Graduate School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China.
Department of Cardiology, Guang'anmen Hospital, Beijing, China.
Chin J Integr Med. 2020 Dec;26(12):897-904. doi: 10.1007/s11655-020-2856-6. Epub 2020 Dec 1.
OBJECTIVE: To explore whether Panax notoginseng saponins (PNS) exhibits heart protective effect in myocardial infarction (MI) rats and to identify the potential signaling pathways involved. METHODS: MI rats induced by ligating the left anterior descending (LAD) coronary artery were assigned to sham coronary artery ligation or coronary artery ligation. Totally 36 Sprague-Dawley rats were randomly divided into sham group (distilled water, n=9), MI group (distilled water, n=9), PNS group (PNS, 40 mg/kg daily, n=9) and fosinopril group (FIP, 1.2 mg/kg daily, n=9) according to a random number table. The left ventricular morphology and function were conducted by echocardiography. Histological alterations were evaluated by the stainings of HE and Masson. The serum levels of C reactive protein (CRP), tumor necrosis factor α (TNF-α), growth differentiation factor-15 (GDF-15) and the ratio of metalloproteinase-9 (MMP-9) and tissue inhibitor of MMP-9 (TIMP-1) were determined by ELISA. The levels of activating transcription factor 3 (ATF3), mitogen-activated protein kinase kinase 3 (MAP2K3), p38 mitogen-activated protein kinase (p38 MAPK), phosphorylation of p38 MAPK (p-p38 MAPK), transforming growth factor-β (TGF-β1), collagen I, nuclear factor kappa B p65 (NFκB p65), phosphorylation of NFκB p65 (p-NFκB p65), and phosphorylation of inhibitory kappa Bα (p-Iκ Bα) in hearts were measured by Western blot and immunohistochemical staining, respectively. RESULTS: PNS improved cardiac function and fibrosis in MI rats (P<0.05). The serum levels of CRP, TNF-α, GDF-15 and the ratio of MMP9/TIMP1 were reversed by PNS in MI rats. The expressions of TGF-β1, collagen I, MAP2K3, p38 MAPK, p-p38 MAPK, NFκB p65, p-NFκB p65, and p-IκBα were down-regulated, while ATF3 increased with the treatment of PNS (P<0.05). CONCLUSIONS: PNS may improve cardiac function and fibrosis in MI rats via regulating ATF3/MAP2K3/p38 MAPK and NFκB signaling pathways. These results suggest the potential of PNS in preventing the development of ventricular remodeling in MI rats.
目的：探讨三七总皂苷（PNS）对心肌梗死（MI）大鼠是否具有心脏保护作用，并确定潜在的相关信号通路。
方法：结扎左前降支（LAD）冠状动脉诱导 MI 大鼠，分为假手术结扎组或冠状动脉结扎组。36 只 Sprague-Dawley 大鼠按随机数字表法分为假手术组（蒸馏水，n=9）、MI 组（蒸馏水，n=9）、PNS 组（PNS，40mg/kg 每日，n=9）和福辛普利组（FIP，1.2mg/kg 每日，n=9）。通过超声心动图检测左心室形态和功能。通过 HE 和 Masson 染色评估组织学改变。通过酶联免疫吸附试验（ELISA）测定 C 反应蛋白（CRP）、肿瘤坏死因子-α（TNF-α）、生长分化因子-15（GDF-15）和基质金属蛋白酶-9（MMP-9）/组织抑制剂基质金属蛋白酶-1（TIMP-1）的血清水平。Western blot 和免疫组化染色分别检测心脏中激活转录因子 3（ATF3）、丝裂原活化蛋白激酶激酶 3（MAP2K3）、p38 丝裂原活化蛋白激酶（p38 MAPK）、磷酸化 p38 MAPK（p-p38 MAPK）、转化生长因子-β（TGF-β1）、胶原 I、核因子κB p65（NFκB p65）、磷酸化 NFκB p65（p-NFκB p65）和磷酸化抑制κBα（p-Iκ Bα）的水平。
结果：PNS 改善了 MI 大鼠的心脏功能和纤维化（P<0.05）。PNS 逆转了 MI 大鼠血清 CRP、TNF-α、GDF-15 和 MMP9/TIMP1 比值。TGF-β1、胶原 I、MAP2K3、p38 MAPK、p-p38 MAPK、NFκB p65、p-NFκB p65 和 p-Iκ Bα的表达下调，而 ATF3 随着 PNS 的治疗而增加（P<0.05）。
结论：PNS 通过调节 ATF3/MAP2K3/p38 MAPK 和 NFκB 信号通路，可能改善 MI 大鼠的心脏功能和纤维化。这些结果表明 PNS 具有预防 MI 大鼠心室重构发展的潜力。
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