Institute of Chinese Medicine, Heilongjiang University of Chinese Medicine, Harbin 150040, China.
Heilongjiang University of Chinese Medicine, Harbin 150040, China.
Biomed Pharmacother. 2022 Jan;145:112450. doi: 10.1016/j.biopha.2021.112450. Epub 2021 Nov 25.
The purpose of this study was to investigate the mechanism and effects of "Danggui-kushen" herb pair (DKHP) better than single drug in ischemic heart disease (IHD).
IHD model was established by left anterior descending branch of coronary artery in rats. Rats were randomized into six groups and oral administration for 7 days: control, model, Danshen dripping pills (DS) (5.103 g/kg), Danggui (DG) (2.7 g/kg), Kushen (KS) (2.7 g/kg) and DKHP (2.7 g/kg). Electrocardiogram (ECG), myocardial infarction and damage assessment, histological inspection analysis, and various biochemical indexes of myocardial tissue were measured to evaluate the myocardial damage and the protective effects of drugs. The inflammatory levels were identified by HE staining and serum cytokine, and the expression of hypoxia-inducible factor 1α (HIF-1α), inhibitor kappa B kinaseβ (IKKβ) and nuclear transcription factor kappa B (NF-κB) were measured by immunohistochemistry.
The results suggested that: compared with the control group, model group showed significantly myocardial tissue abnormalities, and increased levels of inflammatory cytokine. Treatment with drugs inhibited the increase of α-hydroxybutyrate dehydrogenase (α-HBDH), creatine kinase (CK), creatinekinase isoenzyme (CK-MB), interleukin 1 (IL-1) and interleukin 6 (IL-6). The results of immunohistochemical showed that drugs-treatment inhibited the expression of IKKβ and the P-p65, increased the expression of HIF-1α, which demonstrated that the anti-inflammatory effects of DKHP was achieved by suppressing of NF-κB signaling.
These observations indicated that DKHP can ameliorate myocardial injury better than single. And these are related to the inhibition of NF-κB and actives HIF-1α signaling.
本研究旨在探讨“当归- 苦参”药对(DKHP)优于单药治疗缺血性心脏病(IHD)的作用机制和效果。
通过结扎大鼠冠状动脉左前降支建立 IHD 模型。将大鼠随机分为六组,连续 7 天灌胃给药:对照组、模型组、丹参滴丸(DS)(5.103 g/kg)、当归(DG)(2.7 g/kg)、苦参(KS)(2.7 g/kg)和 DKHP(2.7 g/kg)。通过心电图(ECG)、心肌梗死和损伤评估、组织学检查分析以及心肌组织的各种生化指标来评估心肌损伤和药物的保护作用。通过 HE 染色和血清细胞因子鉴定炎症水平,通过免疫组化检测缺氧诱导因子 1α(HIF-1α)、抑制剂κB 激酶β(IKKβ)和核转录因子κB(NF-κB)的表达。
结果表明,与对照组相比,模型组心肌组织异常明显,炎症细胞因子水平升高。药物治疗抑制了α-羟丁酸脱氢酶(α-HBDH)、肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)、白细胞介素 1(IL-1)和白细胞介素 6(IL-6)的升高。免疫组化结果表明,药物治疗抑制了 IKKβ和 P-p65 的表达,增加了 HIF-1α的表达,这表明 DKHP 的抗炎作用是通过抑制 NF-κB 信号通路实现的。
这些观察结果表明,DKHP 能比单药更好地改善心肌损伤,这与抑制 NF-κB 和激活 HIF-1α信号通路有关。