湖南中医药大学学报2025,Vol.45Issue(5):779-786,8.DOI:10.3969/j.issn.1674-070X.2025.05.001
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
Effects of Fufang Gouteng Jiangya Tablet on alleviating left ventricular hypertrophy by intervening inflammation in SHR based on P2Y11/cAMP/PKA signaling pathway
摘要
Abstract
Objective To explore the effects of Fufang Gouteng Jiangya Tablet(FFGTJYT)on alleviating left ventricular hypertrophy(LVH)by intervening inflammation through the pu rinergie 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.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Key words
spontaneous hypertension/Fufang Gouteng Jiangya Tablet/systolic blood pressure of tail artery/left ventric-ular hypertrophy/P2Y11/cAMP/PKA signaling pathway分类
医药卫生引用本文复制引用
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,2025,45(5):779-786,8.基金项目
国家自然科学基金项目(82104842) (82104842)
湖南省中医药科研计划项目(D2022086) (D2022086)
湖南省教育厅科学研究重点项目(22A0268) (22A0268)
长沙市自然科学基金项目(kq2208190) (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). (2022FTKFJJ05)