Effect of Triptolide on Cardiac Function in Arthritic Rats and Its Mechanism

WAN Lei, LIU Jian, HUANG Chuan-bing, SUN Yue, ZHANG Xiao-jun, LIU Tian-yang

Abstract

To observe the changes of cardiac function in arthritic rats and the effect of triptolide on it.  Methods  Forty rats were divided in random into normal control (NC) group, model control (MC) group, leflunomide (LEF) group and triptolide (TP) group. Except for the normal group, rats in the other three groups were injected with Freund's complete adjuvant to create arthritic inflammation in the right hind paws, and the interventional drug was administered on the 12th day after the inflammation. By treating for 30 d, the cardiac function of rats was detected by left ventricular catheterization. The expressions of superoxide dismutase (SOD), malondialdehyde (MDA), reacitve oxygen species (ROS), total antioxidation (T-AOC), interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α) in serum were measured by enzyme-linked immunosorbent assay. The expressions of keap-like protein 1 (Keap1), muscular aponeurotic fibrosarcom (maf) and nuclear factor-E2 related factor2 (Nrf2) mRNAs in cardiac tissue were detected by real-time PCR. The expressions of Keap1, maf and Nrf2 proteins in heart tissues were detected by Western blot.  Results  Comparing with the normal group, the heart rate (HR), heart index (HI), left ventricular systolic pressure (LVSP), and left ventricular end-diastolic pressure (LVEDP) of the model group were significantly increased, whereas the maximum change rate of ventricular pressure rise or decline (±dp/dtmax) was significantly decreased (P<0.01). SOD, MDA, ROS, T-AOC, and TNF-α were all increased, and IL-10 was significantly decreased (P<0.01). The mRNA and protein expressions of Keap1, maf and Nrf2 in heart tissues were increased (P<0.01). Comparing with the model group, HR, HI, LVSP, and LVEDP in the triptolide group were significantly decreased, whereas the ±dp/dtmax was significantly increased (P<0.01). SOD, MDA, T-AOC, ROS, TNF-α decreased while the IL-10 increased (P<0.05, P<0.01). The expressions of Keap1, maf and Nrf2 mRNAs and proteins in the heart tissues of the triptolide group were decreased (P<0.01).   Conclusion  Triptolide could improve cardiac function in arthritic rats, and the mechanism may related to its ability of improving the anti-oxidationin cardiomyocytes, reducing oxidative stress damage, and inhibiting abnormal immune inflammatory response.

 

Keywords: Adjuvant arthritis, Cardiac function, Oxidative stress, Triptolide

 

Full Text:

PDF


References


PEÇANHA T， RODRIGUES R， PINTO A J， et al. Chronotropic incompetence and reduced heart rate recovery in rheumatoid arthritis. J Clin Rheumatol，2018，24(7): 375–380.

ZIMMERMANN M， VODICKA E， HOLMAN A J， et al. Heart rate variability testing: could it change spending for rheumatoid arthritis patients in the United States? An exploratory economic analysis J Med Econ，2018，21(7): 712–720.

DUDEK M， KAŁUŻNA-OLEKSY M， MIGAJ J， et al. Difficult diagnosis of heart failure in rheumatoid arthritis: six-year follow-up of constrictive pericarditis.Kardiol Pol， 2018， 76(3): 675[2019-05-06]. https://doi.org/10.5603/KP.2018.0066.

PHULL A R， NASIR B， HAQ I U， et al. Oxidative stress, consequences and ROS mediated cellular signaling in rheumatoid arthritis. Chem Biol Interact，2018，281: 121–136.

BALA A， MONDAL C， HALDAR P K， et al. Oxidative stress in inflammatory cells of patient with rheumatoid arthritis: clinical efficacy of dietary antioxidants. Inflammopharmacology，2017，25(6): 595–607.

CHU J， WANG X， BI H， et al. Dihydromyricetin relieves rheumatoid arthritis symptoms and suppresses expression of pro-inflammatory cytokines via the activation of Nrf2 pathway in rheumatoid arthritis model. Int Immunopharmacol，2018，59: 174–180.

LOBODA A， DAMULEWICZ M， PYZA E， et al. Role of Nrf2/HO-1 system in development, oxidative stress response and diseases: an evolutionarily conserved mechanism. Cell Mol Life Sci，2016，73(17): 3221–3247.

WANG S， ZUO S， LIU Z， et al. Study on the efficacy and mechanism of triptolide on treating TNF transgenic mice with rheumatoid arthritis. Biomed Pharmacother，2018，106: 813–820.

FAN D， HE X， BIAN Y， et al. Triptolide modulates TREM-1 signal pathway to inhibit the inflammatory response in rheumatoid arthritis. Int J Mol Sci， 2016， 17(4): 498[2019-05-06]. https://doi.org/10.3390/ijms17040498.

LIANG Z， LEO S， WEN H， et al.Triptolide improves systolic function and myocardial energy metabolism of diabetic cardiomyopathy in streptozotocin-induced diabetic rats. BMC Cardiovasc Disord， 2015， 15: 42[2019-05-06]. https://doi.org/10.1186/s12872-015-0030-4.

OGDIE A， YU Y， HAYNES K， et al. Risk of major cardiovascular events in patients with psoriatic arthritis, psoriasis and rheumatoid arthritis: a population-based cohort study. Ann Rheum Dis，2015，74(2): 326–332.

SINNATHURAI P， CAPON A， BUCHBINDER R， et al. Cardiovascular risk management in rheumatoid and psoriatic arthritis: online survey results from a national cohort study. BMC Rheumatol， 2018， 2: 25[2019-05-06]. https://doi.org/10.1186/s41927-018-0032-9.

AVINA-ZUBIETA J A， CHOI H K， SADATSAFAVI M， et al. Risk of cardiovascular mortality in patients with rheumatoid arthritis: a meta-analysis of observational studies. Arthritis Rheum，2008，59(12): 1690–1697.

SOLOMON D H， KREMER J， CURTIS J R， et al. Explaining the cardiovascular risk associated with rheumatoid arthritis: traditional risk factors versus markers of rheumatoid arthritis severity. Ann Rheum Dis， 2010，69(11): 1920–1925.

THIMMULAPPA R K， LEE H， RANGASAMY T， et a1. Nrf2 is a critical regulator of the innate immune response and survival during experimental sepsi. J Clin Invest，2006，116(4): 984–995.

LIANG N， KITTS D D. Amelioration of oxidative stress in Caco-2 cells treated with pro-inflammatory proteins by chlorogenic acid isomers via activation of the Nrf2-Keap1-ARE-Signaling pathway. J Agric Food Chem，2018，66(42): 11008–11017.

YAZICI D， TOKAV S， AVDIN S， et al. Echocardiographic evaluation of cardiac diastolic function in patients with rheumatci d arthritis: 5 years of follow-up. Clin Rheumatol，2008，27: 647–650.

YU H， SHI L， ZHAO S， et al. Triptolide attenuates myocardial ischemia/reperfusion injuries in rats by inducing the activation of Nrf2/HO-1 defense pathway. Cardiovasc Toxicol，2016，16(4): 325–335.

HOU Z， CHEN L， FANG P， et al. Mechanisms of triptolide-induced hepatotoxicity and protective effect of combined use of isoliquiritigenin: possible roles of Nrf2 and hepatic transporters.Front Pharmacol， 2018， 9: 226[2019-05-06]. https://doi.org/10.3389/fphar.2018.00226.

YAND Y Q， YAN X T， WANG K， et al. Triptriolid e alleviates lipopolysaccharide-induced liver injury by Nrf2 and NF-κB signaling pathways.Front Pharmacol， 2018， 9: 999[2019-05-06]. https:/doi.org/ 10.3389/fphar.2018.00999.

WU B K， YUAN R Y， CHANG Y P， et al. Epicatechin isolated from Tripterygium wilfordii extract reduces tau-GFP-induced neurotoxicity in zebrafish embryo through the activation of Nrf2. Biochem Biophys Res Commun，2016，477(2): 283–289.


Refbacks

  • There are currently no refbacks.