RESUMO
Objective To evaluate the role of phosphatidylinositol 3-kinase ( PI3K)∕protein kinase B ( Akt) signaling pathway in propofol-induced reduction of intestinal ischemia-reperfusion ( I∕R) injury in rats. Methods Thirty-two healthy male Sprague-Dawley rats, aged 2-3 months, weighing 225-275 g, were divided into 4 groups ( n=8 each) using a random number table method: sham operation group ( Sham group), intestinal I∕R group ( I∕R group), propofol group ( P group), and PI3K inhibitor wortmannin plus propofol group ( W+P group) . Intestinal ischemia was induced by occluding the superior mesenteric ar-tery for 45 min followed by 2 h of reperfusion to establish the model of intestinal I∕R injury. Propofol was in-travenously infused at a rate of 20 mg·kg-1 ·h-1 starting from the onset of reperfusion until the end of reper-fusion in group P. Wortmannin 15 μg∕kg was intravenously injected at 25 min before reperfusion, and propofol was intravenously infused at a rate of 20 mg·kg-1 ·h-1 starting from the onset of reperfusion until the end of reperfusion in group W+P. Rats were sacrificed at 2 h of reperfusion, and small intestinal tissues were obtained for microscopic examination of pathologic changes of intestinal mucosa and for determination of wet∕dry weight ratio (W∕D ratio), malondialdehyde (MDA) content (by thiobarbituric acid colorimetric method) , superoxide dismutase ( SOD ) activity ( using xanthine oxidase method ) , myeloperoxidase ( MPO) activity ( by MPO assay) , and phosphorylated Akt ( p-Akt) expression ( by Western blot) . Intes-tinal damage was assessed and scored according to Chiu. Results Compared with group Sham, Chiu' s score, W∕D ratio, MDA content and MPO activity were significantly increased, the SOD activity was de-creased, and p-Akt expression was down-regulated in group I∕R (P<0. 05). Compared with group I∕R, Chiu's score, W∕D ratio, MDA content and MPO activity were significantly decreased, the SOD activity was increased, and p-Akt expression was up-regulated in group P (P<0. 05). Compared with group P, Chiu's score, W∕D ratio, MDA content and MPO activity were significantly increased, the SOD activity was decreased, and p-Akt expression was down-regulated in group W+P (P<0. 05). Conclusion The mechanism by which propofol reduces intestrnal I∕R injury is related to activating PI3K∕Akt signaling path-way and inhibiting inflammatory and oxidative stress responses in rats.
RESUMO
Aim To explore the antagonistic effect of nimodipine (Nim) on dibutyl phthalate (DBP)-in-duced learning and memory impairment in KM mice. Methods Thirty-six male KM mice were treated with saline (control), 50 mg • kg-1 DBP, 2 mg • kg-1 Nim, and DBP + Nim lasted for 28 days. The latency of KM mice in each group was measured. Levels of calmodulin (CaM), calmodulin/calmodulin-dependent protein kinase II ( CaMKII ) , protein kinase C (PKC) , cytochrome C (Cyt C) and caspase-3 in hippocampus of KM mice in each group were detected. And expressions of ERK1/2 and p-ERKl/2 were evaluated. In addition, the pathological changes of hipp-ocampal CAI region were also analyzed by HE, Nissl staining, and TUNEL assay. Results Compared with 50 mg • kg-1 DBP group, the learning and memory im-pairment of KM mice in DBP + Nim group was alleviated, the pathological damage and apoptosis in CA1 region of hippocampus were reduced, the levels of PKC, Cyt C, caspase-3 and p-ERKl/2 decreased, while the levels of CaM and CaMKII increased accordingly (P < 0.05). Conclusions DBP affects Ca2 +-related proteins and up-regulates p-ERKl/2 expression, inducing hippocampal neuronal damage and apoptosis, whereas Nim can improve DBP-induced learning and memory impairment in KM mice, which may be related to the ability of Nim to reduce the levels of p-ERKl/2 and caspase-3 in brain tissues of mice after DBP exposure by blocking DBP-induced Ca2+ concentration.