丹参配方颗粒对热毒血瘀证大鼠调节作用的代谢组学研究  

A Metabolomic Study on Regulatory Effect of Danshen Formula Granules on Rats with Heat Toxicity and Blood Stasis Syndrome

作　　者：赵新新 黄雪君[1,2,3] 甘海宁 肖观林[1,2,3] 赵自明 ZHAO Xinxin;HUANG Xuejun;GAN Haining;XIAO Guanlin;ZHAO Ziming(Guangzhou University of Chinese Medicine,Guangzhou Guangdong China 510405;The Second Traditional Chinese Medicine Hospital of Guangdong,Guangzhou Guangdong China 510095;Guangdong Provincial Key Laboratory of Research and Development in Traditional Chinese Medicine,Guangzhou Guangdong China 510095)

机构地区：[1]广州中医药大学,广东广州510405 [2]广东省第二中医院,广东广州510095 [3]广东省中医药研究开发重点实验室,广东广州510095

出　　处：《中医学报》2023年第7期1366-1378,共13页Acta Chinese Medicine

基　　金：广东省科技创新战略专项资金项目(2018B020207009)。

摘　　要：目的:通过观察丹参配方颗粒对血瘀证大鼠血液相关指标、腹主动脉病理和血清代谢物的影响探讨丹参配方颗粒抗热毒血瘀证的药效和代谢调控机制。方法:将36只SD大鼠按体质量均衡原则分为对照组、模型组、丹参标准汤剂组(0.54 g·kg^(-1))和丹参配方颗粒组(0.964 g·kg^(-1)),各给药组以20 mL·kg^(-1)的体积灌胃给药,对照组和模型组灌胃等体积去离子水,每天1次,连续14 d。于给药第13天,除对照组外,其余组大鼠均复制热毒血瘀模型。末次给药后1~2 h,测大鼠肛温;全自动血凝分析仪检测凝血酶原时间(prothrombin time,PT)、凝血酶时间(thrombin time,TT)、活化部分凝血活酶时间(activated partial thromboplastin time,APTT)的水平;ELISA检测血浆白细胞介素-1β(interleukin-1β,IL-1β)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、纤维蛋白原(fibrinogen,FIB)、血栓素B2(thromboxane B2,TXB_(2))、6-酮前列腺素F1α(6-ketone-prostaglandin 1α,6-keto-PGF1α)的水平;HE染色观察腹主动脉血管壁病理变化;采用超高效液相色谱四级杆串联飞行时间质谱仪建立大鼠血清代谢指纹图谱,通过主成分分析(principal components analysis,PCA)、正交偏最小二乘判别分析(orthogonal partial least squares-discriminant analysis,OPLS-DA)筛选血清潜在代谢标志物,并进行代谢通路分析。结果:对照组大鼠血管壁完整;模型组大鼠动脉壁血管内皮不完整,中层平滑肌排列紊乱、折皱;各给药组动脉病理损伤有不同程度的改善。与模型组比较,丹参配方颗粒组大鼠体温显著升高,TNF-α、IL-1β、TXB_(2)水平显著降低,APTT、TT显著延长,6-keto-PGF1α水平显著升高,差异均有统计学意义(P<0.05)。代谢组学分析显示,与模型组比较,鉴定出23个标志代谢物,筛选出10条代谢通路,丹参配方颗粒可通过调控亚油酸代谢、苯丙氨酸与酪氨酸和色氨酸生物合成、酪氨酸代谢3条通路防治热毒血瘀证�Objective:To observe the effects of Danshen Formulae Granules on blood related indexes,abdominal aorta pathology and serum metabolites in rats with blood stasis syndrome.Methods:According to the principle of body mass balance,36 SD rats were divided into control group,model group,Danshen Standard Decoction group(0.54 g·kg^(-1))and Danshen Formulae Granule group(0.964 g·kg^(-1)).Each group was given intragastric administration with the volume of 20 mL·kg^(-1),and the control group and model group were given the same volume of dehydrated water once a day for 14 days.On the 13th day of administration,except for the control group,all the rats in the other groups replicated the model of heat-toxin and blood stasis.The anal temperature of rats was measured 1 to 2 hours after the last administration.The levels of prothrombin time(PT),thrombin time(TT)and activated partial thromboplastin time(APTT)were detected by automatic coagulation analyzer.The levels of interleukin-1β(IL-1β),tumornecrosisfactor-α(TNF-α),fibrinogen,FIB,thromboxane2,TXB2 and 6-ketone-prostaglandin1α(6-keto-PGF1α)in plasma were measured by ELISA,and the pathological changes of abdominal aorta were observed by HE staining.The serum metabolic fingerprint of rats was established by ultra high performance liquid chromatography four-stage tandem time-of-flight mass spectrometer.The serum potential metabolic markers were screened by principal component analysis(PCA)and orthogonal partial least square discriminant analysis(OPLS-DA),and the metabolic pathway was analyzed.Results:The vascular wall of the control group was intact,the vascular endothelium of the arterial wall of the model group was incomplete,the middle smooth muscle was disordered and wrinkled,and the pathological changes of each treatment group were improved in varying degrees.Compared with the model group,the body temperature of the rats in the Danshen Formulae Granule group increased significantly,the levels of TNF-α,IL-1βand TXB2 decreased significantly,the levels of APTT and TT p

关 键 词：热毒血瘀证 丹参配方颗粒 代谢组学 血瘀证 凝血功能 大鼠 

分 类 号：R285.5[医药卫生—中药学]