[Effect of moxibustion on SIRT1/eNOS signaling pathway in ApoE-/- atherosclerotic mice].

Objectives: To observe the effect of moxibustion on pathological structure and ultrastructural changes of thoracic aorta, the expression of silent information regulator 1 (SIRT1) and endothelial nitric oxide synthase (eNOS) in ApoE^-/- atherosclerosis (AS) mice, so as to explore its possible mechanism in preventing and treating AS.

Methods: Ten C57BL/6J mice were fed a normal diet as the control group, and 30 ApoE^-/- mice were fed a high-fat diet to establish the AS model, which were randomly divided into the model group, moxibustion group, and moxibustion+EX527 group, with 10 mice in each group. Mice in the moxibustion group received mild moxibustion treatment at "Danzhong"(CV17), "Shenque"(CV8), "Neiguan"(PC6, bilateral), and "Xuehai" (SP10, bilateral) for 30 min, the mice in the moxibustion+EX527 group were given intraperitoneal injection of EX527 (10 mg/kg) 30 min before moxibustion, with both treatments given once daily, 5 times a week, with a total intervention period of 12 weeks. After the intervention, the contents of nitric oxide (NO) and endothelin-1 (ET-1) in serum were detected by ELISA. HE staining and transmission electron microscopy (TEM) were used to observe the pathological structure and ultrastructural changes of thoracic aorta. The expression of endomucin of thoracic aorta was observed by immunofluorescence staining. The protein and mRNA expression levels of SIRT1 and eNOS in thoracic aorta were detected by Western blot and real-time fluorescence quantitative PCR, respectively.

Results: Compared with the control group, the content of serum NO was decreased (P<0.05), while the content of serum ET-1 was increased (P<0.05);the fluorescence intensity of endomucin, the protein and mRNA expression of SIRT1 and eNOS in thoracic aorta were significantly decreased (P<0.05) in the model group. Compared with the model and moxibustion+EX527 groups, the moxibustion group showed a significantly increase in the serum NO contents (P<0.05), and decrease in serum ET-1 contents (P<0.05), and the endomucin fluorescence intensity, SIRT1 and eNOS protein and mRNA were significantly increased (P<0.05). Morphological observation revealed that in the model group, light microscope showed incomplete thoracic aorta structure, uneven inner wall, endothelial cell degeneration and swelling, and TEM showed a few swollen mitochondria and autophagy, and a large number of dilated rough endoplasmic reticulum, and these situations were obviously milder in the moxibustion group.

Conclusions: Moxibustion can reduce vascular endothelial injury, improve endothelial function and promote endothelial repair in AS mice, which may be related to its function in regulating the SIRT1/eNOS signaling pathway.