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| Protective effect of Qishen Yiqi Dropping Pills on hypertensive myocardial injury by regulating IRE 1/XBP 1 signaling pathway |
| Hits 69 Download times 12 Received:September 11, 2024 |
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| DOI
10.11656/j.issn.1672-1519.2025.03.16 |
| Key Words
Qishen Yiqi Dripping Pill;“two kidneys and one clip” hypertensive rat;myocardial injury;IRE1/XBP1 pathway |
| Author Name | Affiliation | E-mail | | AN Yajuan | School of Integrated Traditional Chinese Medicine and Western Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
Department of Cardiology, Tianjin People's Hospital, Tianjin 300192, China | | | LIU Yue | Department of Cardiology, Tianjin People's Hospital, Tianjin 300192, China | liuyue0422@163.com | | GUAN Xiuju | School of Integrated Traditional Chinese Medicine and Western Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
Department of Cardiology, Tianjin People's Hospital, Tianjin 300192, China | | | WANG Xinshuang | School of Integrated Traditional Chinese Medicine and Western Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
Department of Cardiology, Tianjin People's Hospital, Tianjin 300192, China | | | WEI Liping | Department of Cardiology, Tianjin People's Hospital, Tianjin 300192, China | | | Qi Xin | Department of Cardiology, Tianjin People's Hospital, Tianjin 300192, China | |
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| Abstract
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| [Objective] To investigate the protective effect and mechanism of Qishen Yiqi Dripping Pills on the myocardium of hypertensive model rats. [Methods] A hypertensive rat model was established by the “two kidneys one clip”（2K1C） method. Four weeks after surgery，SD male rats were randomly divided into a sham operation group（Sham group，operated but without narrowing the left renal artery），a model group（Model group，administered an equal amount of physiological saline by gavage after successful modeling），a low-dose Qishen Yiqi Dropping Pills（QS-L） group，a high-dose group（QS-H） group[administered 270 and 540 mg/（kg·d） Qishen Yiqi Drop Pills by gavage after successful modeling]，and a 4-phenylbutyric acid group[4-PBA group，administered 500 mg/（kg·d） 4-PBA by gavage after successful modeling]，with 10 rats in each group. Administer once daily for 8 consecutive weeks. HWI of rats were measured. Blood pressure indicators of rats were measured by BP2000 tail blood pressure monitor every 2 weeks before and after surgery，including systolic blood pressure（SBP） and diastolic blood pressure（DBP）. Blood pressure and heart rate were also monitored every 2 weeks. After the end of drug administration，the cardiac systolic function indicators of each group of rats were detected by small animal echocardiography：left ventricular ejection fraction（LVEF），left ventricular fractional shortening（LVFS），left ventricular end systolic diameter（LVESD），and left ventricular end diastolic diameter（LVEDD）. Enzyme linked immunosorbent assay（ELISA） was used to detect angiotensin Ⅱ（Ang-Ⅱ），soluble suppressor of tumorigenicity factor（sST2），N-terminal B-type natriuretic peptide precursor（NT-proBNP），and glucose regulated protein 78（GRP78） content in the serum of each group of rats. Flow cytometry was used to detect the levels of reactive oxygen species（ROS） in myocardial tissue. HE staining was used to observe the morphological changes of myocardial cells in each group of rats. Masson staining was used to observe the structural changes of myocardial collagen tissue. And the collagen volume fraction（CVF） was calculated. Western blot was used to detect the expression of IRE1，XBP1，and GRP78 related proteins in the myocardial tissue of each group of rats. [Results] Compared with the Sham group，the HWI in the Model rats increased significantly（P＜0.05）；the systolic and diastolic blood pressure，LVEF，LVFS，LVESD，LVEDD，Ang-Ⅱ，sST2，NT pro BNP，GRP78，and ROS levels in the Model rats increased significantly（P＜0.05）；HE staining shows disordered arrangement of myocardial cells with infiltration of inflammatory cells，while Masson staining shows pathological changes such as irregular arrangement of myocardial cells，fibrous tissue proliferation，and abundant expression of blue collagen tissue，with increased CVF. The protein levels of P-IRE1/IRE1，XBP1，and GRP78 in myocardial tissue were elevated，and the differences were statistically significant（P＜0.05）. Compared with the model group，HWI decreased in the QS-H group and 4-PBA group（P＜0.05）；the 4-PBA group showed a decrease in systolic and diastolic blood pressure；the levels of LVEF，LVFS，LVESD，LVEDD，serum Ang-Ⅱ，sST2，NT-pro BNP，ROS，and GRP78 decreased in the QS-H group and 4-PBA group（P＜0.05），and the protein expression of P-IRE1/IRE1，XBP1，and GRP78 in myocardial tissue decreased，with statistical differences（P＜0.05）. [Conclusion] Qishen Yiqi Dripping Pills can alleviate myocardial tissue damage，reduce oxidative stress and endoplasmic reticulum stress levels，which may be related to the inhibition of the IRE1/XBP1 signaling pathway. |
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