Abstract:
Objective To investigate the mechanism of argon-helium cryotherapy in regulating the tyrosine-protein kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway, thereby inhibiting the inflammatory response in rats with atherosclerotic occlusive disease (ASO) of the lower extremities.
Methods Forty rats were randomly divided into sham group, lower extremity ASO group, Ar-He Cryo group and Ar-He Cryo+p-JAK group, with 10 rats in each group. The average blood flow velocity of the lower extremity artery, lipid profile and inflammation levels were measured in each group. Hematoxylin-eosin (HE) staining was used to examine histopathological changes in arterial vessel tissues. Western blotting was performed to detect the expression levels of JAK2, p-JAK2, STAT3, p-STAT3 and suppressor of cytokine signaling 3 (SOCS3) proteins in arterial vessel tissues.
Results The average blood flow velocity of the lower extremity artery in the lower extremity ASO group was significantly lower than that in the sham group (P < 0.05). The average blood flow velocity in the Ar-He Cryo group was significantly higher than that in the ASO group (P < 0.05). The average blood flow velocity in the Ar-He Cryo+p-JAK group was significantly lower than that in the Ar-He Cryo group (P < 0.05). Serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) levels, tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) levels and endothelin-1 (ET-1) content in the lower extremity ASO group were significantly higher than those in the sham group, while serum high-density lipoprotein cholesterol (HDL-C) levels and nitric oxide (NO) content were significantly lower than those in the sham group (P < 0.05). In the Ar-He Cryo group, serum TC, TG, LDL-C levels as well as TNF-α, IL-1β, IL-6 levels and ET-1 content were significantly lower than those in the lower extremity ASO group, while serum HDL-C levels and NO content were significantly higher (P < 0.05). In the Ar-He Cryo+p-JAK group, serum TC, TG, LDL-C levels as well as TNF-α, IL-1β, IL-6 levels and ET-1 content were significantly higher than those in the Ar-He Cryo group, while HDL-C levels and NO content were significantly lower (P < 0.05). Compared with the sham group, the lower extremity venous vessels in the lower extremity ASO group showed significant stenosis; compared with the lower extremity ASO group, the degree of stenosis in the lower extremity venous vessels was significantly reduced in the Ar-He Cryo group; the degree of stenosis in the lower extremity venous vessels in the Ar-He Cryo+p-JAK group was similar to that in the lower extremity ASO group and significantly more severe than that in the Ar-He Cryo group. The ratios of p-JAK2/JAK2 and p-STAT3/STAT3 in arterial vessel tissues of the lower extremity ASO group were significantly higher than those in the sham group, and SOCS3 protein expression was significantly lower than that in the sham group (P < 0.05). In the Ar-He Cryo group, p-JAK2/JAK2 and p-STAT3/STAT3 in arterial vessel tissues were significantly lower than those in the lower extremity ASO group, and SOCS3 protein expression was significantly higher than that in the lower extremity ASO group (P < 0.05). In the Ar-He Cryo+p-JAK group, p-JAK2/JAK2 and p-STAT3/STAT3 in arterial vessel tissues were significantly higher than those in the Ar-He Cryo group, and SOCS3 protein expression was significantly lower than that in the Ar-He Cryo group (P < 0.05).
Conclusion Argon-helium cryotherapy can reduce lipid deposition in the arteries of rats with lower extremity ASO, inhibit inflammatory responses, and its mechanism may be related to the inhibition of activation of JAK2/STAT3 signaling pathway.