活血清热解毒方通过JAK/STAT信号传导通路调控动脉粥样硬化的分子机制探讨  

Molecular Mechanism of Huoxue Qingre Jiedu Decoction on Regulating Atherosclerosis through JAK/STAT Signaling Transduction Pathway

作　　者：阮春黄 梁硕 孟毅[3] 刘志勇[3] Nguyen Xuan Huynh;Liang Shuo;Meng Yi;Liu Zhiyong(Henan University of Traditional Chinese Medicine,Henan,Zhengzhou 450003,China.)

机构地区：[1]河南中医药大学,河南郑州450003 [2]河南中医药大学第二临床医学院,河南中医药大学第二附属医院,河南郑州450002 [3]河南省中医院,河南郑州450002

出　　处：《中国中医急症》2023年第10期1728-1732,共5页Journal of Emergency in Traditional Chinese Medicine

基　　金：河南省中医药科学研究专项课题(20-21ZY1024)。

摘　　要：目的 观察活血清热解毒方对动脉粥样硬化(AS)的改善作用,从JAK/STAT信号传导通路探讨其改善炎症反应的作用机制。方法 雄性SPF级Wistar大鼠随机分为空白对照组、模型组、阳性对照组(阿托伐他汀钙6.07 mg/kg)、中药低剂量组(活血清热解毒方1.2 g/kg)、中药高剂量组(活血清热解毒方4.8 g/kg)。对照组给予普通饲料,其余采用高脂饮食饲养联合腹腔注射维生素D3(VD3)的方法复制AS大鼠模型,成功后给药,每日1次,共12周。HE染色检测胸主动脉病理变化,ELISA法检测血清白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)、白细胞介素-10(IL-10)、肿瘤坏死因子-α(TNF-α)、单核细胞趋化蛋白-1(MCP-1)水平,全自动生化分析仪检测血清脂质水平,Western blotting检测酪氨酸蛋白激酶2(JAK2)、信号转导和转录激活因子3(STAT3)、细胞因子信号传导抑制因子3(SOCS3)蛋白表达。结果 与空白对照组比较,模型组大鼠血清总胆固醇(TC)、甘油三酯(TAG)、低密度脂蛋白(LDL)、IL-6、IL-1β、TNF-α、MCP-1,主动脉JAK2、STAT3、SOCS3蛋白相对表达水平显著提高,血清HDL、IL-10水平显著降低(P <0.05);与模型组比较,阳性对照组、中药低剂量组、中药高剂量组大鼠血清TC、TAG、LDL、IL-6、IL-1β、TNF-α、MCP-1,主动脉JAK2、STAT3、SOCS3蛋白相对表达水平显著降低,血清HDL、IL-10水平显著升高(P <0.05);与阳性对照组比较,中药高剂量组大鼠血清TAG、LDL、IL-6、IL-1β、TNF-α,主动脉JAK2、STAT3、SOCS3蛋白相对表达水平明显降低,HDL水平显著升高(P <0.05)。结论 活血清热解毒方能够降低AS大鼠模型血清脂质水平,减少IL-6、IL-1β、TNF-α、MCP-1等炎症细胞因子的表达,其作用机制可能与抑制JAK2/STAT3信号通路,抑制SOCS3蛋白表达有关。Objective:To oserve the effect of Huoxue Qingre Jiedu Decoction on atherosclerosis(AS)and to explore its mechanism of improving inflammatory response from JAK/STAT signal transduction pathway.Methods:Male SPF grade Wistar rats were randomly divided into the blank control group,model group,positive control group(atorvastatin calcium 6.07 mg/kg),low dose group of traditional Chinese medicine(Huoxue Qingre Jiedu Decoction 1.2 g/kg),and high dose group of traditional Chinese medicine(Huoxue Qingre Jiedu Decoction 4.8 g/kg).The control group was given normal diet,and the rest were fed with a high fat diet combined with intraperitoneal injection of vitamin D3(VD3)to replicate the AS rat model.After successful modeling,the drug was administered once a day for a total of 12 weeks.The pathological changes of thoracic aorta were detected by hematoxylin-eosin(HE)staining,and serum IL-6,IL-10,TNF-α,MCP-1 and IL-1β were detected by ELISA.The level of serum lipids was detected by automatic biochemical analyzer,and the expression of JAK2,STAT3 and SOCS3 protein was detected by Western blotting.Results:Compared with the blank control group,the serum TC,TAG,LDL,IL-6,IL-1β,TNF-α,MCP-1,JAK2,STAT3,and SOCS3 proteins in the model group were significantly increased,while serum HDL and IL-10 levels were significantly decreased(P<0.05);compared with the model group,the serum TC,TAG,LDL,IL-6,IL-1β,TNF-α,MCP-1,JAK2,STAT3,and SOCS3 proteins in the positive control group,the low dose group of traditional Chinese medicine,and the high dose group of traditional Chinese medicine were significantly decreased,while serum HDL and IL-10 levels were significantly increased(P<0.05);compared with the positive control group,the serum TAG,LDL,IL-6,IL-1β,TNF-α JAK2,STAT3,and SOCS3 proteins in the high-dose group of traditional Chinese medicine were decreased significantly,while the HDL level increased significantly(P<0.05).Conclusion:Huoxue Qingre Jiedu Decoction can reduce the serum lipid level,IL-6,TNF-α,MCP-1,and IL-1β in AS rats.Its mechan

关 键 词：动脉粥样硬化 活血清热解毒方 炎症反应 JAK/STAT信号通路 大鼠 

分 类 号：R285.5[医药卫生—中药学]