活心丸通过抑制异丙肾上腺素诱导的心力衰竭大鼠 TGF-β1/Smad2/3 通路减轻心肌纤维化。
Huoxin Pill () Attenuates Cardiac Fibrosis by Suppressing TGF-β1/Smad2/3 Pathway in Isoproterenol-Induced Heart Failure Rats.
机构信息
Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China.
Chen Keji Academic Thought Inheritance Studio, Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China.
出版信息
Chin J Integr Med. 2021 Jun;27(6):424-431. doi: 10.1007/s11655-020-2862-8. Epub 2020 Dec 22.
OBJECTIVE
To evaluate the effects of Huoxin Pill (, HXP) on cardiac fibrosis and heart failure (HF) in isoproterenol (ISO)-induced HF rats.
METHODS
Thirty Wistar rats were randomly divided into 5 groups including control, HF, isosorbide mononitrate (ISMN), HXP low (HXP-L), and HXP high (HXP-H) groups (n=6 for each group) according to the complete randomization method. Rats were pretreated with ISMN (5 mg/kg daily), low concentration of HXP (10 mg/kg daily) or high concentration of HXP (30 mg/kg daily) or equal volume of saline by intragastric administration for 1 week, followed by intraperitoneal injection of ISO (10 mg/kg, 14 days), and continually intragastric administrated with above medicines or saline for additional 6 weeks. The effects of HXP treatment on the cardiac function, heart weight index (HWI), pathological changes, and collagen content were further assessed. Moreover, the role of HXP on activation of transforming growth factor- β 1 (TGF-β 1)/Smads pathway was further explored using immunohistochemistry (IHC) and Western-blot assay.
RESULTS
HXP treatment significantly alleviated the decrease of ejection fraction (EF) and fractional shortening (FS), while decreased the elevation of left ventricular end-systolic volume (LVESV) in ISO-induced HF rats (P<0.05). Moreover, HXP treatment obviously attenuated the increase of HWI and serum level of creatine kinase MB (CK-MB, P<0.05), as well as pathological changes in ISO-induced HF rats. Further determination indicated that HXP treatment alleviated the elevation of collagen I and collagen III protein expression in cardiac tissues of ISO-induced HF rats. Furthermore, HXP treatment significantly down-regulated the increase of TGF-β 1 and p-Smad2/3 protein expression in cardiac tissues of HF rats (P<0.05), while did not affect the expression of total Smad2/3.
CONCLUSIONS
HXP attenuated heart failure and cardiac fibrosis in ISO-induced HF rats by suppression of TGF-β 1/Smad2/3 pathway.
目的
评价活心丸（HXP）对异丙肾上腺素（ISO）致心力衰竭（HF）大鼠心肌纤维化和心力衰竭的影响。
方法
30 只 Wistar 大鼠随机分为 5 组：对照组、HF 组、单硝酸异山梨酯（ISMN）组、HXP 低浓度（HXP-L）组和 HXP 高浓度（HXP-H）组（每组 6 只）。采用完全随机分组方法。大鼠用 ISMN（5mg/kg 每日）、HXP 低浓度（10mg/kg 每日）或 HXP 高浓度（30mg/kg 每日）或等容量生理盐水灌胃预处理 1 周，然后腹腔注射 ISO（10mg/kg，14 天），并继续灌胃上述药物或生理盐水 6 周。进一步评估 HXP 治疗对心功能、心脏重量指数（HWI）、病理变化和胶原含量的影响。此外，采用免疫组织化学（IHC）和 Western-blot 检测 HXP 对转化生长因子-β 1（TGF-β 1）/Smads 通路激活的作用。
结果
HXP 治疗可显著改善 ISO 致 HF 大鼠射血分数（EF）和短轴缩短率（FS）降低，左心室收缩末期容积（LVESV）升高（P<0.05）。此外，HXP 治疗明显减轻 ISO 致 HF 大鼠 HWI 和血清肌酸激酶 MB（CK-MB）升高（P<0.05），并改善病理变化。进一步检测表明，HXP 治疗可减轻 ISO 致 HF 大鼠心脏组织胶原 I 和胶原 III 蛋白表达升高。此外，HXP 治疗可显著下调 HF 大鼠心脏组织 TGF-β 1 和 p-Smad2/3 蛋白表达升高（P<0.05），而不影响总 Smad2/3 表达。
结论
HXP 通过抑制 TGF-β 1/Smad2/3 通路减轻 ISO 致 HF 大鼠心力衰竭和心肌纤维化。
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