Effect of moluodan on gastric secretion in atrophic gastritis rats

目的：探究摩罗丹对胃分泌功能的影响以及其治疗萎缩性胃炎的机制。方法120只SPF级SD雄性大鼠采用随机数字表法随机分为正常对照组、萎缩性胃炎模型组、摩罗丹低剂量治疗组及摩罗丹高剂量治疗组，30只／组。正常对照组每天2 ml生理盐水灌胃；其余3组每天20 mol／L脱氧胆酸钠1 ml、2％水杨酸钠1 ml灌胃，每10天给予N-甲基-N′-硝基-N-亚硝基胍（MNNG）200 mg／kg灌胃1次，持续造模16周。模型成功后，正常对照组及模型组每天2 ml生理盐水灌胃；摩罗丹低剂量治疗组给予摩罗丹0.9 g· kg－1· d－1灌胃；摩罗丹高剂量治疗组给予摩罗丹1.8 g· kg－1· d－1灌胃，持续治疗12周，分别于治疗第4、8、12周末取材。观察摩罗丹治疗萎缩性胃炎的效果，同时检测胃黏膜的分泌功能，免疫组化方法测定大鼠胃黏膜胃泌素（GAS）分泌细胞（G细胞）及生长抑素（SS）分泌细胞（ D细胞）的变化情况，酶联免疫吸附测定法（ ELISA ）测定大鼠血清中GAS及SS 水平。结果与模型组相比，摩罗丹高剂量治疗组大鼠胃窦黏膜G、D细胞数在治疗8周后升高[（0.617±0.114）比（0.476±0.116）个／mm2，（0.504±0.084）比（0.369±0.148）个／mm2，均P＜0.05]，摩罗丹低剂量治疗组大鼠胃窦黏膜G、D细胞数在治疗12周后升高[（0.674±0.129）比（0.528±0.103）个／mm2，（0.526±0.087）比（0.371±0.058）个／mm2，均P＜0.05]；摩罗丹高剂量治疗组治疗8周、低剂量治疗组治疗12周后血清GAS高于模型组[（1.313±0.080）比（0.964±0.080） ng／ml，（1.202±0.124）比（0.909±0.054）ng／ml，均P＜0.01]；摩罗丹高、低剂量治疗组血清SS水平均在治疗8周后低于模型组[（2.376±0.199）、（2.238±0.155）比（2.605±0.183） ng／ml；均P＜0.05]。结论摩罗丹可通过修复萎缩性胃炎大鼠胃黏膜G、D细胞，升高血清GAS水平治疗萎缩性胃炎。Objective To investigate the effect of moluodan on gastric secretion and the underlying mechanism of moluodan in treating atrophic gastritis.Method According to the random number table , 120 healthy male specific-pathogen-free (SPF) Sprague-Dawley rats were divided into 4 groups: control group, model group , moluodan low-dose group , and moluodan high-dose group , with 30 rats in each group.The control group was administered with normal saline 2 ml/d by gavage , the other three groups were administered with 2%sodium salicylate 1 ml/d, 20 mol/L sodium deoxycholate 1 ml/d, and N-methyl-N′-nitro-N-nitrosoguanidine ( MNNG) 200 mg/kg for every 10 days.And 16 weeks later , the control group and model group were treated with normal saline 2 ml/d by gavage , meanwhile the moluodan low-dose group was treated with moluodan 0.9 g· kg-1 · d-1 and the high-dose group was treated with moluodan 1.8 g· kg -1 · d-1 , continuously for 12 weeks.Ten rats of each group were sacrificed at the end of 4, 8, 12 weeks.The effect of moluodan on atrophic gastritis was observed.The secretion function of gastric mucosa was assessed through detecting the numbers of gastrin-secreting cells (G cells) and somatostatin-secreting cell (D cells) in gastric mucosa using immunochemical staining , and measuring the serum levels of gastrin ( GAS ) and somatostatin (SS) using enzyme-linked immunosorbent assay (ELISA).Results After 8 weeks, the numbers of G and D cells in gastric mucosa in the moluodan high-dose group significantly increased compared with the model group [ ( 0.617 ±0.114 ) vs ( 0.476 ±0.116 ) cells/mm2 , ( 0.504 ±0.084 ) vs (0.369 ±0.148) cells/mm2 , both P<0.05];the numbers of G and D cells in gastric mucosa in the low-dose group increased after 12-week′s treatment[(0.674 ±0.129) vs (0.528 ±0.103) cells/mm2,(0.526 ± 0.087) vs (0.371 ±0.058) cells/mm2 ,both P<0.05].The serum GAS levels increased markedly after 8 weeks in the moluodan high-dose group and after 12 weeks in the low-dose group [ ( 1.313 ±0.080 ) ng/ml vs (0.964 ±0.080) ng/ml, (1.202 ±0.124) ng/ml vs (0.909 ±0.054) ng/ml, both P<0.01]; the serum SS levels in both high-and low-dose groups were significantly lower than in the model group after 8-week′s treatment[(2.376 ±0.199) ng/ml, (2.238 ±0.155) ng/ml vs (2.605 ±0.183) ng/ml, both P<0.05 ].Conclusion Moluodan may treat atrophic gastritis by repairing G and D cells in gastric mucosa and thus increasing serum levels of GAS.吴阶平医学基金会临床科研专项资助基金中文核心期刊要目总览(PKU)中国科技核心期刊(ISTIC)中国科学引文数据库(CSCD)342729-27339