Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an enzyme with several pro-inflammatory properties that involved in the pathogenesis of atherosclerosis but some investigation shows controversial views regarding its biological role. We examined the effect of a selective inhibitor of Lp-PLA2 (darapladib) to the inflammation marker such as nuclear factor kappa B (NF-κB) and interleukin-6 (IL-6) expression in aortic tissue and insulin resistance of type 2 diabetes mellitus (T2DM) rat model. 30 Sprague-dawley rats were randomly divided into the normal group, T2DM group and T2DM with darapladib treatment. Induction of T2DM was done by giving high-fat diet and low dose injection of streptozotocin. Blood glucose level and insulin plasma concentration were measured to calculate insulin resistance in mice. Eight weeks and sixteen weeks after treatment, we compared expression of NF-κB and IL-6 in aortic tissue. Darapladib treatment group exhibited significant reduction of insulin resistance (0.64+0.11 vs 2.07+0.16, p<0.05 at 8 weeks; and 0.93+0.08 vs 6.48+0.55 at 16 weeks) compared with T2DM group. On immunofluorescence analysis, darapladib significantly decreased NF-κB and IL-6 expression at 2 serial treatments. These data suggested that Lp-PLA2 played a role in inflammation process and improve insulin resistance occurring in the metabolic disorder.

Objective: Lipoprotein-associated phospholipase A2 (Lp-PLA 2 ) is an enzyme with several pro-inflammatory properties that involved in pathogenesis of atherosclerosis, but some investigation shows controversial views regarding its biological role. We examined the effect of selective inhibitor of Lp-PLA 2 (darapladib) to the inflammation marker, intima-media thickness (IMT), and insulin resistance (IR) of type 2 diabetes mellitus (T2DM) rat model. This study aimed to measure lysophosphatidylcholine (lyso-PC) in serum and aortic tissue, nuclear factor kappa B (NF-κB) expression, IMT, and IR with darapladib treatment in a T2DM rat model. Methods:30 Sprague-Dawley rats were randomly divided into normal group, T2DM group and T2DM with darapladib treatment. Induction of T2DM was done by giving high-fat diet and low dose injection of streptozotocin. Blood glucose level and insulin plasma concentration were measured to calculate IR. 8 weeks and 16 weeks after treatment, we compared lyso-PC level, NF-κB expression, and IMT.Results: Darapladib significantly decreased lyso-PC level, NF-κB expression, and IMT at two serial treatments. Darapladib treatment group exhibited significant reduction of IR (0.64±0.11 vs. 2.07±0.16, at 8 weeks; and 0.93±0.08 vs. 6.48±0.55 at 16 weeks) compared with T2DM group. Conclusions:These data suggested that Lp-PLA 2 played a role in inflammation process, atherosclerosis, and IR occurring in metabolic disorder.