| 钟 美,甘雨佳,黄 航,李婉芷,邹堂斌,孙建波.芹菜素调节Hippo-YAP信号通路对糖尿病心肌病大鼠心肌细胞凋亡的影响[J].,2024,(21):4014-4019 |
| 芹菜素调节Hippo-YAP信号通路对糖尿病心肌病大鼠心肌细胞凋亡的影响 |
| Effect of Apigenin on Cardiomyocyte Apoptosis in Diabetic Cardiomyopathy Rats by Regulating Hippo-YAP Signaling Pathway |
| 投稿时间：2024-06-05 修订日期：2024-06-18 |
| DOI：10.13241/j.cnki.pmb.2024.21.003 |
| 中文关键词: 芹菜素 Hippo-YAP信号通路 糖尿病心肌病 心肌细胞凋亡 |
| 英文关键词: Apigenin Hippo-YAP signaling pathway Diabetes cardiomyopathy Cardiomyocyte apoptosis |
| 基金项目:国家自然科学基金项目（82370969） |
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| 中文摘要: |
| 摘要 目的：芹菜素（QCS）调节Hippo-YAP信号通路对糖尿病心肌病（DCM）大鼠心肌细胞凋亡的影响。方法：将SD大鼠分为空白对照组（CK）组（体积生理盐水）、Model组（体积生理盐水）、QCS低剂量（QCS-L）组（20 mg/kg QCS）、QCS高剂量（QCS-H）组（40 mg/kg QCS）、QCS-H+维替泊芬（Verteporfin）（Hippo-YAP信号通路抑制剂）组（40 mg/kg QCS+10 mg/kg Verteporfin），每组10只。检测大鼠心功能、血糖（FPG）、空腹胰岛素（FINS）、胰岛素抵抗指数（HOMA-IR）、血清肌酸激酶（CK）、乳酸脱氢酶（LDH）、心肌肌钙蛋白（cTnI）水平及心肌组织超氧化物歧化酶（SOD）和过氧化氢酶（CAT）活性、丙二醛（MDA）含量；苏木精-伊红（HE）染色检测心肌组织形态；TUNEL法染色检测心肌组织细胞凋亡；蛋白印迹法（Western blot）检测心肌组织中B细胞淋巴瘤-2（Bcl-2）、Yes相关蛋白（YAP）、裂解凋亡蛋白酶-3（cleaved caspase-3）、Bcl-2相关X蛋白（Bax）、转录共激活因子（TAZ）蛋白表达。结果：与CK组相比，Model组大鼠心肌组织严重受损，心率（HR）、平均动脉压（MAP）、左室收缩压（LVSP）水平、心肌组织SOD和CAT活性、Bcl-2、YAP、TAZ蛋白表达降低，FPG、FINS、胰岛素抵抗指数（HOMA-IR）、血清肌酸激酶（CK）、乳酸脱氢酶（LDH）和心肌肌钙蛋白（cTnI）水平、心肌组织细胞凋亡率、MDA含量、cleaved caspase-3、Bax蛋白表达升高（P<0.05）；与Model组相比，QCS-L组和QCS-H组大鼠心肌组织形态有明显改善，HR、MAP、LVSP水平、心肌组织SOD和CAT活性、Bcl-2、YAP、TAZ蛋白表达升高，FPG、FINS、HOMA-IR水平、血清CK、LDH和cTnI水平、心肌组织细胞凋亡率、MDA含量、cleaved caspase-3、Bax蛋白表达降低（P<0.05）；Verteporfin可减轻QCS对DCM大鼠心肌细胞凋亡的改善作用。结论：QCS可降低DCM大鼠血糖水平和心肌细胞凋亡率，减轻氧化应激程度、心肌损伤，可能与激活Hippo-YAP信号通路有关。 |
| 英文摘要: |
| ABSTRACT Objective: The effect of apigenin (QCS) on cardiomyocyte apoptosis in diabetic cardiomyopathy (DCM) rats by regulating Hippo-YAP signaling pathway. Methods: SD rats were divided into blank control group (CK) group (volume normal saline), Model group (volume normal saline), QCS low dose (QCS-L) group (20 mg/kg QCS), QCS high dose (QCS-H) group (40 mg/kg QCS), QCS-H+Verteporfin(Verteporfin) (Hippo-YAP signaling pathway inhibitor) group (40mg/kg QCS+10 mg/kg Verteporfin), 10 rats in each group. Cardiac function, fasting plasma glucose (FPG), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR), serum creatine kinase (CK), lactate dehydrogenase (LDH), cardiac troponin I (cTnI), superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) in myocardial tissue were detected. The morphology of myocardial tissue was detected by hematoxylin-eosin (HE) staining. The myocardial cell apoptosis was detected by TUNEL staining. The expression of B cell lymphoma-2 (Bcl-2), Yes related protein (YAP), cleaved caspase-3 (cleaved caspase-3), Bcl-2 related X protein (Bax) and transcription coactivator (TAZ) in myocardial tissue were detected by Western blot (Western blot). Results: Compared with CK group, the myocardial tissue in Model group was severely damaged, and the heart rate (HR), mean arterial pressure (MAP), left ventricular systolic pressure (LVSP), the activity of SOD and CAT, and the expression of Bcl-2, YAP and TAZ protein were significantly decreased in model group, FPG, FINS, insulin resistance index (HOMA-IR), serum creatine kinase (CK), lactate dehydrogenase (LDH) and cardiac troponin (cTnI) levels, myocardial tissue cell apoptosis rate, MDA content, cleaved caspase-3 and Bax protein expression increased (P<0.05). Compared with Model group, the myocardial tissue morphology of rats in QCS-L group and QCS-H group were significantly improved, HR, MAP, LVSP levels, myocardial tissue SOD and CAT activity, Bcl-2, YAP, TAZ protein levels were increased, FPG, FINS, HOMA-IR levels, serum CK, LDH and cTnI levels, myocardial tissue cell apoptosis rate, MDA content, cleaved caspase-3, Bax protein expression decreased (P<0.05). Verteporfin could alleviate the improvement of QCS on cardiomyocyte apoptosis in DCM rats. Conclusion: QCS can reduce the blood glucose level and myocardial cell apoptosis rate in DCM rats, reduce the degree of oxidative stress and myocardial injury, which may be related to the activation of Hippo-YAP signaling pathway. |
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