ABSTRACT
Myofibrillogenesis regulator-1 (MR-1) is a novel protein involved in cellular proliferation, migration, inflammatory reaction and signal transduction. However, little information is available on the relationship between MR-1 expression and the progression of atherosclerosis. Here we report atheroprotective effects of silencing MR-1 in a model of Ang II-accelerated atherosclerosis, characterized by suppression focal adhesion kinase (FAK) and nuclear factor kappaB (NF-κB) signaling pathway, and atherosclerotic lesion macrophage content. In this model, administration of the siRNA-MR-1 substantially attenuated Ang II-accelerated atherosclerosis with stabilization of atherosclerotic plaques and inhibited FAK, Akt, mammalian target of rapamycin (mTOR) and NF-kB activation, which was associated with suppression of inflammatory factor and atherogenic gene expression in the artery. In vitro studies demonstrated similar changes in Ang II-treated vascular smooth muscle cells (VSMCs) and macrophages: siRNA-MR-1 inhibited the expression levels of proinflammatory factor. These studies uncover crucial proinflammatory mechanisms of Ang II and highlight actions of silencing MR-1 to inhibit Ang II signaling, which is atheroprotective.
Subject(s)
Animals , Mice , Angiotensin II , Angiotensins , Arteries , Atherosclerosis , Cell Proliferation , Focal Adhesion Protein-Tyrosine Kinases , Gene Expression , In Vitro Techniques , Macrophages , Muscle Development , Muscle, Smooth, Vascular , NF-kappa B , Plaque, Atherosclerotic , RNA, Small Interfering , Signal Transduction , SirolimusABSTRACT
Objective To investigate the effects of chronic restraint stress on learning and memory in Wistar and Sprague-Dawley (SD) rats.Methods Healthy adult male Wistar rats (n=6) and Sprague-Dawley rats (n=6) were subjected to restraint stress 10 h daily for 28 days.After that, all rats were tested for recognition memory by novel object recognition test , and spatial memory and working memory by Morris water maze test .Results After restraint for 10 h daily for 28 days, the restraint rats of the two strains demonstrated lower discrimination index (DI)than the control group, but on-ly SD rats showed significant difference ( P<0.05 ) .The restraint SD rats showed higher escape latency than the control rats, and on the 5th day the difference became significant (P<0.05), and there was no significant difference between Wistar restraint and control rats .The working memory test showed that restraint SD rats exibited longer escape latency than the control rats (P<0.05), while Wistar rats didn’t show significant difference between the two groups .Conclusions The results of this study demonstrate that the impairments of learning and memory in SD rats subjected to restraint 10 hour per day for 28 days are more serious than that in the Wistar rats .Therefore , SD rats may be a better choice as an animal model to study the effects of chronic restraint stress on learning and memory impairment .
ABSTRACT
Objective To observe the effect of Huoluojiangu Capsule(HJC) on anti-inflammatory experiment.Methods The anti-inflammatory experimental models were established in three kinds of rats with pleuritis,the swellen sole of the foot and the PGE_2 content in inflammatory tissues,respectively.Results The swollen reaction in the sole of foot in rats induced by egg white was lessoned with the treatment of low,middle and high dosage of HJC.Compared with the blank control group,the treatment is effective in low dosage group and evidently effective in groups of middle and high dosage after 30 min(P0.05),respectively.Compared with the blank control group,the effect of HJC on the PGE_2 content in the inflammatory tissues of middle and high dosage groups was significant(P