Mechanism of capsaicin in CIA rats based on AKT-HK2-NF-κB signaling pathway
Objective To explore the role of capsaicin(CAP)on the protein-serine-threonine kinase(Akt)/hexokinase 2(HK2)/nuclear factor kappa-B(NF-κB)signaling pathway in rats with rheumatoid arthritis(RA)and its mechanism.Methods Emulsion of bovine type Ⅱ collagen with complete Freund's adjuvant(CFA)was subcutaneously inject into the tail roots of SD rats to construct a collagen-induced arthritis(CIA)rat model as model group.An equal volume of physiological saline was injected into rat tail roots in blank group.The successfully modeled SD rats were randomly divided into low-dose CAP group(1 mg/kg),medium-dose CAP group(2 mg/kg),high-dose CAP group(3 mg/kg)and positive control group(Tripterygium wilfordii,40 mg/kg).At two weeks after successful modeling,blank and model groups were given an equal amount of physiological saline by gavage.The degree of rat foot swelling was measured before modeling,after modeling and during drug administration.After 3 weeks of administration,ankle joints were sectioned and stained with HE.Western blot was used to detect the expression of AKT,HK2,and NF-κB in rat synovial tissues.RT-qPCR was applied to detect the mRNA expressions of AKT,HK2,and NF-κB.ELISA was applied to detect the content of rat serum interleukin-6(IL-6).Results When compared to model group,high-dose CAP group showed a decrease in AI score in right hind feet of the rats(P＜0.05)and a reduction in foot swelling(P＜0.05).There were no statistically significant differences in AI score of the right hind foot and the degree of foot swelling between positive control group and high-dose CAP group(P＞0.05).HE staining revealed that when compared to blank group,rat ankle synovial membrane in model group had significant proliferation,destruction of subchondral bone structure,accompanied by inflammatory cell infiltration and invasion of synovial membrane blood vessels.When compared to model group,the rats in positive control and CAP groups showed varying degrees of inhibition of synovial tissue proliferation after drug intervention,and inflammatory cell infiltration and neovascularization in rat synovial tissues were decreased in high dose-and medium dose-CAP groups.When compared to model group,positive control and high-dose CAP groups showed a decrease in IL-6 levels(P＜0.05).When compared to model group,the mRNA and protein expression levels of AKT,HK2,and NF-κB in synovial tissues were decreased in high dose-and medium dose-CAP groups and positive control group(P＜0.05).Conclusion High dose CAP may alleviate inflammatory response of the ankle joint in rats with RA,and its mechanism may be related to inhibiting AKT-HK2-NF-κB pathway-associated proteins and reducing serum IL-6 level.
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维普
