ABSTRACT
Objective:To explore the effect of different doses of dexmedetomidine (Dex) on levels of tight-junction protein claudin-1 and diamine oxidase (DAO) in patients undergoing laparoscopic radical resection of gynecological malignant tumors.Methods:A total of 60 patients with gynecological malignant tumors who were scheduled to undergo laparoscopic radical resection under general anesthesia from January 2019 to January 2020 in the Second Hospital of Shanxi Medical University were selected, including 43 cases of cervical cancer (stageⅠ-Ⅱ A), 9 cases of ovarian cancer (stageⅠ A-Ⅲ C), and 8 cases of endometrial carcinoma (stageⅠ). Accroding to the random number table method, the patients were divided into control group (group C), low-dose Dex group (group D 1) and high-dose Dex group (group D 2), with 20 cases in each group. Patients in group D 1 were given Dex 0.5 μg·kg -1·h -1 by constant rate intravenous infusion pump after induction until 30 min before the end of operation. Patients in group D 2 were given Dex 1.0 μg·kg -1·h -1 by constant rate intravenous infusion pump after induction until 30 min before the end of operation. Group C adopted the same calculation method and received the same amount of 0.9% sodium chloride solution by infusion pump. At 10 min before induction (T 1), 1 hour after pneumoperitoneum (T 2) and 12 hours after pneumoperitoneum (T 3), 5 ml of brachial vein blood was collected from the patients, and the levels of claudin-1 protein, DAO and blood glucose were measured. Results:At T 1, T 2 and T 3, the expression levels of claudin-1 in group C were (77.05±17.61) pg/ml, (66.76±12.97) pg/ml and (55.93±12.71) pg/ml, and the difference was statistically significant ( F = 10.449, P<0.05); the expression levels of DAO in group C were (4.83±0.93) ng/ml, (5.62±1.01) ng/ml and (5.98±1.21) ng/ml, and the difference was statistically significant ( F = 6.139, P < 0.05); the levels of blood glucose in group C were (4.82±0.66) mmol/L, (7.55±0.94) mmol/L and (6.51±0.54) mmol/L, and the difference was statistically significant ( F = 70.197, P < 0.05). At T 2, the expression level of claudin-1 in group D 1 was (69.12±13.02) pg/ml, which was not significantly different from group C ( t = -0.575, P > 0.05); the expression level of claudin-1 in group D 2 was (76.36±14.89) pg/ml, which was higher than that in group C, and the difference was statistically significant ( t = -2.175, P < 0.05). At T 3, the expression levels of claudin-1 in group D 1 and group D 2 were (66.14±14.36) pg/ml and (73.37±16.93) pg/ml, which were higher than that in group C, and the differences were statistically significant ( t values were -2.380 and -3.682, both P < 0.05). The expression levels of DAO in group D 1 and group D 2 were (5.02±0.84) ng/ml and (4.91±0.93) ng/ml at T 2, and (5.29±0.86) ng/ml and (5.20±0.98) ng/ml at T 3, which were lower than those in group C, and the differences were statistically significant ( t values were 2.051, 2.295, 2.079 and 2.285, all P < 0.05). The levels of blood glucose in group D 1 and group D 2 were (7.10±0.66) mmol/L and (6.77±0.97) mmol/L at T 2, and (5.95±0.94) mmol/L and (5.93±0.74) mmol/L at T 3, which were lower than those in group C, and the differences were statistically significant ( t values were 2.565, 5.374, 2.293 and 2.765, all P < 0.05). Conclusion:Continuous infusion of Dex can inhibit the stress response caused by long-term CO 2 pneumoperitoneum in laparoscopic radical resection of gynecological malignant tumors, and adjust the changes of expression levels of claudin-1 protein and DAO, reduce the damage of intestinal mucosal cells, facilitate the recovery of intestinal function, and the effect of high-dose Dex is better than low-dose Dex.
ABSTRACT
AIM: To explore the protective effect and mechanism of dexmedetomidine on intestinal mucosal barrier injury in septic rats. METHODS: Forty eight SD rats were randomly divided into four groups (n=12): sham operation group (sham group), sepsis group (sepsis group), sepsis + dexmedetomidine group (DEX group), and sepsis + DEX + HIF-1ɑ inhibitor Bay87-2243 (Bay87-2243 group). Sepsis model was established by cecal ligation and perforation (CLP). The rats in both DEX and Bay87-2243 groups were given 30 μg/kg of DEX intraperitoneally 30 minutes before CLP and 2 hours after CLP; while the rats in Bay87-2243 group received oral gavage of Bay87-2243 (9 mg/kg) for 3 days before CLP. The other groups were intraperitoneally injected and orally with the same amount of normal saline. The HIF-1ɑ and the tight junction protein (tight junction protein, TJs) was detected by western blot; the plasma concentrations of diamine oxidase (DAO), intestinal fatty acid binding protein (FABP2) and D-lactic acid (D-LAC) were detected by ELISA; the morphological changes of intestinal mucosa were detected by HE staining. RESULTS: DEX significantly increased the expression level of HIF-1ɑ (P<0.05) on intestinal mucosa in rats with sepsis injury (P<0.05), thus ameliorated intestinal mucosal pathological injury, reduced Chiu's score (P<0.05), decreased intestinal mucosal permeability (P<0.05), and up-regulated TJs protein expression (P<0.05). Moreover, effect on sepsis induced intestinal mucosal injury of DEX was reversed by HIF-1ɑ Bay87-2243. CONCLUSION: DEX could protect against sepsis-induced intestinal mucosal injury by up-regulating HIF-1ɑ expression in rats.
ABSTRACT
Objective To evaluate the role of cholinergic anti-inflammatory pathway in dexmedeto-midine pretreatment-induced reduction of acute lung injury in a rat model of intestinal ischemia-reperfusion ( I∕R) . Methods Twenty-four healthy male Sprague-Dawley rats, aged 2-3 months, weighing 200-250 g, were divided into 4 groups ( n=6) using a random number table method: sham operation group ( S group) , intestinal I∕R group ( II∕R group ) , dexmetomidine group ( DEX group) and α7 nicotinic acetyl-choline receptor antagonistα-bungarotoxin (α-BGT) group (α-BGT group) . Intestinal I∕R was produced by occlusion of the superior mesenteric artery ( SMA) for 60 min followed by 120 min of reperfusion in anesthe-tized rats. Dexmetomidine 5 μg·kg-1 ·h-1 was injected via the tail vein at 1 h before operation in DEX group andα-BGT group. α-BGT 1μg∕kg was intraperitoneally injected at 15 min before dexmetomidine in-jection in α-BGT group. Rats were sacrificed at 120 min of reperfusion, and lung tissues were obtained for microscopic examination of pathological changes ( with a light microscope) and for determination of wet∕dry weight ratio ( W∕D ratio) , tumor necrosis factor-alpha ( TNF-α) and interleukin-6 ( IL-6) contents ( using enzyme-linked immunosorbent assay) , malondialdehyde ( MDA) content ( using thiobarbital acid method) and superoxide dismutase ( SOD) activity ( by xanthine oxidase method) . Results Compared with group S, the W∕D ratio and contents of MDA, TNF-αand IL-6 were significantly increased, and the SOD activi-ty was decreased in II∕R and α-BGT groups, and TNF-α and IL-6 contents were significantly increased in group DEX ( P<0. 05) . Compared with group II∕R, the W∕D ratio and contents of MDA, TNF-αand IL-6 were significantly decreased, SOD activity was increased (P<0. 05), and the pathological changes were significantly attenuated in group DEX. Compared with group DEX, the W∕D ratio and contents of MDA, TNF-α and IL-6 were significantly increased, SOD activity was decreased ( P<0. 05) , and the pathological changes were accentuated in group α-BGT. Conclusion Activation of cholinergic anti-inflammatory path-way is involved in the mechanism by which dexmedetomidine pretreatment reduces acute lung injury in a rat model of intestinal I∕R.
ABSTRACT
Objective To evaluate the effect of dexmedimidine on intestinal injury in rats with endotoxemia.Methods Twenty-four healthy adult male Sprague-Dawley rats,aged 2-3 months,weighing 200-250 g,were divided into 4 groups (n =6 each) using a random number table method:control group (group C),endotoxemia group (group E),dexmedimidine group (group D) and dexmedimidine plus α7 subunit-containing nicotinic acetylcholine receptor antagonist group (D +α-BGT group).The endotoxemia model was established by injecting lipopolysaccharide (LPS) 10 mg/kg via the femoral vein.Dexmedetomidine 40 μg/kg was injected and 15 min later LPS was intravenously injected in group D.Dexmedetomidine 40 μg/kg was intraperitoneally injected after intraperitoneal injection of α-bungarotoxin 1 μg/kg,and 15 min later LPS was intravenously injected in group D+o-BGT.Blood samples were collected from the abdominal aorta at 6 h after LPS injection for determination of the plasma interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) concentrations (by enzyme-linked immunosorbent assay).Rats were sacrificed after blood sampling,and intestinal tissues were obtained for examination of the pathological changes and for determination of the myeloperoxidase (MPO) activity (by chemical colorimetry) and expression of NF-κB p65 in nucleoprotein (by Western blot).Results Compared with group C,the plasma IL-6 and TNF-o concentrations and MPO activity in intestinal tissues were significantly increased,and the expression of NF-κB p65 in nucleoprotein was up-regulated in the other 3 groups (P＜0.05).Compared with group E,the plasma IL-6 and TNF-α concentrations and MPO activity in intestinal tissues were significantly decreased,the expression of NF-κB p65 in nucleoprotein was down-regulated (p＜0.05),and the pathological changes of intestinal tissues were significantly attenuated in group D.Compared with group D,the plasma IL-6 and TNF-α concentrations and MPO activity in intestinal tissues were significantly increased,the expression of NF-κB p65 in nucleoprotein was up-regulated (P＜0.05),and the pathological changes of intestinal tissues were accentuated in group D+α-BGT.Conclusion Dexmedetomidine can reduce the intestinal injury in rats with endotoxemia,and the mechanism may be related to activating cholinergic anti-inflammatory pathway and further inhibiting inflammatory responses.