穴位埋线对慢性萎缩性胃炎大鼠JAK 2-STAT 3信号转导通路相关因子表达的影响

Impact of Catgut Embedding Intervention on JAK 2-STAT 3 Signaling in Gastric Mucosa of Chronic Atrophic Gastritis Rats

目的:观察穴位埋线对慢性萎缩性胃炎(CAG)大鼠胃黏膜JAK 2-STAT 3通路相关蛋白p-JAK2、p-STAT 3、CyclinD 1、Bcl-2、SOCS 3表达的影响,探讨其改善CAG的机制。方法:SD大鼠随机分为空白组12只与造模组48只,采用自由饮用100μg/mL的N-甲基-N’-硝基-N-亚硝基胍溶液,并配合饥饱失常法复制CAG模型,造模成功后随机分为埋线组10只、模型组9只、自然恢复组10只。模型组大鼠予以立即剖杀,并取相关标本以备检,自然恢复组、空白组不予干预措施,埋线组大鼠予以双侧"足三里""脾俞"及"中脘"穴埋线治疗,每10d治疗1次,共治疗6次。采用肉眼和HE染色观察各组大鼠胃黏膜情况,采用Western blot法检测各组大鼠胃黏膜p-JAK 2、p-STAT 3、CyclinD 1、Bcl-2、SOCS 3表达。结果:肉眼、光镜下自然恢复组大鼠胃黏膜组织胃壁较薄,弹性较差,胃黏膜颜色较淡白,皱襞较少且较平,埋线组与自然恢复组相比,改善明显。与空白组相比,模型组、自然恢复组p-JAK 2、p-STAT 3、CyclinD 1、Bcl-2、SOCS 3表达均升高(P<0.01)。与模型组相比,自然恢复组p-JAK 2、p-STAT 3、CyclinD 1、Bcl-2、SOCS 3表达差异无统计学意义(P>0.05)。与自然恢复组相比,埋线组p-JAK 2、p-STAT 3、CyclinD 1、Bcl-2表达均降低(P<0.01),SOCS 3表达升高(P<0.01)。结论:穴位埋线疗法可能通过提高胃黏膜组织SOCS 3的表达,抑制JAK 2-STAT 3转导系统的异常激活,从而降低靶因子CyclinD 1、Bcl-2的表达水平,而发挥改善CAG的作用。

Objective To observe the impact of catgut embedding on histopathological changes and expression of phosphorylated-Janus kinase-2（p-JAK 2）,phosphorylated-signal transducer and activator of transcription 3（p-STAT 3）,Cyclin D 1,Bcl-2,and suppressor of cytokine signaling（SOCS）of the gastric mucosa in chronic atrophic gastritis（CAG）rats,so as to explore its mechanisms underlying improving CAG.Methods Forty-one SD rats were randomly divided into normal（n=12）,model（n=9）,natural recovery（n=10）and catgut embedding（n=10）groups.The CAG model was established by free drinking of N-methyl-N＇-nitro-N-nitroso-guanidine（MNNG）solution（100μg/mL）and irregular diet for 24 weeks.Catgut embedding was applied at bilateral＂Zusanli＂（ST 36）,＂Pishu＂（BL 20）and＂Zhongwan＂（CV 12）,once every 10 days,6 times altogether.The histopathological changes of the gastric mucosa were observed by naked eye and light microscope after H.E.staining.Wes-tern blot was used to detect the expression of p-JAK 2,p-STAT 3,CyclinD 1,Bcl-2 and SOCS 3 proteins in the gastric antrum tissue.Results After modeling,the regional gastric tissue showed pale thinner gastric wall,and poorer elasticity with fewer plica,congestion of blood vessels,reduction of regional glands with necrosis and disordered arrangement as well as evident hyperplasia of the connective tissue,which was evidently milder in the catgut embedding group.Compared with the normal group,the expression levels of p-JAK 2,p-STAT 3,CyclinD 1,Bcl-2,SOCS 3 proteins were significantly up-regulated in both model group and natural recovery group（P〈0.01）,without significant differences between the latter two groups（P〈0.05）.After catgut embedding intervention,the expression levels of p-JAK 2,p-STAT 3,Cyclin D 1,Bcl-2 proteins were considerably down-regulated（P〈0.01）,and that of SOCS 3 protein was notably further increased relevant to the natural recovery group（P〈0.01）.Conclusion Catgut embedding may improve pathological changes of gastric mucosa in CAG rats,which possibly associated with its effects in up-regulating gastric SOCS 3 protein expression and in inhibiting the activation of JAK 2-STAT 3 signaling pathway to reduce the expression of CyclinD 1 and Bcl-2 proteins.