Adipose proinflammatory cytokine expression through sympathetic system isassociated with hyperglycemia and insulin resistance in a rat ischemic strokemodel.

摘要

Patients who experience acute ischemic stroke may develop hyperglycemia, even in the absence of diabetes, but the exact mechanisms are still unclear. Adiposetissue secretes numerous proinflammatory cytokines and is involved in theregulation of glucose metabolism. This study aimed to determine the effects ofacute stroke on adipose inflammatory cytokine expression. In addition, becausesympathetic activity is activated after acute stroke and catecholamines canregulate the expression of several adipocytokines, this study also evaluatedwhether alterations in adipose proinflammatory cytokines following acute stroke, if any, were medicated by sympathetic system. Acute ischemic brain injury wasinduced by ligating the right middle cerebral artery and bilateral common carotidarteries in male adult Sprague-Dawley rats. Adipose tumor necrosis factor-alpha(TNF-alpha) and monocyte chemoattractant protein-1 (MCP-1) mRNA and protein levelswere determined by RT-PCR and enzyme-linked immunoassay, respectively. The strokerats developed glucose intolerance on days 1 and 2 after cerebral ischemicinjury. The fasting blood insulin levels and insulin resistance index measured byhomeostasis model assessment were higher in the stroke rats compared with thesham group. Epididymal adipose TNF-alpha and MCP-1 mRNA and protein levels wereelevated one- to twofold, in association with increased macrophage infiltrationinto the adipose tissue. When the rats were treated with a nonselectivebeta-adrenergic receptor blocker, propranolol, before induction of cerebral ischemicinjury, the acute stroke-induced increase in TNF-alpha and MCP-1 was blocked, andfasting blood insulin concentration and homeostasis model assessment-insulinresistance were decreased. These results suggest a potential role of adiposeproinflammatory cytokines induced by the sympathetic nervous system in thepathogenesis of glucose metabolic disorder in rats with acute ischemic stroke.