1.Effect of dexmedetomidine pretreatment on ERK pathway during acute lung injury in a rat model of liver transplantation
Zhen ZHANG ; Gang XU ; Qiaorong DENG ; Xihua LU ; Xilong LI ; Yaping CUI ; Baofeng YANG
Chinese Journal of Anesthesiology 2016;36(9):1089-1093
Objective To evaluate the effects of dexmedetomidine pretreatment on extracellular sig?nal?regulated kinase ( ERK) pathway during acute lung injury in a rat model of liver transplantation. Meth?ods Sixty male Sprague?Dawley rats, weighing 235-250 g, were divided into 4 groups ( n=15 each) u?sing a random number table: sham operation group (group S), liver transplantation group (group LT), low?dose dexmedetomidine pretreatment group ( group LD ) and high?dose dexmedetomidine pretreatment group ( group HD) . In LT, LD and HD groups, the model of orthotopic liver transplantation was estab?lished, and the operation time was about 4 h. Dexmedetomidine 2?5 and 5?0μg·kg-1 ·h-1 were intrave?nously infused for 1 h starting from 1 h prior to clipping the hepatic artery and portal vein in LD and HD groups, respectively. The rats were sacrificed after the end of operation, and the lungs were removed for determination of wet to dry weight ratio ( W∕D ratio) , cell apoptosis and expression of ERK mRNA, ERK, phosphorylated ERK ( p?ERK) , Bcl?2 and Bax in lung tissues and for examination of the pathological chan?ges ( with light microscope) and ultrastructure of lung tissues ( with transmission electron microscope) . The
injured alveolus rate ( IAR) , apoptosis index ( AI) and ratio of Bcl?2 to Bax expression ( Bcl?2∕Bax ratio) were calculated. Results Compared to group S, the W∕D ratio, IAR, AI, expression of ERK?1 mRNA, ERK?2 mRNA, p?ERK, Bcl?2 and Bax and Bcl?2∕Bax ratio were significantly increased in LT, LD and HD groups ( P<0?05) . Compared to group LT, the W∕D ratio, IAR and AI were significantly decreased, the expression of ERK?1 mRNA, ERK?2 mRNA, p?ERK and Bcl?2 and Bcl?2∕Bax ratio were significantly increased, and the expression of Bax was significantly down?regulated in LD and HD groups (P<0?05). Compared to group LD, the W∕D ratio, IAR and AI were significantly decreased, the expression of ERK?1 mRNA, ERK?2 mRNA, p?ERK and Bcl?2 and Bcl?2∕Bax ratio were significantly increased, and the ex?pression of Bax was significantly down?regulated in group HD ( P<0?05) . The pathological changes of lung tissues were significantly attenuated in LD and HD groups as compared with group LT, and in group HD as compared with group LD. Conclusion The mechanism by which dexmedetomidine pretreatment mitigates cell apoptosis during acute lung injury is related to activation of ERK pathway in a rat model of liver trans?plantation.
2.Effect of penehyclidine hydrochloride on damage to non-ventilated lung in pediatric patients undergoing one-lung ventilation
Zhen ZHANG ; Gang XU ; Qiaorong DENG ; Xihua LU ; Xilong LI ; Yaping CUI ; Baofeng YANG
Chinese Journal of Anesthesiology 2016;36(5):531-534
Objective To evaluate the effect of penehyclidine hydrochloride on the damage to the non-ventilated lung in the pediatric patients undergoing one-lung ventilation (OLV).Methods One hundred and twenty pediatric patients of both sexes,aged 2-6 yr,with body mass index of 17-24 kg/m2,of American Society of Anesthesiologists physical status Ⅰ or lⅡ and New York Heart Association class Ⅰ or Ⅱ,undergoing elective lobectomy performed via video-assisted thoracoscope,were randomly divided into 2 groups (n=60 each) using a random number table:control group (group C) and penehyclidine hydrochloride group (group P).At 10 rmin before anesthesia induction,penehyclidine hydrochloride 0.05 mg/kg was injected intravenously in group P,and the equal volume of normal saline was given in group C.At 5 min after drug intervention (T0),immediately after onset of OLV (T1),at 60 min of OLV (T2),immediately after the end of OLV (T3),at the end of surgery (T4),and at 24 h after surgery (T5),venous blood samples were collected for determination of serum tumor necrosis factor-alpha (TNF-o),interleukin-6 (IL-6) and IL-8 concentrations by enzyme-linked immunosorbent assay.The specimens of normal lung tissues around the lung lobe to be resected were obtained at T1 and T3 for determination of the injured alveolus count (with a light microscope) and cell apoptosis (using TUNEL) and for examination of the ultrastructure of epithelial cells (with a transmission electron microscope).The injured alveolus rate (IAR) and apoptosis index (AI) were calculated.Results Compared to the value at T0,the IAR and AI were significantly increased at T3,the serum TNF-α,IL-6 and IL-8 concentrations were significantly increased at T2-5 (P<0.05),and the pathological changes were obvious in the two groups.Compared to group C,the IAR and AI were significantly decreased at T3,the serum TNF-α,IL-6 and IL-8 concentrations were significantly decreased at T2-5 (P<0.05),and the pathological changes were significantly reduced in group P.Conclusion Penehyclidine hydrochloride can attenuate the damage to the non-ventilated lung in the pediatric patients undergoing OLV,and the mechanism is probably related to inhibition of systemic inflammatory responses and cell apoptosis in lung tissues.
3.Effect of dexmedetomidine pretreatment on hippocampal endoplasmic reticulum stress-induced cell apoptosis after asphyxial cardiac arrest-resuscitation in rats
Zhen ZHANG ; Xihua LU ; Qiaorong DENG ; Meng GAO ; Baofeng YANG ; Yaping CUI ; Jia LI
Chinese Journal of Anesthesiology 2018;38(3):376-380
Objective To investigate the effect of dexmedetomidine pretreatment on hippocampal endoplasmic reticulum stress-induced cell apoptosis after asphyxial cardiac arrest-resuscitation in rats. Methods A total of 60 pathogen-free male Sprague-Dawley rats, aged 6-8 weeks, weighing 200-300 g, were divided into 3 groups (n= 20 each) by using a random number table: control group (C group), as-phyxial cardiac arrest-resuscitation group ( CA group) and dexmedetomidine pretreatment group ( Dex group). The anaesthetized rats were intubated with a 16G tracheal catheter which was connected to a rodent ventilator for mechanical ventilation. Cardiac arrest was induced by clamping the tracheal tube at the end of the exhalation until systolic blood pressure decreased to 25 mmHg lasting for 5 min, and then resuscitation was started. At 5 min before cardiac arrest, dexmedetomidine 4. 0 μg∕kg was intravenously injected in group Dex, and the equal volume of normal saline was given instead in C and CA groups. Rats were sacri-ficed at 6 h after successful resuscitation, brain tissues were removed for determination of wet to dry weight ratio ( W∕D ratio), and hippocampal tissues were obtained for examination of the pathological changes (with a light microscope) and ultrastructure (with an electron microscope) and for determination of cell ap-optosis (by TUNEL), expression of CCAAT∕enhancer-binding protein homologous protein (CHOP) and ac-tivated transcription factors (ATF4) and X-4 box binding protein 1 (XBP1) mRNA (by real-time polymer-ase chain reaction) and expression of CHOP, Bcl-2, Bax and caspase-3 (by Western blot). The apoptosis rate was calculated. Results Compared with group C, W∕D ratio of brain tissues was significantly in-creased, the apoptosis rate of hippocampal tissues was decreased, the expression of XBP-1, ATF4 and CHOP mRNA was up-regulated, the expression of CHOP, Bax and caspase-3 was up-regulated, and the expression of Bcl-2 was down-regulated in CA and Dex groups (P<0. 05). Compared with group CA, W∕D ratio of brain tissues was significantly decreased, the apoptosis rate of hippocampal tissues was decreased, the expression of XBP-1, ATF4 and CHOP mRNA was down-regulated, the expression of CHOP, Bax and caspase-3 was down-regulated, the expression of Bcl-2 was up-regulated (P<0. 05), and the pathological changes were significantly attenuated in group Dex. Conclusion The mechanism by which dexmedetomi-dine pretreatment mitigates brain injury after asphyxial cardiac arrest-resuscitation may be related to inhibi-ting cell apoptosis induced by endoplasmic reticulum stress in rats.
4.Efficiency and safety of Hydromorphone combined with Propofol therapy in painless gastroscopy combined with colonoscopy examination in elder patients
Zhen ZHANG ; Meng GAO ; Qiaorong DENG ; Xilong LI ; Yaping CUI ; Aimin FENG ; Shuanshuang HE ; Xihua LU
Chinese Journal of Geriatrics 2017;36(11):1224-1228
Objective To explore the clinical efficacy and safety of Hydromorphone combined with Propofol therapy in painless gastroscopy combined with colonoscopy examination in elder patients.Methods Sixty-one patients aged 65-80 years underwent a painless gastroscopy combined with colonoscopy examination in the Affiliated Tumor Hospital of Zhengzhou University from June 2015 to January 2016.The patients were randomly divided into the Hydromorphone combined with Propofol group (Group H,n=31) and the Fentanyl combined with propofol group (Group F,n=30).Results The levels (H vs F group) of VAS at 5,15,30 min after anesthetic recovery were lower in H group thanin F group[(2.4±0.5) vs (3.4±0.6),(2.0±0.5) vs (3.2±0.6),(1.6±0.4) vs (2.6±0.7) respectively,(all P<0.05)],and those of ramsay sedation scores at 5,15,30,45,and 60 min after anesthetic recovery were lower in H group than in F group[(2.6 ± 0.4) vs (3.3 ± 0.5),(2.3±0.5) vs (2.9±0.4),(2.1±0.3) vs (2.6±0.3),(1.9±0.3) vs (2.2±0.3),(1.8±0.3) vs (2.0±0.3) (all P<0.05)] respectively.Additionally,the incidence rates (H vs F group) of nausea and vomit (3.2% vs.26.7%),respiratory depression (0.0% vs.33.3%) and restlessness (6.5% vs.30.0%) within 60 min after anesthetic recovery were lower in the group H than in the group F (all P< 0.05).However,there were no statistical differences in the indexes of postoperative gastrointestinal function between two groups (all P>0.05).Conclusions The clinical efficiency of hydromorphone combined with propofol used in painless gastroscopy combined colonoscopy examination is favourable and safe without increasing postoperative adverse reactions in elder patients.Hydromorphone combined with propofol is superior to fentanyl combined with propofol as a general intravenous anesthesia.