泽泻调控细胞焦亡通路改善大鼠心肌纤维化机制

Rhizoma Alismatis Improves Myocardial Fibrosis in Rats via Modulation of Cell Pyroptosis Pathways

摘要

目的 以细胞焦亡通路为切入点,探究泽泻对盐酸异丙肾上腺素（ISO）所致SD大鼠心肌纤维化（MF）治疗作用及机制。方法 按照随机原则将大鼠分为对照（NC）组、模型（MF）组、卡托普利（CAP）组、泽泻低剂量（RAL）组、泽泻高剂量（RAH）组（每组8只）,采用ISO构建MF模型。检测血清中CK-MB、α-HBDH和LDH水平;HE染色和Masson染色观察大鼠心脏组织形态变化;Western blot法检测心脏组织中α-SMA、NLRP3、Caspase-1、GSDMD蛋白的表达水平。激光共聚焦观察大鼠心脏组织中Collagen Ⅰ蛋白表达。结果 经ISO诱导后,大鼠发生了显著的MF,主要表现为心脏的胶原纤维沉积且组织中细胞焦亡相关蛋白NLRP3、Caspase-1和GSDMD显著升高;经泽泻干预后,血清CK-MB、α-HBDH和LDH水平降低,心脏损伤及胶原沉积减轻,NLRP3、Caspase-1和GSDMD蛋白表达显著降低。结论 泽泻可有效缓解ISO所致的MF,其机制可能与细胞焦亡密切相关。

Abstract

Objective This study investigated the therapeutic efficacy of Rhizoma Alisma in isoproterenol(ISO)-induced myocardial fibrosis(MF) in SD rats, with a mechanistic focus on modulation of the pyroptotic pathway. Methods Rats were randomly allocated into five groups (n=8 per group): control(NC) group, MF group, Captopril(CAP) group, low-dose Rhizoma Alisma(RAL) group, and high-dose Rhizoma Alisma(RAH) group. MF was induced via ISO administration. Serum levels of CK-MB, α-HBDH, and LDH were quantified. Cardiac tissue morphology was assessed using HE and Masson staining. Western blot analysis determined the expression levels of α-SMA, NLRP3, Caspase-1, and GSDMD proteins, while laser confocal microscopy visualized Collagen I deposition in myocardial tissue. Results ISO induction triggered severe MF in rats, evidenced by histopathological collagen deposition and elevated NLRP3, Caspase-1, and GSDMD expression. Rhizoma Alisma treatment reduced serum levels of CK-MB, α-HBDH, and LDH, ameliorated tissue damage, downregulated collagen deposition, and significantly suppressed the expression of NLRP3, Caspase-1, and GSDMD. Conclusion Rhizoma Alisma demonstrates significant efficacy in attenuating ISO-induced MF, potentially through modulation of cell pyroptosis.

关键词

泽泻 / 心肌纤维化 / 细胞焦亡

Key words

Rhizoma Alisma / Myocardial fibrosis / Cell pyroptosis

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基金资助

河北省自然科学基金中医药联合基金重点项目（H2023406017）; 河北省教育厅高校重点学科建设项目（冀教高[2013]4号）; 承德医学院学科建设经费