Abstract

Context

HuoXue QianYang QuTan Recipe (HQQR) is used to manage hypertension and cardiac remodelling, but the mechanism is elusive.

Objective

To determine the mechanism of HQQR on obesity hypertension (OBH)-related myocardial fibrosis.

Materials and methods

OBH models were prepared using spontaneously hypertensive rats (SHRs) and divided (n = 6) into saline, low-dose (19.35 g/kg/d) HQQR, high-dose (38.7 g/kg/d) HQQR, and valsartan (30 mg/kg/d) groups for 10 weeks. Systolic blood pressure (SBP), and Lee’s index were measured. Heart tissues were examined by histology. HQQR’s effects were examined on cardiac fibroblasts (CFs) stimulated with angiotensin II and treated with HQQR, a caspase-1 inhibitor, siNLRP3, and oeNLRP3.

Results

HQQR(H) reduced SBP (201.67 ± 21.00 vs. 169.00 ± 10.00), Lee’s index (321.50 ± 3.87 vs. 314.58 ± 3.88), and left ventricle mass index (3.26 ± 0.27 vs. 2.71 ± 0.12) in vivo. HQQR reduced percentage of fibrosis area (18.99 ± 3.90 vs. 13.37 ± 3.39), IL-1β (10.07 ± 1.16 vs. 5.35 ± 1.29), and inhibited activation of NLRP3/caspase-1/IL-1β pathway. HQQR also inhibiting the proliferation (1.09 ± 0.02 vs. 0.84 ± 0.01), fibroblast to myofibroblast transition (14.74 ± 3.39 vs. 3.97 ± 0.53), and collagen deposition (Col I; 0.50 ± 0.02 vs. 0.27 ± 0.05 and Col III; 0.48 ± 0.21 vs. 0.26 ± 0.11) with different concentrations selected based on IC₅₀ in vitro (all ps < 0.05). NLRP3 interference further confirmed HQQR inhibiting NLRP3 inflammasome signalling.

Conclusion

HQQR blunted cardiac fibrosis development in OBH and suppressed CFs proliferation by directly interfering with the NLRP3/caspase-1/IL-1β pathway.

中文翻译：

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活血千阳祛痰方通过抑制NLRP3炎症小体信号通路减轻肥胖高血压大鼠心脏纤维化

摘要

语境

活血千阳祛痰方（HQQR）用于治疗高血压和心脏重构，但机制尚不清楚。

客观的

探讨HQQR对肥胖性高血压（OBH）相关心肌纤维化的作用机制。

材料和方法

使用自发性高血压大鼠 (SHR) 制备 OBH 模型，并将 ( n  = 6) 分为生理盐水、低剂量 (19.35 g/kg/d) HQQR、高剂量 (38.7 g/kg/d) HQQR 和缬沙坦 ( 30 mg/kg/d) 组，持续 10 周。测量收缩压（SBP）和李氏指数。通过组织学检查心脏组织。HQQR 对用血管紧张素 II 刺激并用 HQQR、caspase-1 抑制剂、siNLRP3 和 oeNLRP3 治疗的心脏成纤维细胞 (CF) 的作用进行了检查。

结果

HQQR(H) 降低 SBP (201.67 ± 21.00 vs. 169.00 ± 10.00)、Lee 指数 (321.50 ± 3.87 vs. 314.58 ± 3.88) 和左心室质量指数 (3.26 ± 0.27 vs. 2.71 ± 0.12) 。HQQR 降低了纤维化面积的百分比（18.99 ± 3.90对13.37 ± 3.39）、IL-1β（10.07 ± 1.16对5.35 ± 1.29），并抑制了 NLRP3/caspase-1/IL-1β 通路的激活。HQQR 还抑制增殖（1.09 ± 0.02 vs. 0.84 ± 0.01）、成纤维细胞向肌成纤维细胞的转变（14.74 ± 3.39 vs. 3.97 ± 0.53）和胶原沉积（Col I；0.50 ± 0.02 vs. 0.27 ± 0.05 和 Col III； 0.48 ± 0.21对比0.26 ± 0.11)，根据体外IC ₅₀ 选择不同浓度（所有p s < 0.05）。NLRP3 干扰进一步证实了 HQQR 抑制 NLRP3 炎性体信号传导。

结论

HQQR 通过直接干扰 NLRP3/caspase-1/IL-1β 通路抑制 OBH 中心脏纤维化的发展并抑制 CFs 增殖。