Exploring effect of cyclooxygenase-2 inhibitor on serum lipid profiles in collagen-induced arthritis model using shotgun lipidomics

doi:10.3724/SP.J.1123.2016.03043

Abstract

Abstract:

Rheumatoid arthritis (RA) is an inflammatory disease leading to joint swollen, pain and even deformity. Cardiovascular disease (CVD) is regarded as a major cause of morbidity in patients. Chronic systemic inflammation in patients is an independent CVD risk factor. Cyclooxygenase-2 (COX-2) inhibitor, a commonly used drug in the treatment of RA, can increase the risk of CVD. Lipid metabolic disorder is highly correlated with the occurrence of CVD, thus we investigated the serum lipid changes caused by RA and drug treatment to help to elucidate the mechanism of CVD in RA. Collagen-induced arthritis (CIA) is employed as a model of RA. After modeling, COX-2 inhibitor-meloxicam was orally administrated for three weeks, and the serum lipid profiles were analyzed by the multi-dimensional mass spectrometry-based shotgun lipidomics (MDMS-SL). Totally 105 lipids were detected in serum, including 35 phosphatidylcholines (PCs), 18 lysophosphatidylcholines (LysoPCs), 15 phosphatidyl inositols (PIs), 3 phosphatidyl glycerols (PGs), 19 sphingomyelins (SMs) and 15 ceramides (Cers). In the principle component analysis, it was observed that the lipid profiles of CIA model rats were very different from those of the control rats, and the COX-2 inhibitor can improve the lipid metabolism partly. Further, ANOVA analysis revealed that 39 of the 105 identified lipids were up-regulated in CIA rats, including 7 PIs, 15 SMs, 5 Cers, 10 PCs and 2 LysoPCs. Most of these lipids were down-regulated under the treatment of COX-2 inhibitor. In addition, the five PCs and one LysoPC were abnormally regulated by the drug. The MDMS-SL discovered lipid disturbance in CIA model rats that might be related to risk factors of atherosclerosis; the COX-2 inhibitor can greatly repair the lipid disorder caused by modeling, while induce abnormal changes of some PCs and LysoPC which may cause side-effect.

Key words: collagen-induced arthritis, cyclooxygenase-2 (COX-2) inhibitor, lipid metabolism, multi-dimensional mass spectrometry-based shotgun lipidomics (MDMS-SL), rheumatoid arthritis

CLC Number:

O658

PAN Jieli, HU Changfeng, WEI Shuangshuang, CHEN Jiao, ZHOU Jia. Exploring effect of cyclooxygenase-2 inhibitor on serum lipid profiles in collagen-induced arthritis model using shotgun lipidomics[J]. Chinese Journal of Chromatography, 2016, 34(6): 550-557.

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