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刘越美, 姚昆鹏, 蔡虎志, 邓旭, 彭丽琪, 陈新宇.基于PI3K/Akt信号通路探讨天牛止眩胶囊对自发性高血压大鼠心室重塑的影响[J].湖南中医药大学学报,2025,45(10):1816-1824[点击复制] |
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| 基于PI3K/Akt信号通路探讨天牛止眩胶囊对自发性高血压大鼠心室重塑的影响 |
| 刘越美,姚昆鹏,蔡虎志,邓旭,彭丽琪,陈新宇 |
| (湖南中医药大学第一附属医院, 国家中医心血管病临床医学研究中心分中心, 湖南 长沙 410007;湖南中医药大学, 湖南 长沙 410208) |
| 摘要: |
| 目的 基于磷脂酰肌醇3激酶/蛋白激酶B（PI3K/Akt）信号通路探索天牛止眩胶囊对自发性高血压大鼠心室重塑的影响。方法 选取30只7周龄SPF级自发性高血压大鼠（SHR）以及10只同周龄Wistar京都（WKY）大鼠。WKY大鼠为正常组（蒸馏水灌胃），SHR均分为模型组（蒸馏水灌胃）、天牛止眩组（22.6 mg/mL天牛止眩胶囊药物溶液灌胃）、依那普利组（0.11 mg/mL依那普利药物溶液+蒸馏水灌胃），每组均以10 mL/kg剂量每天灌胃3次。8周后测定体质量及基础血压后，取大鼠心肌组织及血清进行检测，测定左心室质量指数（LVMI），HE染色观察心肌组织病理变化，TUNEL染色评估心肌细胞凋亡情况，ELISA测定血清肾素（Renin）、血管紧张素Ⅱ（AngⅡ）、醛固酮（ALD）含量，Western blot及荧光定量PCR检测PI3K、Akt、核因子-κB（NF-κB）、B淋巴细胞瘤-2基因（Bcl-2）、Bcl-2相关X蛋白（Bax）、胱天蛋白酶（Caspase）-3、Caspase-9、原癌基因（FOS）、肿瘤蛋白P53（TP53）的蛋白及mRNA表达量。结果 与正常组比较，模型组血压、LVMI升高（P＜0.01）；心肌纤维排列松散，细胞肥大，数量减少，结缔组织增生明显；细胞凋亡率增高（P＜0.01）；血清Renin、AngⅡ、ALD含量增加（P＜0.05，P＜0.01）；心肌组织中Bax、Caspase-3、Caspase-9、FOS、TP53 mRNA表达升高（P＜0.01），PI3K、Akt、NF-κB、Bcl-2 mRNA降低（P＜0.01）；心肌组织中Bax、Caspase-3、Caspase-9、FOS、TP53蛋白表达升高（P＜0.01），p-PI3K、Akt、p-Akt、NF-κB、Bcl-2蛋白表达降低（P＜0.01）。与模型组比较，天牛止眩组、依那普利组血压下降（P＜0.01）；心肌细胞排列相对整齐，细胞形态相对正常，结缔组织增生减少；细胞凋亡率降低（P＜0.01）；血清Renin、AngⅡ、ALD含量降低（P＜0.01）；心肌组织中Bax、Caspase-3、Caspase-9、FOS、TP53 mRNA表达降低（P＜0.05，P＜0.01），PI3K、Akt、NF-κB、Bcl-2 mRNA升高（P＜0.05，P＜0.01）；心肌组织中Bax、Caspase-3、Caspase-9、FOS、TP53蛋白表达降低（P＜0.01），p-PI3K、p-Akt、NF-κB、Bcl-2蛋白表达升高（P＜0.01）。结论 天牛止眩胶囊在降压的同时，可改善原发性高血压导致的心室重塑，其作用机制可能与抑制肾素-血管紧张素-醛固酮系统（RAAS）激活，减少心肌细胞凋亡有关。PI3K/Akt信号通路可能是其发挥作用的重要信号通路。 |
| 关键词: 原发性高血压 天牛止眩胶囊 肾素-血管紧张素-醛固酮系统 PI3K/Akt信号通路 细胞凋亡 心室重塑 |
| DOI：10.3969/j.issn.1674-070X.2025.10.003 |
| 投稿时间：2025-05-31 |
| 基金项目:国家自然科学基金项目（81704061，81173213）；国家重大疑难疾病慢性心力衰竭中西医临床协作试点项目（国中医药办医政发〔2018〕3号）；湖南省中医药科研计划项目（B2023065）；湖南省中医药管理局心病“四时调阳”重点研究室建设专项（湘中医药函〔2020〕51号）。 |
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| Effects of Tianniu Zhixuan Capsule on ventricular remodeling in spontaneously hypertensive rats through the PI3K/Akt signaling pathway |
| LIU Yuemei, YAO Kunpeng, CAI Huzhi, DENG Xu, PENG Liqi, CHEN Xinyu |
| (The First Hospital of Hunan University of Chinese Medicine, Branch Center of National Clinical Research Center for Chinese Medicine Cardiology, Changsha, Hunan 410007, China;Hunan University of Chinese Medicine, Changsha, Hunan 410208, China) |
| Abstract: |
| Objective To explore the effects of Tianniu Zhixuan Capsule (TNZXC) on ventricular remodeling in spontaneously hypertensive rats (SHR) based on the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. Methods Thirty 7-week-old SPF SHRs and ten age-matched Wistar-Kyoto (WKY) rats were selected. The WKY rats served as the normal control group (intragastric administration of distilled water), while the SHRs were evenly divided into model group (intragastric administration of distilled water), TNZXC group (intragastric administration of 22.6 mg/mL TNZXC solution), and enalapril group (intragastric administration of 0.11 mg/mL enalapril solution plus distilled water). Each group received intragastric administration three times daily at a dose of 10 mL/kg. After eight weeks, body weight and basal blood pressure were measured. Then, the myocardial tissue and serum samples of rats were collected for analysis. The left ventricular mass index (LVMI) was measured. HE staining was used to observe the pathological changes in myocardial tissue, and TUNEL staining was employed to assess myocardial apoptosis. ELISA was used to determine the serum levels of renin (Renin), angiotensin Ⅱ (Ang Ⅱ), and aldosterone (ALD). The protein and mRNA expression levels of PI3K, Akt, nuclear factor-κB (NF-κB), B-cell lymphoma-2(Bcl-2), Bcl-2 associated X protein (Bax), Caspase-3, Caspase-9, FOS proto-oncogene protein (FOS), and tumor protein P53 (TP53) in the myocardial tissue were detected by Western blot and RT-PCR, respectively. Results Compared with the normal group, the model group exhibited increased blood pressure and LVMI (P＜0.01). The myocardial fibers were loosely arranged, with evident cardiomyocyte hypertrophy, reduced cell count, and significant connective tissue hyperplasia. The apoptosis rate was significantly elevated (P＜0.01), and the serum levels of Renin, Ang II, and ALD increased (P＜0.05, P＜0.01). The mRNA expression levels of Bax, Caspase-3, Caspase-9, FOS, and TP53 in myocardial tissue were upregulated (P＜0.01), while those of PI3K, Akt, NF-κB, and Bcl-2 were downregulated (P＜0.01). Additionally, the protein expression levels of Bax, Caspase-3, Caspase-9, FOS, and TP53 increased (P＜0.01), whereas those of p-PI3K, Akt, p-Akt, NF-κB, and Bcl-2 decreased (P＜0.01). Compared with the model group, the TNZXC and enalapril groups showed a decrease in blood pressure (P＜0.01). The myocardial cells were relatively neatly arranged, with relatively normal cell morphology and reduced connective tissue hyperplasia. The cell apoptosis rate decreased (P＜0.01), and the serum levels of Renin, Ang Ⅱ, and ALD were reduced (P＜0.01). The mRNA expression levels of Bax, Caspase-3, Caspase-9, FOS, and TP53 in the myocardial tissue were downregulated (P＜0.05, P＜0.01), while those of PI3K, Akt, NF-κB, and Bcl-2 were upregulated (P＜0.05, P＜0.01). Additionally, the protein expression levels of Bax, Caspase-3, Caspase-9, FOS, and TP53 decreased (P＜0.01), while those of p-PI3K, p-Akt, NF-κB, and Bcl-2 increased (P＜0.01). Conclusion TNZXC can lower blood pressure and ameliorate ventricular remodeling caused by essential hypertension. Its mechanism of action may involve suppression of the renin-angiotensin-aldosterone system (RAAS) activation and reduction of cardiomyocyte apoptosis. The PI3K/Akt signaling pathway is likely to be a key pathway mediating its effects. |
| Key words: essential hypertension Tianniu Zhixuan Capsule renin-angiotensin-aldosterone system PI3K/Akt signaling pathway apoptosis ventricular remodeling |
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