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黄秋锦, 席建元, 刘秀梅, 陈邦第, 曾勇, 陈偶英.基于P2Y11/cAMP/PKA信号通路探讨复方钩藤降压片通过干预SHR炎症改善左心室肥厚的作用[J].湖南中医药大学学报英文版,2025,45(5):779-786.[Click to copy
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| 基于P2Y11/cAMP/PKA信号通路探讨复方钩藤降压片通过干预SHR炎症改善左心室肥厚的作用 |
| 黄秋锦,席建元,刘秀梅,陈邦第,曾勇,陈偶英 |
| (湖南中医药大学, 湖南 长沙 410208;湖南中医药大学第一附属医院, 湖南 长沙 410007) |
| 摘要: |
| 目的 探究复方钩藤降压片通过调节嘌呤能受体P2Y11亚型/环磷酸腺苷（cAMP）/蛋白激酶A（PKA）信号通路干预自发性高血压大鼠（SHR）炎症水平，改善左心室肥厚（LVH）的作用。方法 将60只SHR随机分为模型组（10 mL/kg无菌水灌胃+10 mL/kg生理盐水腹腔注射）、复方钩藤降压片组（10 mL/kg复方钩藤降压片混悬液灌胃+10 mL/kg生理盐水腹腔注射）、缬沙坦组（10 mL/kg缬沙坦混悬液灌胃+10 mL/kg生理盐水腹腔注射）、抑制剂组（10 mL/kg无菌水灌胃+10 mL/kg NF340储备液腹腔注射）、激动剂组（10 mL/kg无菌水灌胃+10 mL/kg NF546储备液腹腔注射），每组12只；另设12只WKY大鼠为对照组（10 mL/kg无菌水灌胃+10 mL/kg生理盐水腹腔注射）。均连续干预8周。监测大鼠尾动脉收缩压；计算心脏质量指数（HMI）、左心室质量指数（LMVI）；Western blot法检测心肌组织中P2Y11、p-PKA、白细胞介素-10（IL-10）蛋白表达水平；RT-PCR法检测cAMP、PKA、IL-10 mRNA表达水平；免疫组化法检测心肌组织中P2Y11、IL-10的阳性表达水平；ELISA法检测血清IL-10水平。结果 与对照组比较，模型组尾动脉收缩压及HMI、LVMI水平均升高（P＜0.01）；心肌组织P2Y11、p-PKA、IL-10蛋白及cAMP、PKA、IL-10 mRNA表达水平，P2Y11、IL-10阳性表达水平，血清IL-10含量均降低（P＜0.01）。与模型组比较，复方钩藤降压片组尾动脉收缩压及HMI、LVMI水平降低（P＜0.01）；心肌组织P2Y11、p-PKA、IL-10蛋白及cAMP、PKA、IL-10 mRNA表达水平，P2Y11、IL-10阳性表达水平，血清IL-10含量均升高（P＜0.05或P＜0.01）。与模型组比较，缬沙坦组尾动脉收缩压及HMI、LVMI水平降低（P＜0.01）；心肌组织P2Y11、IL-10蛋白及cAMP、IL-10 mRNA表达水平，血清IL-10含量均升高（P＜0.05或P＜0.01）。与模型组比较，激动剂组LVMI水平降低（P＜0.05）；心肌组织P2Y11、p-PKA、IL-10蛋白及cAMP、PKA、IL-10 mRNA表达水平，P2Y11、IL-10阳性表达水平，血清IL-10含量均升高（P＜0.05或P＜0.01）。结论 复方钩藤降压片可能通过上调P2Y11受体激活cAMP/PKA信号通路表达，改善SHR慢性炎症状态，从而降低SHR收缩压并改善左心室肥厚。 |
| 关键词: 自发性高血压 复方钩藤降压片 尾动脉收缩压 左心室肥厚 P2Y11/cAMP/PKA信号通路 |
| DOI：10.3969/j.issn.1674-070X.2025.05.001 |
| Received:October 12, 2024 |
| 基金项目:国家自然科学基金项目（82104842）；湖南省中医药科研计划项目（D2022086）；湖南省教育厅科学研究重点项目（22A0268）；长沙市自然科学基金项目（kq2208190）；中药粉体与创新药物省部共建国家重点实验室资助项目（2022FTKFJJ05）。 |
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| Effects of Fufang Gouteng Jiangya Tablet on alleviating left ventricular hypertrophy by intervening inflammation in SHR based on P2Y11/cAMP/PKA signaling pathway |
| HUANG Qiujin, XI Jianyuan, LIU Xiumei, CHEN Bangdi, ZENG Yong, CHEN Ouying |
| (Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410007, China) |
| Abstract: |
| Objective To explore the effects of Fufang Gouteng Jiangya Tablet (FFGTJYT) on alleviating left ventricular hypertrophy (LVH) by intervening inflammation through the purinergic receptor P2Y11 subtype/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling pathway in spontaneously hypertensive rats (SHRs). Methods Sixty SHRs were randomly divided into model group (intragastric administration of sterile water 10 mL/kg+intraperitoneal injection of saline 10 mL/kg), FFGTJYT group (intragastric administration of FFGTJYT suspension 10 mL/kg+intraperitoneal injection of saline 10 mL/kg), valsartan group (intragastric administration of valsartan suspension 10 mL/kg+intraperitoneal injection of saline 10 mL/kg), inhibitor group (intragastric administration of sterile water 10 mL/kg+intraperitoneal injection of NF340 reserve solution 10 mL/kg), and agonist group (intragastric administration of sterile water 10 mL/kg+intraperitoneal injection of NF546 reserve solution 10 mL/kg), with 12 rats in each group. Another 12 WKY rats were set as the control group (intragastric administration of sterile water 10 mL/kg+intraperitoneal injection of saline 10 mL/kg). All interventions were administered continuously for 8 weeks. Systolic blood pressure of tail artery of the rats was monitored. Heart mass index (HMI) and left ventricular mass index (LMVI) were calculated. Western blot was used to check the protein expression levels of P2Y11, p-PKA, and interleukin-10 (IL-10) in myocardial tissue. RT-PCR was used to examine the mRNA expression levels of cAMP, PKA, and IL-10. Immunohistochemistry was used to determine the positive expression levels of P2Y11 and IL-10 in myocardial tissue. ELISA was used to measure the serum content of IL-10. Results Compared with the control group, the model group showed significantly increased systolic blood pressure of tail artery, HMI, and LVMI (P<0.01). The protein expression levels of P2Y11, p-PKA, and IL-10 in myocardial tissue, as well as the mRNA levels of cAMP, PKA, and IL-10, the positive expression levels of P2Y11 and IL-10, and the serum level of IL-10 significantly decreased (P<0.01). Compared with the model group, the FFGTJYT group showed significant reductions in systolic blood pressure of tail artery, HMI, and LVMI (P<0.01). There was also a significant increase in the protein expression levels of P2Y11, p-PKA, and IL-10, positive expression levels of P2Y11 and IL-10, and serum content of IL-10 in myocardial tissue (P<0.05 or P<0.01). Compared with the model group, the valsartan group showed decreased systolic blood pressure of tail artery, HMI, and LVMI (P<0.01), and increased protein expression levels of P2Y11 and IL-10, mRNA expression levels of cAMP and IL-10, and serum content of IL-10 in myocardial tissue (P<0.05 or P<0.01). Compared with the model group, the agonist group had a lower LVMI expression (P<0.05), and increased protein expression of P2Y11, p-PKA, and IL-10, mRNA levels of cAMP, PKA, and IL-10, positive expression of P2Y11 and IL-10, and serum content of IL-10 (P<0.05 or P<0.01). Conclusion FFGTJYT can alleviate the chronic inflammatory state of SHR by upregulating the expression of P2Y11 receptor and activating the cAMP/PKA signaling pathway, thereby reducing the systolic blood pressure and alleviating LVH. |
| Key words: spontaneous hypertension Fufang Gouteng Jiangya Tablet systolic blood pressure of tail artery left ventricular hypertrophy P2Y11/cAMP/PKA signaling pathway |
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