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南葶苈子油脂纳米粒通过 PLC/IP3R/Ca 信号通路改善野百合碱诱导的大鼠肺动脉高压。

Fatty Oil of Descurainia Sophia Nanoparticles Improve Monocrotaline-Induced Pulmonary Hypertension in Rats Through PLC/IP3R/Ca Signaling Pathway.

机构信息

College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, 450008, People's Republic of China.

The Engineering and Technology Center for Chinese Medicine Development of Henan Province, Zhengzhou, 450046, People's Republic of China.

出版信息

Int J Nanomedicine. 2023 Dec 8;18:7483-7503. doi: 10.2147/IJN.S436866. eCollection 2023.

Abstract

PURPOSE

Fatty oil of (OIL) has poor stability and low solubility, which limits its pharmacological effects. We hypothesized that fatty oil nanoparticles (OIL-NPs) could overcome this limitation. The protective effect of OIL-NPs against monocrotaline-induced lung injury in rats was studied.

METHODS

We prepared OIL-NPs by wrapping fatty oil with polylactic-polyglycolide nanoparticles (PLGA-NPs) and conducted in vivo and in vitro experiments to explore its anti-pulmonary hypertension (PH) effect. In vitro, we induced malignant proliferation of pulmonary artery smooth muscle cells (RPASMC) using anoxic chambers, and studied the effects of OIL-NPs on the malignant proliferation of RPASMC cells and phospholipase C (PLC)/inositol triphosphate receptor (IP3R)/Ca signal pathways. In vivo, we used small animal echocardiography, flow cytometry, immunohistochemistry, western blotting (WB), polymerase chain reaction (PCR) and metabolomics to explore the effects of OIL-NPs on the heart and lung pathological damage and PLC/IP3R/Ca signal pathway of pulmonary hypertension rats.

RESULTS

We prepared fatty into OIL-NPs. In vitro, OIL-NPs could improve the mitochondrial function and inhibit the malignant proliferation of RPASMC cells by inhibiting the PLC/IP3R/Casignal pathway. In vivo, OIL-NPs could reduce the pulmonary artery pressure of rats and alleviate the pathological injury and inflammatory reaction of heart and lung by inhibiting the PLC/IP3R/Ca signal pathway.

CONCLUSION

OIL-NPs have anti-pulmonary hypertension effect, and the mechanism may be related to the inhibition of PLC/IP3R/Casignal pathway.

摘要

目的

(油)的脂肪油稳定性差,溶解度低,限制了其药理作用。我们假设脂肪油纳米粒(OIL-NPs)可以克服这一限制。本研究旨在探讨 OIL-NPs 对野百合碱诱导的大鼠肺损伤的保护作用。

方法

我们通过将脂肪油包裹在聚乳酸-聚乙二醇纳米粒(PLGA-NPs)中来制备 OIL-NPs,并进行了体内和体外实验来探索其抗肺动脉高压(PH)的作用。在体外,我们使用缺氧室诱导肺动脉平滑肌细胞(RPASMC)恶性增殖,并研究了 OIL-NPs 对 RPASMC 细胞恶性增殖和磷脂酶 C(PLC)/三磷酸肌醇受体(IP3R)/Ca 信号通路的影响。在体内,我们使用小动物超声心动图、流式细胞术、免疫组织化学、蛋白质印迹(WB)、聚合酶链反应(PCR)和代谢组学来探讨 OIL-NPs 对肺动脉高压大鼠心脏和肺组织病理损伤及 PLC/IP3R/Ca 信号通路的影响。

结果

我们将脂肪油制成 OIL-NPs。体外实验表明,OIL-NPs 可以通过抑制 PLC/IP3R/Ca 信号通路改善线粒体功能,抑制 RPASMC 细胞的恶性增殖。在体内,OIL-NPs 可以降低大鼠肺动脉压,通过抑制 PLC/IP3R/Ca 信号通路减轻心肺组织的病理损伤和炎症反应。

结论

OIL-NPs 具有抗肺动脉高压作用,其机制可能与抑制 PLC/IP3R/Ca 信号通路有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8710/10714987/f6eb18a54697/IJN-18-7483-g0001.jpg

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