目的 探讨香青兰总黄酮（TFDM）对阿霉素诱导的小鼠心脏毒性的影响及可能的作用机制。方法 将小鼠随机分为6组：对照组、模型组、地塞米松（阳性药，5 mg·kg^-1）组和TFDM低、中、高剂量（45、90、180 mg·kg^-1）组。从第1天开始给小鼠ig给药，第8天和第12天ip阿霉素10 mg·kg^-1以诱导小鼠心脏毒性模型。在第15天麻醉小鼠，小鼠监测超声心动图后被处死，采集血液、心脏样本。苏木精-伊红（HE）和Masson染色检测心脏病理变化；试剂盒法检测血清肌酸激酶同工酶（CK-MB）、乳酸脱氢酶（LDH）、丙二醛（MDA）、超氧化物歧化酶（SOD）、肿瘤坏死因子α（TNF-α）、白细胞介素（IL）-1β、IL-6水平；Western blotting检测内质网应激关键蛋白表达水平；免疫荧光法检测葡萄糖调节蛋白78（GRP78）和蛋白激酶RNA样内质网激酶（PERK）蛋白共定位情况。结果 与模型组比较，中、高剂量TFDM显著降低左心室收缩末期内径（LVIDs），升高左室射血分数（LVEF）和左心室短轴缩短率（LVFS）（P＜0.05、0.01）；TFDM显著改善心肌组织的病理损伤；高剂量TFDM显著降低小鼠血清中CK-MB、LDH、MDA含量（P＜0.05、0.01），显著升高SOD活性（P＜0.01）；TFDM高剂量显著降低血清TNF-α水平，中、高剂量显著降低血清IL-1β水平，低、中、高剂量显著降低血清IL-6水平（P＜0.01）；高剂量TFDM显著降低心脏组织GRP78蛋白表达水平，低、中、高剂量TFDM显著降低PERK和真核翻译起始因子2α激酶（eIF2α）的蛋白表达水平（P＜0.05、0.01）；TFDM显著降低GRP78和PERK的共定位。结论 TFDM可能通过调控GRP78/PERK信号通路，抑制内质网应激，从而改善阿霉素诱导的小鼠阿霉素心脏毒性。

Objective Effects of total flavonoids from Dracocephalum moldavica (TFDM) on doxorubicin-induced cardiotoxicity in mice and its possible mechanism were investigated.Methods Mice were randomly divided into six groups: control group, model group, dexamethasone (positive drug, 5 mg·kg^-1) group and TFDM low, medium, and high doses (45, 90 and 180 mg·kg^-1) groups. From the first day, mice were ig administered drugs, and on the 8th and 12th d, doxorubicin (10 mg·kg^-1) was ip to induce a mouse model of cardiotoxicity. On the 15th day, mice were anesthetized, and echocardiography was monitored before they were sacrificed. Blood and heart samples were collected. Hematoxylin-eosin (HE) and Masson staining were used to detect cardiac pathological changes, serum creatine kinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 levels were detected by kit method, Western blotting was used to detect the expression levels of key proteins in endoplasmic reticulum stress; immunofluorescence was used to detect the colocalization of glucose-regulated protein 78 (GRP78) and protein kinase RNA-like endoplasmic reticulum kinase (PERK) proteins.Results Compared with the model group, medium and high doses of TFDM significantly reduced left ventricular end-systolic diameter (LVIDs), increased left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) (P<0.05, 0.01); TFDM significantly improved myocardial tissue pathological damage; the content of CK-MB, LDH and MDA in the serum of the high-dose TFDM group was significantly reduced (P<0.05, 0.01), and SOD activity was significantly increased (P<0.01); High-dose TFDM significantly reduced TNF-α levels, medium and high doses significantly reduced IL-1β levels, and low, medium and high doses significantly reduced IL-6 levels (P<0.01); The expression levels of GRP78 protein in the high-dose TFDM group and PERK and eukaryotic translation initiation factor 2α kinase (eIF2α) proteins in the low, medium and high-dose groups were significantly decreased (P<0.05, 0.01); TFDM significantly reduced the co-localization of GRP78 and PERK.Conclusion TFDM may improve DOXinduced cardiotoxicity in C57BL/6J mice by regulating the GRP78/PERK signaling pathway, inhibiting endoplasmic reticulum stress.

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自治区卫生健康青年医学科技人才专项科研项目（WJWY-202326）；新疆维吾尔自治区自然科学基金资助项目（2023D01B47）；自治区公益性科研院所基本科研业务费资助项目（KY2024125）