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Objective To evaluate the effects of different doses of oxycodone on renal ischemiareperfusion (I/R) injury in rats.Methods Forty adult male Sprague-Dawley rats, weighing 220-300 g, aged 10-13 weeks, were randomly divided into 5 groups (n =8 each) using a random number table: sham operation group (group S), group I/R, and low, medium and high doses of oxycodone groups (OL, OM and OH groups).After the rats underwent right nephrectomy, the renal I/R was induced by occlusion of the left renal artery and vein for 45 min with atraumatic microclips followed by 3 h reperfusion in I/R, OL, OM and OH groups.In group S, right nephrectomy was performed, and the left renal artery, vein and ureter were isolated without occluding blood flow.In OL, OM and OH groups, oxycodoue 2, 4, and 6 mg/kg were infused intravenously, respectively, immediately after onset of ischemia.At 3 h of reperfusion, blood samples were taken from the abdominal aorta to determine the concentrations of serum blood urea nitrogen (BUN) and creatiniue (Cr) concentrations.After blood sampling, the animals were sacrificed, and the left kidneys were removed for determination of tumor necrosis factor-alpha (TNF-α) , interleukin-6 (IL-6) and IL-8 and IL-10 contents (by using enzyme-linked immunosorbent assay), and malondialdehyde (MDA) content (by thiobarbituric acid method), and superoxide dismutase (SOD) activity (using xanthine oxidase method).Results Compared with group S, the serum BUN and Cr concentrations, and contents of TNF-α, IL-6, IL-8 and MDA in renal tissues were significantly increased, and the IL-10 content and SOD activity in renal tissues were decreased in the other four groups (P＜0.05).Compared with group I/R, the serum BUN and Cr concentrations, and contents of TNF-α, IL-6, IL-8 and MDA in renal tissues were significantly decreased, and the IL-10 content and SOD activity in renal tissues were increased in OL, OM and OH groups (P＜0.05).The serum BUN and Cr concentrations, and contents of TNF-α,IL-6, IL-8 and MDA in renal tissues were gradually decreased, and the IL-10 content and SOD activity in renal tissues were gradually increased with increasing dosage of oxycodone in OL, OM and OH groups (P＜ 0.05).Conclusion Oxycodone 2, 4, and 6 mg/kg can alleviate renal I/R injury in a dose-dependent manner in rats, and the mechanism is related to inhibition of inflammatory responses and oxidative stress response.
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Objective To evaluate the effect of oxycodone preconditioning on liver injury induced by intestinal ischemia-reperfusion (I/R) in rats and the role of different opioid receptors.Methods Fiftyfour adult male Sprague-Dawley rats, weighing 200-300 g, were randomly divided into 9 groups (n =6 each) using a random number table: sham operation group (group S), group I/R, oxycodone preconditioning group (group OP) , μ receptor antagonist CTOP group (group CTOP) , δ receptor antagonist naltrindole group (group NTD), κ receptor antagonist nor-binaltorphimne group (group BNI), CTOP + oxycodo ne preconditioning group (group CTOP+OP) , naltrindole + oxycodone preconditioning group (group NTD+ OP) , and nor-binaltorphimne + oxycodone preconditioning group (BNI+OP).The model of intestinal I/R was established by occlusion of the superior mesenteric artery for 45 min followed by 2 h reperfusion in anesthetized rats.The superior mesenteric artery was only exposed, but not occluded in group S.In OP,COTP+OP, NTD+OP and BNI+OP groups, oxycodone 0.5 mg/kg was injected intravenously at 10 min prior to ischemia.COTP 1 mg/kg and naltrindole 5 mg/kg were injected intravenously at 20 min prior to ischemia in COTP+OP and NTD+OP groups, respectively.Nor-binaltorphimne 5 mg/kg was injected intravenously at 25 min prior to ischemia in group BNI+OP.In CTOP and NTD groups, the corresponding doses of CTOP and naltrindole were injected intravenously at 10 min prior to ischemia.In group BNI, the corresponding dose of nor-binaltorphimne was injected intravenously at 15 min prior to ischemia.The rats were sacrificed at 2 h of reperfusion, and left hepatic lobes were removed for microscopic examination and for detection of apoptosis in liver cells (using TUNEL).The apoptosis index (AI) was calculated.Results Compared with group S, the AI was significantly increased in the other groups (P＜0.05).Compared with group I/R, the AI was significantly decreased (P＜0.05) , and the pathological changes of livers were reduced in OP, COTP+OP, NTD+OP and BNI+OP groups, and no significant change was found in AI and pathological changes of livers in CTOP, NTD and BNI groups (P＞0.05).Compared with group OP, the AI was significantly increased (P＜0.05), and the pathological changes of livers were aggravated in COTP+ OP, NTD+OP and BNI+OP groups.There was no significant difference in AI and pathological changes of livers among groups COTP+OP, NTD+OP and BNI+OP (P＞0.05).Conclusion Oxycodone preconditioning can mitigate liver injury induced by intestinal I/R in rats, and μ, δ and κ receptors mediate the role with comparable effects.
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Objective To evaluate the influence of preconditioning with and anti-myosinmonoclonal antibody (mAb2G4)-nuclear factor-kappa B decoy oligodeoxynucleotide (ODN)-lipofectamine (lip) on hypoxia-reoxygenation (H/R) injury in H9c2 cardiomyocytes.Methods H9c2 cardiomyocytes were seeded in 6-well plate at the density of 1×105/ml (2 ml/well),and were divided into 3 groups (n=9 each) using a random number table:control group (group C),H/R group and mAb2G4-ODN-lip group (group MOL).The cells underwent 2 h of hypoxia in an air-tight bag,followed by 1 h reoxygenation.In MOL group,the cells were treated with mAb2G4-ODN-lip (2 μg ODN) for 4 h and then cultured in the common culture medium for 8 h before hypoxia.At the end of reoxygenation,proliferation of cells was measured using MTT assay,and the cells and supernatant of the culture medium were collected to determine the activity of lactate dehydrogenas (LDH),content of malondialdehyde (MDA),concentrations of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) (by ELISA).The rate of proliferation inhibition was calculated.Results Compared with group C,the rate of proliferation inhibition,LDH activity,MDA content,and concentrations of TNF-α and IL-6 were significantly increased in the other two groups.Compared with group H/R,the rate of proliferation inhibition,LDH activity,MDA content,and concentrations of TNF-α and IL-6 were significantly decreased in MOL group.Conclusion mAb2G4-ODN-lip can mitigate H/R injury in H9c2 cardiomyocytes.
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Objective To evaluate the effects of chronic exposure to sub-anesthetic concentrations of sevoflurane on memory function and homeostasis of mice.Methods Thirty-six healthy male Kunming mice,aged 40 days,weighing 25-30 g,were randomly assigned into 3 groups (n =12 each):control group (group C),0.1％ sevoflurane group (group L) and 0.5 ％ sevoflurane group (group H).The mice inhaled 0.1％ (group L) or 0.5％ sevoflurane (group H) between 18:00-6:00 (the next day) every night for 30 days.Water maze test was performed at 27-30 days of inhalation.Blood samples were collected from the left ventricle for blood gas analysis and for determination of blood electrolytes.Results There was no significant difference in swimming time in Water maze test,number of errors and blood gas analysis and blood electrolytes.Conclusion Chronic exposure to subanesthetic concentrations of sevoflurane has no significant effects on memory function and homeostasis of mice.
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Objective To investigate the efficacy and safety of Minilase-S on patients with dyspepsia.Methods A randomized,placebo-controlled,double blind and multicenter study was conducted.Two hundred and forty patients with dyspepsia symptoms(anorexia,fullness,abdominal discomfort and distension)were collected according to total symptom scores over 20 with visual analog scales.Each patient was randomly received either Minilase-S(2 capsules t.i.d)or placebo(2 capsules t.i.d)for 2 weeks.The symptoms scores were evaluated at treatment week 1,week 2,and 1 week after discontinued therapy.Results Two hundred and sixteen patients(105 patients in Minilase group and 111 patients in placebo group)finished the study.There was no difference in demographic data,anorexia,fullness,discomfort and distension score and the total symptom score between two groups.However,at treatment week 1,week 2 and 1 week after discontinued therapy,symptoms and total symptom score were significantly decreased in Minilase-S group compared to placebo group(all P value＜0.05).The total effective rates in treatment week 1,week 2 and 1 week after discontinued therapy were 64.76%,77.05%and 66.99%,respectinely,which were higer that those in placebo group(27.93%,37.84% and 29.36%,respectively)(P＜0.05).There was no severe side effects in both Minilase-S and placebo groups.Conclusions Minilase-S can significantly improve symptoms in patients with dyspepsia,which may be as one choice in the management of dyspepsia or in combined therapy.