive group (83. 3%,81.8% ,83.3% vs 80%, P＞0.05). Conclusions NDGA could prevent the occurrence of N-ethyl-N-nitro-N nitrosoguanidine-induced chronic atrophic gastritis in rat. NDGA could down-regulate the expression of 5-LOX and up-regulate the expression of P16 in stomach mucous membrane of N-ethyl-N-nitro -N-nitrosoguanidine-induced chronic atrophic gastritis in rat.