Objective: To compare oxidized low density lipoprotein(ox LDL) levels in serum and vascular wall of Sprague-Dawley rats, identify their patterns in 8 weeks and 16 weeks of dyslipidemia induced by high fat diet, compar...Objective: To compare oxidized low density lipoprotein(ox LDL) levels in serum and vascular wall of Sprague-Dawley rats, identify their patterns in 8 weeks and 16 weeks of dyslipidemia induced by high fat diet, compare foam cells in aorta of each group and investigate lipoprotein-associated phospholipase A_2(Lp-PLA_2) role in atherosclerosis by darapladib administration.Methods: This study generated in twenty-four Sprague-Dawley rats. Rats were divided into 6 groups, which were received normal diet(normal group), high fat diet and high fat diet plus darapladib therapy for both 8 weeks and 16 weeks. Surgeries were performed at Week 8 and Week 16 to take the blood serum and aortic tissue. Level of ox LDL in serum,ox LDL aortic tissue, foam cell amount in aortic tissue, and Lp-PLA_2 expression in aortic tissue were measured.Results: There were significant differences in ox LDL level in serum, aortic tissue and foam cell amount(P < 0.05). There was no significant difference in Lp-PLA_2 expression in aortic tissue. Ox LDL in serum and aortic tissue had a very strong correlation(r2> 0.9, P < 0.05).This study also composed an equation for ox LDL level in aortic tissue prediction. Factorial ANOVA found that there was a significant difference of ox LDL level in the interactions between duration and location, location and treatment, and also duration, location and treatment(P < 0.01). Administration of darapladib was able to reduce levels of ox LDL in serum,aortic tissue and foam cell significantly(P < 0.05, P < 0.05 and P < 0.01, subsequently).Conclusions: Ox LDL level is location-dependent and duration-dependent. As a feasible early diagnosis, we can predict ox LDL level in aortic tissue by its level in serum. Though Lp-PLA_2 expression was unsignificant, Lp-PLA_2 inhibition by darapladib can reduce oxidative stress and inflammation in atherogenesis.展开更多
The eicosanoid signaling pathway mediates insect immune reactions to a wide range of stimuli. This pathway begins with the biosynthesis of arachidonic acid (AA) from the hydrolysis of phospholipids catalyzed by phosph...The eicosanoid signaling pathway mediates insect immune reactions to a wide range of stimuli. This pathway begins with the biosynthesis of arachidonic acid (AA) from the hydrolysis of phospholipids catalyzed by phospholipase A_(2) (PLA_(2)). We report here that the PLA_(2) inhibitor, dexamethasone (DEX), impaired the innate immune response including nodulation, encapsulation, and melanization in Ostrinia furnacalis larvae, while AA partially reversed these effects of DEX. We cloned a full-length complementary DNA encoding a PLA_(2), designated as OfsPLA_(2), from O. furnacalis. The open reading frame of OfsPLA_(2) encodes a 195-amino acid residue protein with a 22-residue signal peptide. Sequence alignment analyses indicated that O. furnacalis PLA_(2) might be a Group III secretory PLA_(2). The highest transcript levels of OfsPLA_(2) were detected in the fat body, and its transcript levels increased dramatically after infection with Escherichia coli, Micrococcus luteus, or Beauveria bassiana. Recombinant OfsPLA_(2) significantly induced prophenoloxidase (PPO) activation in larval hemolymph in the presence of Ca^(2+) and encapsulation of agarose beads. Injection of recombinant OfsPLA_(2) into larvae resulted in increased transcript levels of attacin, defencin, and moricin-3 genes. Our results demonstrate the involvement of the eicosanoid signaling pathway in the innate immune response of O. furnacalis larvae and provide new information about the roles of O. furnacalis secretory PLA_(2) in activating PPO and antimicrobial peptide production.展开更多
基金Supported by Indonesia Ministry of Research,Technology,and Higher Education with grant No.530.2/UN10.21/PG/2015
文摘Objective: To compare oxidized low density lipoprotein(ox LDL) levels in serum and vascular wall of Sprague-Dawley rats, identify their patterns in 8 weeks and 16 weeks of dyslipidemia induced by high fat diet, compare foam cells in aorta of each group and investigate lipoprotein-associated phospholipase A_2(Lp-PLA_2) role in atherosclerosis by darapladib administration.Methods: This study generated in twenty-four Sprague-Dawley rats. Rats were divided into 6 groups, which were received normal diet(normal group), high fat diet and high fat diet plus darapladib therapy for both 8 weeks and 16 weeks. Surgeries were performed at Week 8 and Week 16 to take the blood serum and aortic tissue. Level of ox LDL in serum,ox LDL aortic tissue, foam cell amount in aortic tissue, and Lp-PLA_2 expression in aortic tissue were measured.Results: There were significant differences in ox LDL level in serum, aortic tissue and foam cell amount(P < 0.05). There was no significant difference in Lp-PLA_2 expression in aortic tissue. Ox LDL in serum and aortic tissue had a very strong correlation(r2> 0.9, P < 0.05).This study also composed an equation for ox LDL level in aortic tissue prediction. Factorial ANOVA found that there was a significant difference of ox LDL level in the interactions between duration and location, location and treatment, and also duration, location and treatment(P < 0.01). Administration of darapladib was able to reduce levels of ox LDL in serum,aortic tissue and foam cell significantly(P < 0.05, P < 0.05 and P < 0.01, subsequently).Conclusions: Ox LDL level is location-dependent and duration-dependent. As a feasible early diagnosis, we can predict ox LDL level in aortic tissue by its level in serum. Though Lp-PLA_2 expression was unsignificant, Lp-PLA_2 inhibition by darapladib can reduce oxidative stress and inflammation in atherogenesis.
基金This work was supported by the National Nature Science Foundation of China(31672361)the National Key R&D Program of China(2019YFE0120400).
文摘The eicosanoid signaling pathway mediates insect immune reactions to a wide range of stimuli. This pathway begins with the biosynthesis of arachidonic acid (AA) from the hydrolysis of phospholipids catalyzed by phospholipase A_(2) (PLA_(2)). We report here that the PLA_(2) inhibitor, dexamethasone (DEX), impaired the innate immune response including nodulation, encapsulation, and melanization in Ostrinia furnacalis larvae, while AA partially reversed these effects of DEX. We cloned a full-length complementary DNA encoding a PLA_(2), designated as OfsPLA_(2), from O. furnacalis. The open reading frame of OfsPLA_(2) encodes a 195-amino acid residue protein with a 22-residue signal peptide. Sequence alignment analyses indicated that O. furnacalis PLA_(2) might be a Group III secretory PLA_(2). The highest transcript levels of OfsPLA_(2) were detected in the fat body, and its transcript levels increased dramatically after infection with Escherichia coli, Micrococcus luteus, or Beauveria bassiana. Recombinant OfsPLA_(2) significantly induced prophenoloxidase (PPO) activation in larval hemolymph in the presence of Ca^(2+) and encapsulation of agarose beads. Injection of recombinant OfsPLA_(2) into larvae resulted in increased transcript levels of attacin, defencin, and moricin-3 genes. Our results demonstrate the involvement of the eicosanoid signaling pathway in the innate immune response of O. furnacalis larvae and provide new information about the roles of O. furnacalis secretory PLA_(2) in activating PPO and antimicrobial peptide production.
