Dexmedetomidine protects cardiac microvascular endothelial cells from the damage of ogd/r through regulation of the pparδ-mediated autophagy.

BACKGROUND: Dexmedetomidine (Dex) exerts an effective therapeutic role in numerous diseases associated with ischemia/reperfusion (I/R) injury via its anti-apoptosis properties. Therefore, this study explores the cardioprotective effects of Dex in cardiac microvascular endothelial cells (CMECs) in response to oxygen-glucose deprivation and re-oxygenation (OGD/R) injury and its potential mechanism. MATERIAL AND METHODS: CMECs were pretreatment with different concentration of Dex, then exposed to OGD/R. Cell viability was measured with CCK-8 assay. Apoptosis was evaluated by flow cytometry, and apoptosis-related protein was determined by Western blot. Autophagy was assessed by transmission electron microscopy and autophagy-related proteins. Besides, the role peroxisome proliferator-activated receptors (PPARδ) in Dex-mediated anti-apoptosis property was validated with agonist and antagonist. RESULTS: OGD/R significantly decreased cell viability, increased reactive oxygen species, caused disorder of autophagy, and increased apoptosis in CMECs. Dex enhanced the viability of the OGD/R-treated CMECs and effectively decreased reactive oxygen species production. Autophagy in CMECs was activated by Dex, as evidenced by the increase in the ratio of LC3B-II/I, expression level of Beclin1 and number of autophagosomes in the OGD/R-induced CMECs. The mechanistic investigation indicated that PPARδ antagonist GW501516 aggravated cell damage following OGD/R, while PPARδ agonist GW6471 partly abolished the Dex-mediated protective effects. CONCLUSIONS: Dex activated the PPARδ-AMPK-PGC-1α pathway-mediated autophagy in CMECs, therefore to inhibit excessive apoptosis induced by OGD/R. Dex may potentially be a therapeutic intervention for myocardial I/R injury.

[Protective effect of early application of lytic cocktail on small intestine of severely scalded rats].

OBJECTIVE: To study the protective effect of early application of lytic cocktail on small intestine of severely scalded rats. METHODS: Sixty-six male SD rats were divided into sham injury group (SI, n=6), scald group (S, n=30) and scald+lytic cocktail group (SL, n=30) according to the random number table. After anesthesia, rats in the latter 2 groups were inflicted with 30% full-thickness scald, while rats in S group were sham scalded with 37 degrees C water. Resuscitation was carried out by intraperitoneal injection with 2 mLxkg(-1)x%TBSA(-1) lactated Ringer's solution in all rats; meanwhile 12 mL/kg lytic cocktail [1 mL pethidine (50 mg/mL)+1 mL chlorpromazine (25 mg/mL)+1 mL promethazine (25 mg/mL)+125 mL saline] was hypodermically injected to rats in SL group, while 12 mL/kg saline was injected into rats in the other 2 groups. Samples of blood and small intestine were harvested from S and SL groups at post scald hour (PSH) 3, 6, 12, 24, 48 and from SI group at PSH 3, with 6 rats in each group at each time point. Pathological changes in intestine were observed, and the expression of intercellular adhesion molecule 1 (ICAM-1) and CD68 were determined with immunohistochemistry at PSH 24 for S and SL groups and at PSH 3 for SI group. Plasma levels of D-lactate, diamine oxidase (DAO), IL-1beta, TNF-alpha, IL-10 were determined with ELISA. Data were processed with one-way analysis of variance. RESULTS: (1) At PSH 24, mild hemorrhage, inflammatory cell infiltration and epithelial cell shedding were observed in small intestinal mucosa of rats in S group. Compared with S group, the intestinal villi of SL group were arranged regularly without obvious hyperemia and edema. (2) Expression levels of ICAM-1 and CD68 [(1.69+/-0.27)%, (0.80+/-0.09)%] in S group were significantly higher than those in SI group [(0.77+/-0.10)%, (0.30+/-0.05)%, with F value respectively 77.303 and 66.933, P<0.05 or P < 0.01] and SL group [(0.53+/-0.09)%, (0.32+/-0.06)%, with F value respectively 77.303 and 66.933, P values all below 0.01]. (3) D-lactate levels of rats in SL group were significantly lower than those of rats in S group at PSH 12, 24 (with F value respectively 20.936 and 19.854, P values all below 0.01), while DAO levels of rats in SL group were significantly lower than those of rats in S group at PSH 3, 12 (with F value respectively 21.930 and 11.342, P values all below 0.05). (4) The levels of IL-1beta and TNF-alpha in S group were significantly higher than those of SI group at each time point (P values all below 0.01). The levels of IL-1beta and TNF-alpha in SL group were significantly higher than those of S group at PSH 6, 12 and 24 (with F value respectively 96.517, 17.365, 79.715 and 21.328, 17.682, 28.424, P<0.05 or P<0.01). IL-10 level in SL group was higher than that in S group at each time point, and the differences were statistically significant at PSH 6 and 24 (with F value respectively 8.668, 19.634, P < 0.05 or P<0.01). CONCLUSIONS: Early administration of lytic cocktail can attenuate edema and injury of intestinal mucosa in severely scalded rats. The mechanism may lie in that it can reduce the expression of ICAM-1 in intestinal mucosa, decrease the number of intestinal inflammatory cells and regulate the levels of inflammatory cytokines.