Eur Rev Med Pharmacol Sci 2020; 24 (9): 5118-5126

DOI: 10.26355/eurrev_202005_21205

Effect of atorvastatin on pulmonary hypertension rats through regulating notch signaling pathway

Y.-T. Zhu, H. Liu, X.-Q. Zhang, M.-M. Tang, J.-Y. Liu, G.-Q. Cao

Internal Medicine, Jinan Tianqiao People’s Hospital, Jinan, China. doctorqq@126.com


OBJECTIVE: To study the effect of atorvastatin on pulmonary hypertension (PAH) rats through regulating the Notch signaling pathway.

MATERIALS AND METHODS: The rat model of PAH was established via hypoxic feeding and the Control group (n=10), PAH model group (Model group, n=10) and atorvastatin treatment group (ATO group, n=10) were set up. The right ventricular systolic pressure (RVSP) and right ventricular hypertrophy index (RVHI) in each group were determined, the wet/dry weight (W/D) ratio of lung tissues was determined, and the tumor necrosis factor-α (TNF-α), myeloperoxidase (MPO) and interleukin-6 (IL-6) were detected via enzyme-linked immunosorbent assay (ELISA). Moreover, the pathological changes in lung tissues of rats were detected via hematoxylin-eosin (HE) staining and the apoptosis level was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Finally, the Notch signaling pathway and apoptosis level in tissues were detected via quantitative Polymerase Chain Reaction (qPCR), and the protein expression level of Notch pathway in lung tissues was determined through Western blotting.

RESULTS: Both RVSP and RVHI in Model group were significantly higher than those in Control group and ATO group (p<0.05). In Model group, the levels of inflammatory factors MPO, IL-6, and TNF-α were significantly increased, and the W/D ratio was also significantly increased compared with those in Control group (p<0.05). The results of HE staining showed that the lung tissue injury in Model group was severe (p<0.05). According to the TUNEL staining results, the number of apoptotic cells in lung tissues was markedly larger in Model group than that in ATO group (p<0.05), and the expression levels of Caspase-3 and IL-6 in Model group were remarkably higher than those in ATO group (p<0.05), while the expression level of B-cell lymphoma-2 (Bcl-2) in Model group was remarkably lower than that in ATO group (p<0.05). Besides, the gene and protein expression levels of Notch1 in ATO group were evidently lower than those in Model group (p<0.05), indicating that atorvastatin can effectively suppress the expression of Notch.

CONCLUSIONS: Atorvastatin can inhibit PAH in rats by suppressing the Notch pathway.

Free PDF Download

To cite this article

Y.-T. Zhu, H. Liu, X.-Q. Zhang, M.-M. Tang, J.-Y. Liu, G.-Q. Cao
Effect of atorvastatin on pulmonary hypertension rats through regulating notch signaling pathway

Eur Rev Med Pharmacol Sci
Year: 2020
Vol. 24 - N. 9
Pages: 5118-5126
DOI: 10.26355/eurrev_202005_21205