Treg Immunomodulation Contributes to the Anti-atherosclerotic Effects of Huxin Formula in ApoE -/- Mice.

Autor: Ou XM; The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, 510405, China.; Department of Cardiology, Guangdong Provincial Hospital of Chinese Medicine, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510020, China., Cai J; The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, 510405, China.; Department of Cardiology, Guangdong Provincial Hospital of Chinese Medicine, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510020, China., Hu XY; The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, 510405, China.; Department of Cardiology, Guangdong Provincial Hospital of Chinese Medicine, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510020, China., Zeng QH; Department of Cardiology, Guangdong Provincial Hospital of Chinese Medicine, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510020, China., Lan TH; Department of Cardiology, Guangdong Provincial Hospital of Chinese Medicine, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510020, China.; Guangdong Provincial Key Laboratory of Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases, Guangzhou, 510020, China., Jiang W; Department of Cardiology, Guangdong Provincial Hospital of Chinese Medicine, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510020, China. jiangwei@gzucm.edu.cn.; Guangdong Provincial Key Laboratory of Chinese Medicine for Prevention and Treatment of Refractory Chronic Diseases, Guangzhou, 510020, China. jiangwei@gzucm.edu.cn.
Jazyk: angličtina
Zdroj: Chinese journal of integrative medicine [Chin J Integr Med] 2024 Oct; Vol. 30 (10), pp. 896-905. Date of Electronic Publication: 2024 May 16.
DOI: 10.1007/s11655-024-3663-2
Abstrakt: Objective: To explore the effects of Huxin formula (HXF) in curtailing atherosclerosis and its underlying mechanism.
Methods: According to random number table method, 24 specific pathogen free male ApoE -/- mice were randomly divided into model group, HXF low-dose (HXF-L) group (8.4 g/kg daily), HXF high-dose (HXF-H) group (16.8 g/kg daily), and pravastatin (8 mg/kg daily) group in Experiment I (n=6 per group). C57BL/6J mice served as the control group (n=6). ApoE -/- mice in HXF-L, HXF-H, pravastatin groups were fed a Western diet and administered continuously by gavage for 12 weeks, while C57BL/6J mice in the control group were fed conventional lab mouse chow for 12 weeks. Further, Tregs were depleted by weekly intraperitoneal injection of purified anti-mouse CD25 antibody (PC61, 250 µg per mouse) for 4 weeks in Experiment II (n=6 per group). Oil Red O and Masson staining were used to evaluate the plaque area and aortic root fibrosis. The CD4 + CD25 + Foxp3 + Treg counts in the lymph nodes and spleen cells were detected using flow cytometric analysis. The transforming growth factor-β1 (TGF-β1), interleukin (IL)-10, and IL-6 serum levels were examined by MILLIPLEX® MAP technology. Quantitative real-time reverse transcription PCR (qRT-PCR) and Western blot were utilized to assess the expression of TGF-β mRNA and protein in the aorta. The expression of CD4 + T lymphocytes, macrophages and smooth muscle cells in the aortic root were detected by immunofluorescence staining.
Results: HXF reduced plaque area in ApoE -/- mice (P<0.01). HXF increased the Treg counts in the lymph nodes and spleen cells (P<0.05 or P<0.01). Moreover, HXF alleviated inflammatory response via elevating IL-10 and TGF-β 1 serum levels (P<0.05), while decreasing the IL-6 serum levels in ApoE -/- mice (P>0.05). Also, HXF upregulated the expression of TGF-β mRNA and protein in the aorta (P<0.05). Additionally, HXF attenuated CD4 + T lymphocytes, macrophages and smooth muscle cells in aortic root plaque (P<0.01). Furthermore, the depletion of Tregs with CD25 antibody (PC61) curtailed the reduction in plaque area and aortic root fibrosis by HXF (P<0.01).
Conclusion: HXF relieved atherosclerosis, probably by restraining inflammatory response, reducing inflammatory cell infiltration and attenuating aortic root fibrosis by increasing Treg counts.
(© 2024. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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