Effects of isoflurane on angiogenesis and Smad signaling pathway in rats with focal cerebral ischemia/reperfusion / 中国药理学通报

ABSTRACT

Aim To investigate the effects of isoflu-rane on angiogenesis in rats with cerebral ischemia/reperfusion and the possible mechanism. Methods Forty healthy adult male Sprague-Dawley rats were randomly divided into sham operation group (Sham group) , ischemia-reperfusion group (I/R group) , isoflurane post-treatment group (ISO group) and isoflurane post-treatment + Smad3 specific inhibitor SIS3 HC1 group (ISO + SIS3 group). Rat middle cerebral artery occlusion model (MCAO) was established by suture method. After 24 h, Zea-Longa method was used to evaluate the neurological deficit of rats. HE staining was used to evaluate the pathological damage of brain tissues. Nissl staining was used to evaluate the surviving neurons in ischemic brain tissues. TUNEL staining was employed to assess the apoptosis of brain tissues. Immunofluorescence was applied to evaluate the expression levels of VEGF and CD34. Western blot analysis was used to detect the expression levels of p-Smad3, Smad3 , VEGF and CD34. Results Isoflurane significantly reduced the neurobehavioral score of rats, reduced the pathological damage of brain tissues, increased the number of normal neurons in the ischemic brain tissues, reduced the apoptotic cells in injured brain tissues, and enhanced the expression levels of p-Smad3, VEGF and CD34. Smad3 inhibitor re-versed the brain protective effect of isoflurane, aggravated cerebral ischemia-reperfusion injury, and inhibited the protein expression levels of p-Smd3 , VEGF and CD34. Conclusions Isoflurane can improve cerebral ischemia/reperfusion injury in rats, and its protective mechanism is related to activation of Smad signaling pathway, promotion of VEGF and CD34 protein expression , and promotion of angiogenesis.