Compound Tripterygium wilfordii preparation improves joint inflammation in adjuvant arthritis rats via regulating macrophage polarization through regulating Notch1/Jagged1/RBP-Jκ/Hes1 signaling pathway
Objective It is to observe the effects of compound Tripterygium wilfordii preparation on joint inflammation in adjuvant arthritis rats via regulating macrophage polarization through regulating Notch1/Jagged1/RBP-Jκ/Hes1 signaling pathway.Methods Thirty male SD rats were randomly divided into normal group,model group,compound Tripterywilfornia preparation group,methotrexate group,Notch1 inhibitor group,with 6 rats in each group.The rats of all groups except for the normal group were prepared to establish models of adjuvant arthritis(AA).The dosage was administered on the 19th day after inflammation,and the degree of toe swelling and arthritis index of each group were detected 30 days after adminis-tration.Beginning on the 19th day after the onset of inflammation,the compound Tripterywilfornia preparation group was given 340 mg/L of compound Tripterywilfornia preparation suspension by gavage,once per day;the methotrexate group was given 0.95 mg/L of methotrexate suspension by gavage,once per week;the Notch1 inhibitor group was given 0.56 mg/L of Notch1 inhibitor suspension by caudal vein injection,every other day;the normal group and model group were given normal saline by gavage,once per day.All the groups were continuously treated for 30 days.The toe swelling and arthritis index of rats in each group were detected;at the end of the last gavage,the histopathological morphology of synovial joint tissues was observed by HE staining,the serum levels of IL-1β,IL-4,IL-10,IL-13,and TNF-α were detected by ELISA,the expres-sions of inflammation polarization markers CD86 and CD206 in peripheral blood were detected by flow cytometry,and the expressions of Notch1,Jagged1,RBP-Jκ,and Hes1 proteins in synovial joint tissues were detected by immunohistochemis-try and immunoblotting.Results Compared with the normal group,the toe swelling,arthritis index,CD86 percentage in peripheral blood,levels of IL-1β and TNF-α in serum,and relative expressions of Notch1,Jagged1,RBP-Jκ,and Hes1 proteins in synovial tissues of rats in the model group were all significantly increased(all P＜0.05),while CD206 percent-age in peripheral blood and the levels of IL-4,IL-10 and IL-13 in serum were significantly decreased(all P＜0.05).Com-pared with the model group,the toe swelling,arthritis index(except for the Notch 1 inhibitor group),CD86 percentage in peripheral blood,levels of IL-1β and TNF-α in serum,and relative expressions of Notch1,Jagged1,RBP-Jκ,and Hes1 proteins in synovial tissues of rats in the compound Tripterywilfornia preparation group,methotrexate group,Notch1 inhibi-tor group were all significantly decreased(all P＜0.05),while CD206 percentage in peripheral blood and the levels of IL-4,IL-10 and IL-13 in serum were significantly increased(all P＜0.05).Conclusion Compound Tripterygium wilfordii preparation can effectively alleviate joint inflammation in AA rats,and the mechanism may be related to regulate macro-phage polarization and inhibit the secretion of pro-inflammatory cytokines via inhibiting Notch1/Jagged1/RBP-Jκ/Hes1 signaling pathway.
NETL
NSTL
万方数据
