Improving Effects of Astragalus Polysaccharides on Cardiac Function via Keap1/Nrf2-ARE Signal Pathway in Adjuvant Arthritis Rats

ObjectiveTo observe the effect of Astragalus polysaccharides (APS) on cardiac function and expression of Keap1/Nrf2-ARE signal pathway in adjuvant arthritis (AA) rats.MethodsForty-eight rats were randomly divided into normal control (NC) group, model control (MC) group, leflunomide (LEF) group, and APS group. The AA model rats were induced with Freund's complete adjuvant, then administration began from day 19 after modeling for 30 d. The paw swelling and arthritic index (AI), the cardiac function indexes, the expression of Keap1, maf, Nrf2 mRNAs, and HO-1, r-GCS proteins in cardiac tissues were observed. Oxidation-related substances (SOD, MDA, ROS, and TAC) and cytokines (IL-10 and TNF-α) were also determined.ResultsCompared with NC group, the paw swelling and AI were increased, and the body weight was decreased in MC group. HR, HI, LVSP, LVEDP, and levels of MDA, TAC, ROS, RNS, and TNF-α in MC group were increased, while dp/dtmax and levels of GSH, TRX, and IL-10 were decreased. Compared with MC group, LEF group showed higher HR and ± dp/dtmax, and lower LVEDP. In APS group, the HR, LVSP, and LVEDP were decreased and ±dp/dtmax was increased. TNF-α was decreased, TAC, ROS, MDA, and IL-10 were increased in both LEF and APS groups. APS and LEF groups also showed less MDA, TAC, ROS, and SOD, and the differences were statistically significant. Spearman correlation analysis showed that the cardiac function parameters were positively correlated with Keap1, anti-oxidant indicators, and anti-inflammation cytokines, and negatively correlated with Nrf2, oxidation indictors, pro-inflammation cytokines, and inflammation indictors.ConclusionAPS can adjust the expression of Keap1/Nrf2-ARE signal pathway in AA rats, and can also improve their cardiac function. The mechanism may be involved in increasing myocardial anti-oxidant capacity, reducing oxidative stress, and inhibiting inflammation.