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目的 观察能量稳态调节肽Adropin(ADR)对糖尿病心肌病(DCM)大鼠心肌纤维化的治疗作用，并探讨其可能作用机制。方法 取15只8周龄雄性SD大鼠，随机分为正常对照组(CON组)、高糖组(DCM组)、ADR干预组(ADR组)，每组5只。DCM组、ADR组以1%链脲佐菌素腹腔注射构建DCM模型，CON组不做任何处理；造模成功后ADR组予ADR 10μg/100 g腹腔注射，DCM组及CON组予生理盐水1 mL/100 g腹腔注射，1次/天，共注射8周。处死各组大鼠后取心肌组织，测算左心室/体重指数(LVW/BW)，观察心肌组织病理变化，检测心肌组织中炎症因子[肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)]、心肌组织纤维化指标[Ⅰ型胶原蛋白(ColⅠ)、Ⅲ型胶原蛋白(ColⅢ)]、转化生长因子β1(TGF-β1)/Smad信号通路相关蛋白[TGF-β1、Smad3、磷酸化的Smad3(p-Smad3)、磷酸化丝裂原活化蛋白激酶(p-p38)]。结果 与CON组相比，DCM组LVW、LVW/BW及心肌组织TNF-α、IL-6、ColⅠ、ColⅢ、TGF-β1、p-Smad3、p-p38相对表达量均升高(P均<0.05)。与DCM组相比，ADR组LVW、LVW/BW及心肌组织TNF-α、IL-6、ColⅠ、ColⅢ、TGF-β1、p-Smad3、p-p38相对表达量均降低(P均<0.05)。结论 ADR可改善DCM大鼠心肌纤维化程度，其机制可能与下调TGF-β1/Smad信号通路活性有关。
Abstract：Objective To investigate the therapeutic effects of Adropin(ADR) on myocardial fibrosis in rats with diabetic cardiomyopathy(DCM), and to explore its potential mechanisms. Methods Fifteen 8-week-old male SD rats were randomly divided into three groups: normal control group(CON group), high-glucose group(DCM group), and ADR intervention group(ADR group), with 5 rats in each group. The DCM models were established in the DCM group and ADR group through intraperitoneal injection of 1% streptozotocin, while the CON group received no treatment. After modeling, the ADR group was intraperitoneally injected with ADR at a dose of 10 μg/100 g, and the DCM group and CON group were intraperitoneally injected with normal saline at 1 mL/100 g, once daily for 8 consecutive weeks. After sacrificing the rats, myocardial tissues were collected to calculate the ratio of left ventricular weight(LVW) to body weight(LVW/BW), to observe pathological changes, and to detect the expression levels of inflammatory factors [tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6)], myocardial fibrosis markers [collagen type Ⅰ (Col Ⅰ) and collagen type Ⅲ (Col Ⅲ)], transforming growth factor-β1(TGF-β1)/Smad signaling pathway proteins [TGF-β1, Smad3, phosphorylated Smad3(phos-Smad3)], and p38 mitogen-activated protein kinase(p38) signaling pathway-related proteins [p38, phosphorylated p38(phos-p38)]. Results Compared with the CON group, the LVW, LVW/BW, and the expression levels of TNF-α, IL-6, Col Ⅰ, Col Ⅲ, TGF-β1, phos-p38, and phos-Smad3 in the DCM group significantly increased(all P<0. 05). After ADR intervention, compared with the DCM group, the LVW, LVW/BW, and the expression levels of TNF-α, IL-6, Col Ⅰ, Col Ⅲ, TGF-β1, phos-p38, and phos-Smad3 in the ADR group significantly decreased( all P<0. 05). Conclusion Adropin alleviates myocardial fibrosis in DCM rats, potentially by down-regulating the activity of p38 MAPK and TGF-β1/Smad signaling pathway.
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基本信息:
DOI：
中图分类号:R587.2
引用信息:
[1]陈鹏飞,王思梁,周灿,等.能量稳态调节肽Adropin对糖尿病心肌病大鼠心肌纤维化的治疗作用及其机制[J].山东医药,2025,65(12):11-14+18.
基金信息:
四川省医学青年创新科研课题计划项目（Q22063）; 四川省广安市广安区人民医院联合发展科研项目（2024LHFZ04）