黄芪桂枝汤对慢性萎缩性胃炎大鼠血清胃泌素、胃动素表达的影响

Effects of Huangqi Guizhi Decoction on the expression levels of serum gastrin and motilin in rats with chronic atrophic gastritis

目的 观察黄芪桂枝汤对慢性萎缩性胃炎(CAG)大鼠血清胃泌素(GAS)、胃动素(MTL)表达的影响。方法 将60只SPF级SD大鼠适应性饲养1周,选10只大鼠正常饲养,剩余50只大鼠采用甲基硝基亚硝基胍(MNNG)综合法制造CAG疾病模型,建模成功后随机分为模型组、叶酸组及黄芪桂枝汤高、中、低剂量组。空白组及模型组大鼠予10 mL/kg蒸馏水灌胃,叶酸组予叶酸混悬溶液5 mg/kg灌胃,黄芪桂枝汤高、中、低剂量组分别予黄芪桂枝汤28 g/kg、14 g/kg、7 g/kg灌胃,每日1次,每周灌胃5天,休息2天。灌胃8周后,取大鼠下腔静脉血和胃组织,采用酶联免疫吸附法测定大鼠血清GAS、MTL含量,采用苏木素-伊红(HE)染色观察胃部病理情况,并进行胃黏膜病理评分。结果 与空白组比较,模型组大鼠血清GAS升高(P<0.05),MTL水平降低(P<0.05);与模型组比较,黄芪桂枝汤高、中剂量组大鼠血清GAS水平均降低(P<0.05),叶酸组血清MTL高于模型组(P<0.05);与叶酸组比较,黄芪桂枝汤高、中、低剂量组血清GAS、MTL水平均改善,但比较差异无统计学意义(P>0.05);黄芪桂枝汤高、中、低剂量组间血清GAS、MTL水平比较差异无统计学意义(P>0.05)。胃组织形态学观察显示,空白组大鼠胃黏膜光滑红润、黏液较多;模型组大鼠胃黏膜上遍布疣状突起、增生,黏膜暗沉泛白;叶酸组大鼠与模型组大鼠胃黏膜相比有所改善,多单粒增生;各中药组大鼠增生突起少,且呈单粒分布,黏膜较红润,其中黄芪桂枝汤高、中剂量组大鼠的胃黏膜较光滑红润、弹性较好,疣状突起、增生较少。胃黏膜病理学观察显示,空白组大鼠胃黏膜上皮柱状细胞完整,黏膜肌层排列呈内环外纵,细胞核分布有序;而模型组大鼠黏膜肌层出现炎性浸润,排列较紊乱;叶酸组大鼠胃黏膜上皮柱状细胞核散在,排列不紧密;黄芪桂枝汤高、中、低剂量组胃黏膜肌层炎性浸润情况与模型组相比呈减轻态势。病理评分:与空白组比较,模型组大鼠胃黏膜大体及镜下病理评分均升高(P<0.05);与模型组比较,叶酸组及黄芪桂枝汤高、中、低剂量组胃黏膜大体及镜下病理评分均降低(P<0.05)。叶酸组与黄芪桂枝汤高、中、低剂量组间各评分比较差异无统计学意义(P>0.05)。结论 黄芪桂枝汤可有效改善大鼠CAG的胃黏膜病变,降低血清GAS水平、升高MLT水平,起到治疗CAG的效果。

Objective To study the effects of Huangqi Guizhi Decoction on the expression levels of serum gastrin(GAS)and motilin(MTL)in rats with chronic atrophic gastritis(CAG).Methods Sixty Sprague-Dawley(SD)ratsin the specific pathogen-free(SPF)level were habituated for one week.Ten rats were normally fed(control group),and the remaining 50 rats were modeling for CAG by the synthesis method of methyl nitrosonitrosoguanidine(MNNG).CAG rats were randomly divided into model group,folic acid group,high-dose Huangqi Guizhi Decoction group,medium-dose Huangqi Guizhi Decoction group and low-dose Huangqi Guizhi Decoction group,with 10 rats per group.Rats in control group and model group were given 10 mL·kg^(-1)·d^(-1) distilled water by gavage,and those in the folic acid group were given 5 mg·kg^(-1)·d^(-1) folic acid suspension by gavage.Oral gavage of crude drug of Huangqi Guizhi Decoction at 28 g·kg^(-1),14 g·kg^(-1) and 7 g·kg^(-1) with the dose of 10 mL·kg^(-1) was given to rats of high-dose,medium-dose and low-dose Huangqi Guizhi Decoction group,respectively.Gavage was performed daily for 5 days per week,followed by 2 days off,for a total of 8 weeks.Inferior vena cava blood samples and gastric tissues were collected.Serum GAS and MTL were measured by enzyme-linked immunosorbent assay(ELISA).Pathological changes in rat stomach were evaluated by hematoxylin-eosin(HE)staining.Gastric mucosal pathology score was graded.Results Compared with those of control group,rats in model group presented significantly higher GAS and lower MTL levels(P<0.05).Compared with those of model group,serum GAS was significantly lower in rats of high-dose and medium-dose Huangqi Guizhi Decoction groups(P<0.05).Serum MTL in folic acid group was significantly higher than that of model group(P<0.05).Compared with those of folic acid group,serum GAS and MTL levels were improved by high-dose,medium-dose and low-dose Huangqi Guizhi Decoction,although no significant differences were detectable(P>0.05).There was no statistically significant difference in serum GAS and MTL levels among the high-dose,medium-dose and low-dose Huangqi Guizhi Decoction groups(P>0.05).Histological findings of rat gastric tissues showed smooth and red gastric mucosa with a large amount of mucus in control group.In rats of model group,the dark and white gastric mucosa was covered by verrucous protrusions and hyperplasia.Morphological changes in folic acid group were significantly improved,with granular hyperplasia being observed.Granular hyperplasia was observed in Huangqi Guizhi Decoction groups,with less protrusions and hyperplasia,and smooth and red gastric mucosa.The greatest alleviation of gastric mucosa histology was detected in high-dose and medium-dose Huangqi Guizhi Decoction groups.Pathological examination revealed an intact structure of columnar epithelium,circulating arrange of the middle part and external lining of the muscularis mucosae and regularly arranged cell nuclei.Inflammatory infiltration and disordered arrangement of the muscularis mucosae were observed in rats of model group.Scattered and loosely arranged nuclei of columnar epithelial cells were observed in rats of folic acid group.Inflammatory infiltration in the muscularis mucosae was dose-dependently alleviated by high-dose,medium-dose and low-dose Huangqi Guizhi Decoction.Both gross and microscopic pathological scores were significantly higher in rats of model group than those of control group(P<0.05),which,in folic acid group and high-dose,medium-dose and low-dose Huangqi Guizhi Decoction groups,were significantly lower than those of model group(P<0.05).No significant differences in gross and microscopic pathological scores were detected between folic acid group and high-dose,medium-dose and low-dose Huangqi Guizhi Decoction groups(P>0.05).Conclusion Huangqi Guizhi Decoction can effectively alleviate gastric mucosal lesion in CAG rats,which lowers serum GAS and increases MLT.