基于血清代谢组学探讨养筋解毒汤对糖尿病周围神经病变大鼠的作用机制

Serum Metabonomics Study on Mechanism of Action of Yangjin Jiedu Decoction on Diabetic Peripheral Neuropathy Rats

目的 基于血清代谢组学研究养筋解毒汤治疗糖尿病周围神经病变(Diabetic peripheral neuropathy,DPN)大鼠的作用机制。方法 将24只SPF级雄性SD大鼠按随机数字表法分为对照组、模型组、养筋解毒汤组,每组各8只,除对照组外,其余各组给予大鼠高脂高糖饲料饲喂8周,之后腹腔注射链脲佐菌制备DPN模型,采用体质量、体长、BMI指数和空腹GLU水平验证模型,模型成功后继续高脂高糖饲料饲喂8周后给予相应药物灌胃给药,2次/d,连续8周。采用空腹GLU水平评价疗效,采集大鼠血液分离血清利用非靶向代谢组学技术,通过主成分分析(PCA)、正交偏最小二乘法判别分析(OPLS-DA),结合t检验、变量重要性投影及差异倍数值筛选差异代谢物及可能的代谢通路。结果 经养筋解毒汤干预后与模型组比较,DPN大鼠血糖水平明显降低(P<0.01)。差异代谢物脯氨酸-亮氨酸(Pro-leu)、脯氨酸-异亮氨酸(Pro-Ile)、亮氨酸-酪氨酸(Leu-Tyr)等148种代谢物水平发生变化,同时对类固醇激素生物合成、精氨酸和脯氨酸代谢、甘氨酸、丝氨酸和苏氨酸代谢等代谢通路产生影响。结论 养筋解毒汤对DPN大鼠具有一定的治疗疗效,其机制可能与调节氨基酸及皮质激素代谢等有关。

Objective To study the mechanism of Yangjin Jiedu Decoction(YJJD)in treating diabetic peripheral peripheral neuropathy(DPN)rats based on serum metabolomics.Methods 24 male SPF-grade SD rats were randomly divided into a control group,a model group,and a YJJD group,with 8 rats in each group.Rats were fed with the high-fat and high-sugar diet for 8 weeks except for the control group,with streptozotocin(stz)injected intraperitoneally to make the DPN model.After 8 weeks of a high-fat and high-sugar diet,rats were given YJJD(0.248 g/kg),twice daily for 8 weeks.Blood samples were collected to measure the fasting blood glucose(Glu)of rats,and serum was isolated using non-targeted metabonomics.Principal component analysis(PCA)and orthogonal partial least squares discriminant analysis(OPLS-DA)combined with t-test,variable importance projection,and differential fold values to screen the differential metabolites and possible pathways.Results YJJD significantly decreased the blood glucose level of DPN rats compared with the control group.Through metabolomics,it was found that YJJD could obviously improve 148 different metabolites,including Pro-leu,Pro-Ile,and Leu-Tyr,and also influence steroid hormone biosynthesis,arginine and proline metabolism,glycine,serine and threonine metabolism and other metabolic pathways.Conclusion YJJD has a certain therapeutic effect on DPN rats,and its mechanism may be related to the regulation of amino acid and corticosteroid metabolism.