【摘要】目的 探讨四味土木香散（STP）对压力超负荷性心肌肥厚大鼠的保护作用及机制。方法 第一部分：Wistar大鼠随机分为假手术（sham）组、模型（Mod）组、Mod+STP高、中、低剂量（STP-H、STP-M、STP-L）组、Mod+阳性药卡托普利（CAP）组，检测血压、超声心动图、HE及Masson染色。第二部分：Wistar大鼠随机分为sham组、Mod组、Mod+STP-H组、Mod+STP-H+miR-34a-5p激动剂（agomir）组、Mod+STP-H+Notch1抑制剂（DAPT）组，观察HE及Masson染色，RT-qPCR检测肿瘤坏死因子α（TNF-α）、白介素-6（IL-6）、核因子κB（NF-κB）、miR-34a-5p表达量，Western Blot检测Notch1、NICD1、hes1蛋白表达量。结果 第一部分：STP各剂量组均对压力超负荷心肌肥厚具有改善作用,其中高剂量治疗效果最佳。与Mod组比，STP-H组在8、10周时血压降低，心功能提高，细胞短轴直径及心肌纤维化降低，差异均有统计学意义（P＜0.05，P＜0.01）。第二部分：与Mod组比，STP-H组 TNF-α、IL-6、NF-κB、miR-34a-5p表达水平降低，Notch1、NICDI、hes1表达量升高，差异均有统计学意义（P＜0.05，P＜0.01）。与STP-H组相比，agomir组、DAPT组细胞短轴直径及心肌纤维化增加，TNF-α、IL-6、NF-κB、miR-34a-5p表达水平升高，Notch1、NICDI、hes1表达降低，差异均有统计学意义（P＜0.05，P＜0.01）。结论 STP可通过抑制miR-34a-5p的表达，同时靶向激活Notch1通路而改善压力超负荷性心肌肥厚，发挥心肌保护作用。

【Abstract】Objective To investigate the protective effect and mechanism of Siwei Tuxiang Powder (STP) in rats with pressure overload cardial hypertrophy. Methods Part I: Wistar rats were randomly divided into sham operation (sham) group, model (Mod) group, Mod+STP high, medium and low dose (STP-H, STP-M, STP-L) group, and Mod+positive drug captopril (CAP) group.Blood pressure, echocardiography, HE and Masson staining were measured. Part II: Wistar rats were randomly divided into sham group, Mod group, Mod+STP-H group, Mod+STP-H+miR-34a-5p agonist (agomir) group, Mod+STP-H+Notch1 inhibitor (DAPT) group.Observe HE and Masson staining, and detect the expression of tumor necrosis factorα（TNF-α）、Interleukin-6 (IL-6), nuclear factorκB（NF-κB)、miR-34a-5p by RT-qPCR，and the expression of Notch1, NICD1 and hes1 proteins were detected by Western blot. Results Part I: All dose groups of STP can improve cardiac hypertrophy caused by pressure overload, and high dose treatment has the best effect. Compared with Mod group, STP-H group had decreased blood pressure, improved cardiac function, decreased short axis diameter and myocardial fibrosis at 8 and 10 weeks, and the difference was statistically significant (P<0.05, P<0.01). Part II: Compared with Mod group, the expression levels of TNF-α、IL-6、NF- κB、miR-34a-5p decreased in STP-H group , and the expression levels of Notch1, NICDI and hes1 increased, with statistical significance (P<0.05, P<0.01). Compared with STP-H group, the diameter of cell short axis and myocardial fibrosis increased in agomir group and DAPT group , and the expression levels of TNF-α、IL-6、NF-κB、miR-34a-5p increased, and the expression of Notch1, NICDI and hes1 decreased, with statistical significance (P<0.05, P<0.01). Conclusion STP can improve cardial hypertrophy induced by pressure overload by inhibiting the expression of miR-34a-5p and targeting the activation of Notch1 pathway.

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内蒙古自治区科技计划基金项目(No.2020GG0238),内蒙古自治区自然科学基金项目(No.2020MS08139)