Asarinin has been found to prolong allograft survival and inhibit post-transplant immune rejection via the Toll-like receptor (TLR) signaling pathway. However, the underlying mechanism is not completely understood. Therefore, elucidating the possible pathophysiological role of asarinin in the TLR signaling pathway is essential. Here, dendritic cells were isolated from Sprague–Dawley® rats and cultured with splenocytes from Wistar rats treated with asarinin, lipopolysaccharide (LPS), and/or dimethyl sulfoxide. mRNA expression of TLR-2, TLR-4, myeloid differentiation factor 88 (MyD88), and nuclear factor kB (NF-kB) was determined using real-time polymerase chain reaction. Interleukin (IL)-6 and IL-12 levels were examined using an enzyme-linked immunosorbent assay. LPS resulted in an increase in the expression of TLR-2 rather than TLR-4 and MyD88. Furthermore, it inhibited the secretion of IL-6 and IL-12. MyD88 can be silenced after lentiviral transduction, and LPS can activate MyD88, whereas asarinin can inhibit this kind of activation. The effect of LPS and asarinin on TLR-4 could only be achieved when MyD88 was not silenced by lentivirus transduction. Therefore, asarinin might suppress TLR-4-mediated activation via the MyD88-dependent pathway. Overall, asarinin has a pre-application effect in inhibiting graft rejection.

目的:心房颤动(Atrial fibrillation,AF)是最常见的心律失常之一,其发生机制目前尚未完全阐明.多项研究表明脂肪因子(Adipokines)中的瘦素(leptin)、内脂素(Visfatin)与心血管疾病的关系密切,本研究拟探讨瘦素、内脂素与心房颤动的关系.方法:本研究通过收集检测AF组、窦性心律组外周血及心外膜脂肪组织,检测瘦素、内脂素分泌水平来探讨瘦素、内脂素与AF发生的相关性.结果:房颤组血清内脂素的平均浓度为15.95±10.44ng/mL,窦性心律组为20.28±12.90ng/mL(P=0.169);房颤组血清瘦素的平均浓度为1.48ng/mL,窦律组为2.56 ng/mL(P=0.0027),窦性心律组血清瘦素水平明显高于心房颤动组;心外膜脂肪组织中,瘦素在房颤组中的表达量显著低于窦性心律组(P=0.032),内脂素在两组中的表达无显著统计学差异(P=0.06).结论:临床患者外周血血清及心外膜脂肪组织中高水平的瘦素可能降低房颤的发生率,然而,内脂素与房颤可能不具有相关性.

Background Ischemic stroke is a serious cardiovascular disease with high morbidity and mortality rates that affects millions of people worldwide.Currently, the only therapy with proven efficacy for acute ischemic stroke is alteplase, however, it still has many shortcomings and limitations. Therefore,we screen new compounds from traditional Chinese medicine to explore their efficacy against ischemic reperfusion injury. Procyanidins, a natural productextracted from grapes seed, which have been shown can ameliorate cerebral ischemic injury. However, the underlying mechanism is still not very clear. Theaim of this study was to investigate the effect of procyanidins on middle cerebral artery occlusion/reperfusion (MCAO/R)-mediated cerebral ischemic injuryand its underlying possible mechanisms. Methods SD rats were used to evaluate the effect of procyanidins on MCAO/R induced cerebral ischemic injury in vivo. Histological analysis was used toassess neuronal apoptosis. Cell signaling was assayed by Western blot. Results In this study, we found that procyanidins can significantly ameliorate the middle cerebral artery occlusion/reperfusion (MCAO/R)-mediatedneurological deficits, and relieved brain edema, cerebral infarction volume, histopathological damage and apoptosis in rats. In addition, procyanidins canalso markedly inhibit MCAO/R and oxygen-glucose deprivation/reoxygenation (OGD/R)-mediated activation of TLR4-p38-NF-κB-NLRP3 signalingpathway in vitro and in vivo. Moreover, procyanidins can inhibit MCAO/R and OGD/R-induced the production of inflammatory cytokines such asinterleukin-1β (IL-1β) in vitro and in vivo. Besides, treatment with TLR4 inhibitor (Cli-095) in BV2 cell also shows the same effect. Conclusion Altogether, these data suggested that procyanidins exerted a potential neuroprotective effect may by inhibit the TLR4-p38-NF-κB-NLRP3signaling pathway in the brain in MCAO/R rats.