目的 研究厚朴酚改善链脲佐菌素（streptozotocin，STZ）诱导的1型糖尿病小鼠糖尿病心肌病（DCM）的作用机制。方法 采用STZ诱导的1型糖尿病小鼠模型，造模成功后分别ig给予厚朴酚10、20 mg/kg，连续给药12周。采用酶联免疫反应检测血清肌酸激酶（CK）、肌酸激酶同工酶（CK-MB）和乳酸脱氢酶（LDH）水平；采用苏木素-伊红（HE）染色和Masson染色观察心肌组织病理性损伤；采用实时荧光定量PCR（qRT-PCR）检测心肌组织肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6） mRNA表达；Western blotting法检测心肌组织丝裂原活化蛋白激酶（MAPK）信号通路中细胞外调节蛋白激酶（ERK）、c-Jun氨基末端激酶（JNK）和p38磷酸化水平和核转录因子-κB（NF-κB）信号通路中NF-κB抑制蛋白（IκB）表达水平。结果 与对照组比较，模型组小鼠心脏血清学功能性指标CK、CK-MB和LDH水平增高（P<0.05），心脏出现病理性损伤，伴随IL-6和TNF-α mRNA表达水平升高（P<0.05），ERK、JNK和p38磷酸化水平增加（P<0.05）以及IκB降解增多（P<0.01）。厚朴酚组小鼠CK、CK-MB和LDH水平降低，与模型组比较差异显著（P<0.05）。厚朴酚能够改善高血糖诱导的小鼠心脏血清学指标异常及组织病理学损伤，降低小鼠心肌组织中IL-6和TNF-α表达水平（P<0.05），缓解糖尿病引起的心肌组织炎症反应，抑制心肌组织中MAPK信号通路信号分子（ERK、JNK和p38）的磷酸化以及减少NF-κB信号通路中IκB降解，且厚朴酚20 mg/kg组较10 mg/kg组作用显著。结论 厚朴酚通过影响MAPK/NF-κB信号通路降低1型糖尿病小鼠心肌炎症反应并改善其心肌损伤。

Objective To investigate the protective effects and mechanism of magnolol on diabetic cardiomyopathy in type 1 diabetic mice. Methods Using type 1 diabetic mice induced by streptozotocin (STZ), the mice in the magnolol-treated groups were treated intragastrically (ig) with magnolol by the dose of 10 mg/kg or 20 mg/kg respectively. After 12-week treatment, animals were then euthanized. The levels of creatine kinase (CK), MB isoenzyme of creatine kinase (CK-MB) and lactate dehydrogenase (LDH) in serum were detected by enzyme-linked-immunosorbent serologic assay (ELISA). The histopathology of heart tissue was detected by hematoxylin and eosin (HE) and Masson staining. Inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) were evaluated by qRT-qPCR assay. The alteration of MAPK and NF-κB signaling pathway was detected by Western blotting. Results Compared with the control group, the mice in diabetic group showed a significantly increase in the level of CK, CK-MB and LDH in serum (P < 0.05), and cardiac pathological lesions were also observed. With the TNF-α and IL-6 mRNA expression in cardiac tissue increased (P < 0.05), extracellular regulated protein kinases (ERK), C-Jun N-terminal kinase (JNK) and P38 phosphorylation level, as well as IκB degradation, were significantly increased in type 1 diabetic mice model. Compared with the model group, the level of cardiac serum markers (CK, CK-MB, and LDH) of mice in the magnolol-treated groups was significantly decreased (P < 0.05). Also, magnolol can improve the abnormalities of serum indexes and histopathological damage induced by diabetes in mice. It reduced cardiac tissue TNF-α and IL-6 mRNA expression level (P < 0.05). In addition to IκB degradation, phosphorylation of ERK, JNK and p38 were inhibited by treatment with magnolol (P < 0.05). Moreover, the effect of dosage 20 mg/kg magnolol was significantly superior to 10 mg/kg magnolol on the reduction of IκB degradation in NF-κB signaling pathway (P < 0.05). Conclusion Magnolol could attenuate the inflammation-mediated diabetic myocardial injuries via inhibiting activation of MAPK/NF-κB signaling pathway.

国家自然科学青年基金项目（81600659）；温州市公益性科技计划项目（Y20160306）；温州市科技计划项目（Y20140687，Y20140683）