Abstract：Objective: To investigate the effect of pachymic acid (PA) on endothelial cell damage in essential hypertension (EHT) rats by regulating the interleukin-6 (IL-6)/tyrosine kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway. Methods: Sixty EHT rats were randomly separated into EHT group, low, high concentration PA group, benazepril group, high concentration PA+rrIL-6 group, with 12 rats in each group. Additional 12 Wistar-Kyoto (WKY) rats were selected as the control group. The changes in diastolic blood pressure (DBP), systolic blood pressure (SBP), and mean arterial pressure (MAP) of rats were detected. Enzyme-linked immunosorbent assay (ELISA) was applied to detect levels of endothelin-1 (ET-1), intercellular adhesion molecule-1 (ICAM-1), and von Willebrand factor (vWF) in serum. The hematoxylin and eosin (H&E) staining was applied to detect the pathology of the thoracic aorta. Rat umbilical vein endothelial cells (UVECs) were separated into Vitro-control group, Vitro-EHT group, Vitro-low concentration PA group, Vitro-high concentration PA group, Vitro-Benazepril group, and Vitro-high concentration PA+rrIL-6 group. ELISA was applied to detect the levels of tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), and IL-1β in the supernatant of UVECs. Flow cytometry was applied to detect UVECs apoptosis. Western blot was applied to detect the proteins levels of IL-6, p-STAT3, and p-JAK2 in UVECs. Results: Compared with the control group, the endometrial structure of the thoracic aorta in the EHT group was abnormal, with defects or protrusions, and the boundary between the endometrium and outer membrane was blurred, the levels of DBP, SBP, MAP, and serum ET-1, ICAM-1, and vWF were significantly increased (P<0.05). Compared with the EHT group, the pathological damage of the thoracic aorta in rats in the low, high concentration PA, and benazepril group was significantly improved, the levels of DBP, SBP, MAP, and serum ET-1, ICAM-1, and vWF were significantly decreased (P<0.05). Compared with the Vitro-control group, the levels of TNF-α, IL-1β in the supernatant, the apoptosis rate of UVECs, and the proteins levels of IL-6, p-STAT3, and p-JAK2 in UVECs in the Vitro-EHT group were significantly increased, while the level of IL-10 was significantly decreased (P<0.05). Compared with the Vitro-EHT group, the levels of TNF-α, IL-1β in the supernatant, apoptosis rate of UVECs, and IL-6, p-STAT3, and p-JAK2 proteins in UVECs in the Vitro-low concentration PA group, the Vitro-high concentration PA group, and the Vitro-Benazepril group were significantly decreased, while the level of IL-10 was significantly increased (P<0.05). RrIL-6 reversed the inhibitory effects of high concentrations PA on endothelial injury, Ang Ⅱ induced UVECs inflammation and inhibited apoptosis in EHT rats. Conclusion: PA may inhibit endothelial cell damage in EHT rats by inhibiting the IL-6/JAK2/STAT3 pathway.
[1] Wang R,Guo Y,Li L,et al.Role of thioredoxin-interacting protein in mediating endothelial dysfunction in hypertension[J].Genes Dis,2020,9(3):753-765. [2] 刘云宽,高敏,林柳任,等.基于网络药理学的六味地黄丸治疗高血压作用机制探讨[J].中国现代中药,2021,23(7):1221-1229. [3] Alanazi AZ,Clark MA.Angiotensin Ⅲ induces JAK2/STAT3 leading to IL-6 production in rat vascular smooth muscle cells[J].Int Mol Sci,2019,20(22):5551-5566. [4] 王丹,王瑶瑶,瞿金念,等.MiR-211-5p在原发性高血压患者血清中的表达及对血管内皮细胞凋亡和炎性反应的影响[J].中国循证心血管医学杂志,2022,14(12):1476-1480. [5] 苗树船,夏勋,张列.茯苓酸抑制H2O2诱导的脑微血管内皮细胞凋亡及促进细胞存活[J].西部医学,2021,33(7):982-986. [6] 刘凤,刘增长.茯苓酸通过激活Nrf2/HO-1信号通路改善OX-LDL诱导的人脐静脉内皮细胞损伤[J].中国免疫学杂志,2020,36(2):164-168,179. [7] Ren Y,Xie W,Yang S,et al.Angiotensin-converting enzyme 2 inhibits inflammation and apoptosis in high glucose-stimulated microvascular endothelial cell damage by regulating the JAK2/STAT3 signaling pathway[J].Bioengineered,2022,13(4):10802-10810. [8] Luo JY,Fu D,Wu YQ,et al.Inhibition of the JAK2/STAT3/SOSC1 signaling pathway improves secretion function of vascular endothelial cells in a rat model of pregnancy-induced hypertension[J].Cell Physiol Biochem,2016,40(3-4):527-537. [9] Duan B,Li Y,Geng H,et al.Naringenin prevents pregnancy-induced hypertension via suppression of JAK/STAT3 signalling pathway in mice[J].Int Clin Pract,2021,75(10):14509.
2024, Vol. 30 
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