基于PPII3KK/Akt信号通路探讨化痰祛瘀方治疗痰瘀互结证冠状动脉粥样硬化性心脏病作用机制  

Mechanism of Huatan Quyu Formula in the Treatment of Coronary Heart Disease with Phlegm-Blood Stasis Syndrome Through the PI3K/Akt Signaling Pathway

作　　者：韩佳 杜鸿瑶 鲁静 潘晔 HAN Jia;DU Hongyao;LU Jing;PAN Ye(Tangshan Hospital of Traditional Chinese Medicine,Tangshan,Hebei,China 063000)

机构地区：[1]河北省唐山市中医医院,河北唐山063000

出　　处：《中国药业》2025年第7期59-64,共6页China Pharmaceuticals

基　　金：河北省中医药管理局中医药类科研计划课题[2022548]。

摘　　要：目的探讨化痰祛瘀方治疗痰瘀互结证冠状动脉粥样硬化性心脏病(CHD)的作用机制。方法将30只大鼠随机分为空白对照组(A组),模型对照组(B组),化痰祛瘀方低、中、高剂量组(C_(1)组、C_(2)组、C_(3)组),各6只。B组、C_(1)组、C_(2)组、C_(3)组大鼠喂食高脂饲料8周后腹腔注射垂体后叶素30 U/kg以建立CHD模型,A组大鼠正常饮食8周后腹腔注射等量蒸馏水。之后C_(1)组、C_(2)组、C_(3)组大鼠分别灌胃25,50,75 mg/(kg·d)化痰祛瘀方,A组、B组大鼠灌胃等量蒸馏水,连续4周。采用超声心动图检测仪检测各组大鼠的心功能指标[左室射血分数(LVEF)、左室舒张末期内径(LVEDd)、左室收缩末期内径(LVESd)、缩短分数(FS)];采用苏木精-伊红(HE)染色法评估大鼠心肌组织的病理学损伤程度;采用自动生化分析仪检测血脂指标[总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)]及心肌和内皮损伤程度指标[内皮素-1(ET-1)、肌酸激酶MB型同工酶(CK-MB)、心肌肌钙蛋白T(c Tn T)]水平;采用酶联免疫吸附试验(ELISA)法检测炎性因子[肿瘤坏死因子-α(TNF-α)、白细胞介素1β(IL-1β)、白细胞介素6(IL-6)]水平;采用免疫印迹(Western blot)法检测心肌组织中B淋巴细胞瘤2(Bcl-2)、Bcl-2相关X蛋白(Bax)、裂解胱天蛋白酶3(c-caspase-3)、磷脂酰肌醇-3-激酶(PI3K)、磷酸化PI3K(p-PI3K)、丝氨酸/苏氨酸蛋白激酶(Akt)、磷酸化Akt(p-Akt)的蛋白表达水平。结果与B组比较,C_(1)组、C_(2)组、C_(3)组大鼠的LVEDd和LVESd,血清TC,TG,LDL-C,CK-MB,c Tn T,ET-1水平,心肌组织TNF-α,IL-1β,IL-6水平及Bax,c-caspase-3,p-PI3K,p-Akt蛋白表达水平均显著降低(P<0.05);LVEF和FS,血清HDL-C水平,心肌组织Bcl-2蛋白表达水平均显著升高(P<0.05)。HE染色结果显示,C_(1)组、C_(2)组、C_(3)组大鼠的心肌细胞肿胀,心肌纤维紊乱,心肌细胞坏死、萎缩均得到改善。结论化痰祛瘀方�Objective To investigate the mechanism of Huatan Quyu Formula in the treatment of coronary heart disease(CHD)with phlegm-blood stasis syndrome through the PI3K/Akt pathway.Methods Thirty rats were randomly divided into the blank control(group A),model control(group B),and low-,medium-,high-dose Huatan Quyu Formula groups(groups C_(1),C_(2),C_(3)),with six rats in each group.Rats in groups B,C_(1),C_(2),and C_(3) were fed the high-fat diet for 8 weeks,and then they were intraperitoneally injected with 30 U/kg of posterior pituitary hormone to establish CHD models.After 8 weeks of normail diet,rats in group A were intraperitoneally injected with an equal volume of distilled water.The rats in groups C_(1),C_(2),and C_(3) were administered Huatan Quyu Formula at 25,50,and 75 mg/(kg·d)via gavage,respectively,while rats in groups A and B received equal volume of distilled water for 4 weeks.Cardiac function parameters[left ventricular ejection fraction(LVEF),left ventricular end-diastolic diameter(LVEDd),left ventricular end-systolic diameter(LVESd),fractional shortening(FS)]were measured by the echocardiography.Myocardial pathological damage was assessed by the hematoxylin-eosin(HE)staining.The levels of serum lipid indexes[total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C)],and myocardial/endothelial injury markers[endothelin-1(ET-1),creatine kinase-MB(CK-MB),cardiac troponin T(cTnT)]were analyzed by the automatic biochemical analyzer.The levels of inflammatory factors[tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6)]were detected by the enzyme-linked immunosorbent assay(ELISA).The expression levels of B-cell lymphoma 2(Bcl-2),Bcl-2-associated X protein(Bax),cleaved caspase-3(c-caspase-3),phosphatidylinositol-3-kinase(PI3K),phosphorylated PI3K(p-PI3K),serine/threonine-protein kinase(Akt),and phosphorylated Akt(p-Akt)protein were measured by the Western blot.Results Compared with those in group B,the LVEDd and LVESd

关 键 词：化痰祛瘀方 冠状动脉粥样硬化性心脏病 痰瘀互结证 磷脂酰肌醇-3-激酶 丝氨酸/苏氨酸蛋白激酶 

分 类 号：R932[医药卫生—生药学] R285.5[医药卫生—药学]