期刊
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
卷 390, 期 12, 页码 1189-1200出版社
SPRINGER
DOI: 10.1007/s00210-017-1417-9
关键词
Endocannabinoid system; Chronic cerebral hypoperfusion; Neuroinflammation; NF-kappa B pathway
资金
- National Natural Science Foundation of China [81271212, 81601146]
The present study explored the protective effects of cannabinoid receptor agonist WIN55,212-2 (WIN) and fatty acid amide hydrolase inhibitor URB597 (URB) against neuroinflammation in rats with chronic cerebral hypoperfusion (CCH). Activated microglia, astrocytes, and nuclear factor kappa B (NF-kappa B) p65-positive cells were measured by immunofluorescence. Reactive oxygen species (ROS) was assessed by dihydroethidium staining. The protein levels of cluster of differentiation molecule 11b (OX-42), glial fibrillary acidic protein (GFAP), NF-kappa B p65, inhibitor of kappa B alpha (I kappa B-a), I kappa B kinase a/beta (IKK a/beta), phosphorylated IKK a/beta (p-IKK a/beta), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-alpha, and interleukin-1 beta (IL-1 beta) were examined by western blotting or enzyme-linked immunosorbent assay. All the protein levels of OX-42, GFAP, TNF-a, IL-1 beta, COX-2, and iNOS are increased in CCH rats. WIN and URB downregulated the levels of OX-42, GFAP, TNF-alpha, IL-1 beta, COX-2 and iNOS and inhibited CCH-induced ROS accumulation in CCH rats, indicating that WIN and URB might exert their neuroprotective effects by inhibiting the neuroinflammatory response. In addition, the NF-kappa B signaling pathway was activated by CCH in frontal cortex and hippocampus, while the aforementioned changes were reversed by WIN and URB treatment. These findings suggest that WIN and URB treatment ameliorated CCH-induced neuroinflammation through inhibition of the classical pathway of NF-kappa B activation, resulting in mitigation of chronic ischemic injury.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据