大蒜素调控JAK2/STAT3信号通路对大鼠慢性萎缩性胃炎的影响

Effect of Allicin Regulating JAK2/STAT3 Signaling Pathway on Chronic Atrophic Gastritis in Rat

目的:研究大蒜素对大鼠慢性萎缩性胃炎(chronic atrophic gastritis,CAG)的影响,探索其潜在的作用机制。方法:120只大鼠随机分为正常组、模型组、大蒜素组(10 mg·kg^(-1))、AG490组(5 mg·kg^(-1))、大蒜素(10 mg·kg^(-1))+AG490(5 mg·kg^(-1))组,每组24只,除正常组外,其余组大鼠均采用MNNG+雷尼替丁+饥饱失常饮食20周复合因素干预复制CAG大鼠模型,造模完成后给予相应药物干预,正常组和模型组灌胃等体积生理盐水,每天1次,疗程12周。中性红清除法测定胃黏膜血流量;HE染色观察胃黏膜病理学变化并进行评分;ELISA法检测血清胃泌素(gastrin,GAS)、胃动素(motilin,MTL)、生长抑素(somatostatin,SS)和胃黏膜肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-6(interleukin-6,IL-6)、IL-1β的水平;分光光度法检测胃黏膜丙二醛(malondialdehyde,MDA)含量和超氧化物歧化酶(superoxide dismutase,SOD)、过氧化氢酶(catalase,CAT)活性;Western blot检测胃黏膜Janus激酶2(janus kinase 2,JAK2)、p-JAK2、信号转导与转录激活因子3(/signal transducer and activator of transcription 3,STAT3)、p-STAT3、高迁移率族蛋白B1(high mobility group protein B1,HMGB1)的蛋白表达水平。结果:与模型组比较,各给药组大鼠胃黏膜血流量及GAS、SS、MTL含量明显升高,胃黏膜病理评分及TNF-α、IL-6、IL-1β、MDA水平明显降低,SOD、CAT活性明显升高,p-JAK2、p-STAT3、HMGB1蛋白相对表达量及JAK2、STAT3磷酸化水平明显降低,大蒜素+AG490组作用效果最好,差异均具有统计学意义(P<0.05)。HE染色显示,模型组大鼠胃黏膜厚度变薄,腺体排列紊乱、萎缩、数量减少,炎性细胞浸润,部分胃黏膜上皮呈现肠上皮化生,给药以后,上述病理变化得到明显改善。结论:大蒜素可减轻CAG大鼠胃黏膜病变,改善胃功能,其机制可能与抑制JAK2/STAT3信号通路活化进而抑制炎症反应和氧化应激损伤有关。

Objective:To study the effect of allicin on chronic atrophic gastritis(CAG)in rats and explore its potential mechanism of action.Method:120 rats were randomly divided into normal group,model group,allicin group(10 mg·kg^(-1)),AG490 group(5 mg·kg^(-1)),allicin group(10 mg·kg^(-1))+AG490 group(5 mg·kg^(-1)),with 24 rats in each group.Except for the normal group,all other groups of rats were treated with MNNG+ranitidine+hunger and satiety disorder diet for 20 weeks to replicate the CAG rat model.After the model was established,corresponding drug interventions were given.The normal group and model group were given equal volume of physiological saline by gavage once a day,The treatment period is 12 weeks.The blood flow of gastric mucosa was measured by neutral red clearance method;HE staining was used to observe the pathological changes of gastric mucosa and score them;ELISA was used to detect the level of serum Gastrin(GAS),motilin(MTL),somatostatin(SS)and tumor necrosis factor in gastric mucosa-α(TNF-α),Interleukin-6(IL-6),IL-1β;The content of malondialdehyde(MDA)and the activities of superoxide dismutase(SOD)and catalase(CAT)in gastric mucosa were measured by spectrophotometry;Western blot was used to detect the protein expression levels of Janus kinase 2(JAK2),p-JAK2,signal transducer and activator of transcription 3(STAT3),p-STAT3,and high mobility group protein B1(HMGB1)in gastric mucosa.Results:Compared with the model group,the blood flow of gastric mucosa and the contents of GAS,SS,MTL of rats in each administration group increased significantly,and the pathological score of gastric mucosa and TNF-α,IL-6,IL-1β.The MDA level was significantly reduced,the SOD and CAT activities were significantly increased,and the relative expression levels of p-JAK2,p-STAT3,and HMGB1 proteins,as well as the phosphorylation levels of JAK2 and STAT3,were significantly reduced.The allicin+AG490 group had the best effect,and the differences were statistically significant(P<0.05).HE staining showed that in the model group,the thickness of gastric mucosa became thinner,the gland arrangement was disordered,atrophied,the number was reduced,and inflammatory cells infiltrated.Some gastric mucosa epithelium showed intestinal metaplasia.After administration,the above pathological changes were significantly improved.Conclusion:Allicin can alleviate the pathological changes of gastric mucosa and improve gastric function in CAG rats.The mechanism may be related to inhibiting the activation of JAK2/STAT3 signaling pathway,thereby inhibiting inflammatory response and oxidative stress injury.