目的 探討香青蘭總黃酮（TFDM）對(duì)阿霉素誘導(dǎo)的小鼠心臟毒性的影響及可能的作用機(jī)制。方法 將小鼠隨機(jī)分為6組：對(duì)照組、模型組、地塞米松（陽(yáng)性藥，5 mg·kg^-1）組和TFDM低、中、高劑量（45、90、180 mg·kg^-1）組。從第1天開(kāi)始給小鼠ig給藥，第8天和第12天ip阿霉素10 mg·kg^-1以誘導(dǎo)小鼠心臟毒性模型。在第15天麻醉小鼠，小鼠監(jiān)測(cè)超聲心動(dòng)圖后被處死，采集血液、心臟樣本。蘇木精-伊紅（HE）和Masson染色檢測(cè)心臟病理變化；試劑盒法檢測(cè)血清肌酸激酶同工酶（CK-MB）、乳酸脫氫酶（LDH）、丙二醛（MDA）、超氧化物歧化酶（SOD）、腫瘤壞死因子α（TNF-α）、白細(xì)胞介素（IL）-1β、IL-6水平；Western blotting檢測(cè)內(nèi)質(zhì)網(wǎng)應(yīng)激關(guān)鍵蛋白表達(dá)水平；免疫熒光法檢測(cè)葡萄糖調(diào)節(jié)蛋白78（GRP78）和蛋白激酶RNA樣內(nèi)質(zhì)網(wǎng)激酶（PERK）蛋白共定位情況。結(jié)果 與模型組比較，中、高劑量TFDM顯著降低左心室收縮末期內(nèi)徑（LVIDs），升高左室射血分?jǐn)?shù)（LVEF）和左心室短軸縮短率（LVFS）（P＜0.05、0.01）；TFDM顯著改善心肌組織的病理?yè)p傷；高劑量TFDM顯著降低小鼠血清中CK-MB、LDH、MDA含量（P＜0.05、0.01），顯著升高SOD活性（P＜0.01）；TFDM高劑量顯著降低血清TNF-α水平，中、高劑量顯著降低血清IL-1β水平，低、中、高劑量顯著降低血清IL-6水平（P＜0.01）；高劑量TFDM顯著降低心臟組織GRP78蛋白表達(dá)水平，低、中、高劑量TFDM顯著降低PERK和真核翻譯起始因子2α激酶（eIF2α）的蛋白表達(dá)水平（P＜0.05、0.01）；TFDM顯著降低GRP78和PERK的共定位。結(jié)論 TFDM可能通過(guò)調(diào)控GRP78/PERK信號(hào)通路，抑制內(nèi)質(zhì)網(wǎng)應(yīng)激，從而改善阿霉素誘導(dǎo)的小鼠阿霉素心臟毒性。

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.

R285.5

自治區(qū)衛(wèi)生健康青年醫(yī)學(xué)科技人才專項(xiàng)科研項(xiàng)目（WJWY-202326）；新疆維吾爾自治區(qū)自然科學(xué)基金資助項(xiàng)目（2023D01B47）；自治區(qū)公益性科研院所基本科研業(yè)務(wù)費(fèi)資助項(xiàng)目（KY2024125）