Objective:To investigate the effect of aucubin(AU)on mitochondrial autophagy in the hippocampus of ischemic stroke(IS)rats by regulating the pten-induced kinase protein 1(PINK1)/cytoplasmic E3-ubiquitin ligase(Parkin)signaling pathway.Methods:The IS rat model was established by middle cerebral artery occlusion(MCAO),and was randomly divided into IS group,low-dose AU group(AU-L),medium-dose AU group(AU-M),high-dose AU group(AU-H),and high-dose AU combined with 3-MA group(AU-H+3-MA).The rats without liga-tion were used as the Sham surgery group.Zea Longa score was used to evaluate the neurological function of rats.TTC staining was used to detect the percentage of cerebral infarction volume.The microstructures of mitochondria were observed by transmission electron microscopy,and the changes of autophagy protein-microtubule associated protein light chain 3B(LC3B)and p62 were detected by immunohistochemistry.Hippocampal apoptosis was detected by TUNEL.PINK1/Parkin-related protein expression in hippocampus was detected by Western blot.Results:Neurological function score of IS rats was increased(P＜0.05),cerebral infarction was observed by TTC staining,the expression of mito-chondrial autophagy protein p62 in hippocampus was up-regulated(P＜0.05),the expression of LC3B was down-regu-lated(P＜0.05),the number of autophagosomes was decreased(P＜0.05),and apoptosis in hippocampus was in-creased(P＜0.05),the expression of PINK1 and ARKIN protein in hippocampus was down-regulated(P＜0.05).After AU intervention,the neural function score of rats was decreased,the percentage of cerebral infarction volume was reduced,the positive expression of p62 in hippocampus was down-regulated(P＜0.05),the positive expression of LC3B was up-regulated(P＜0.05),and the number of autophagosomes was increased(P＜0.05),the apoptosis of hippocampus was decreased(P＜0.05),and the expression of PINK1 and ARKIN protein in hippocampus was in-creased(P＜0.05).3-MA blocked the therapeutic effect of AU and aggravated the nerve injury in rats.Conclusion:AU promotes hippocampal mitochondrial autophagy and improves neurological damage in IS rats by activating the PINK1/Parkin signaling pathway.

Objective:To investigate the effect of aucubin(AU)on mitochondrial autophagy in the hippocampus of ischemic stroke(IS)rats by regulating the pten-induced kinase protein 1(PINK1)/cytoplasmic E3-ubiquitin ligase(Parkin)signaling pathway.Methods:The IS rat model was established by middle cerebral artery occlusion(MCAO),and was randomly divided into IS group,low-dose AU group(AU-L),medium-dose AU group(AU-M),high-dose AU group(AU-H),and high-dose AU combined with 3-MA group(AU-H+3-MA).The rats without liga-tion were used as the Sham surgery group.Zea Longa score was used to evaluate the neurological function of rats.TTC staining was used to detect the percentage of cerebral infarction volume.The microstructures of mitochondria were observed by transmission electron microscopy,and the changes of autophagy protein-microtubule associated protein light chain 3B(LC3B)and p62 were detected by immunohistochemistry.Hippocampal apoptosis was detected by TUNEL.PINK1/Parkin-related protein expression in hippocampus was detected by Western blot.Results:Neurological function score of IS rats was increased(P＜0.05),cerebral infarction was observed by TTC staining,the expression of mito-chondrial autophagy protein p62 in hippocampus was up-regulated(P＜0.05),the expression of LC3B was down-regu-lated(P＜0.05),the number of autophagosomes was decreased(P＜0.05),and apoptosis in hippocampus was in-creased(P＜0.05),the expression of PINK1 and ARKIN protein in hippocampus was down-regulated(P＜0.05).After AU intervention,the neural function score of rats was decreased,the percentage of cerebral infarction volume was reduced,the positive expression of p62 in hippocampus was down-regulated(P＜0.05),the positive expression of LC3B was up-regulated(P＜0.05),and the number of autophagosomes was increased(P＜0.05),the apoptosis of hippocampus was decreased(P＜0.05),and the expression of PINK1 and ARKIN protein in hippocampus was in-creased(P＜0.05).3-MA blocked the therapeutic effect of AU and aggravated the nerve injury in rats.Conclusion:AU promotes hippocampal mitochondrial autophagy and improves neurological damage in IS rats by activating the PINK1/Parkin signaling pathway.

Objective To evaluata the effect of dexmedetomidine on myocardial ischemia-reperfusion injury in the patients undergoing cardiac surgery with cardiopulmonary bypass:a meta-analysis.Methods We searched the China Integrated Knowledge Resources Database,Chinese Biomedical Database,Wanfang Database,Weipu,PubMed,Cochrane Library (from inception to July 2015) to identify randomized controlled trials involving dexmedetomidine-induced cardioprotection in the patients undergoing cardiac surgery with cardiopulmonary bypass.The following data were extracted from the trials included:the mean arterial pressure and heart rate at breast bone splitting,the spontaneous recovery of heart beat during surgery,the plasma concentrations of creatine kinase-MB and cardiac troponin I at 6,24 and 48 h after surgery,and heart rate at 24 h after surgery.Meta-analysis was conducted using the Cochrane Collaboration's RevMan 5.3 software.Results Twelve prospective randomized controlled trials involving 750 patients were included in this meta-analysis.The patients were divided into 2 groups:dexmedetomidine group (n =376)and control group (n =374).Compared with control group,the plasma caradiac troponin I concentrations at 6,24,and 48 h after surgery,and creatine kinase-MB concentrations at 6 and 24 h after surgery were significantly decreased,the mean arterial pressure and heart rate were decreased at breast bone splitting,heart rate was decreased at 24 h after surgery,and the percentage of spontaneous recovery of heart beat was increased in dexmedetomidine group (P＜0.05).Conclusion Dexmedetomidine can mitigate myocardial ischemia-reperfusion injury in the patients undergoing cardiac surgery with cardiopulmonary bypass.

Objective To evaluate the effects of extremity ischemic preconditioning on liver injury after cardiac valve replacement with cardiopulmonary bypass (CPB).Methods Sixty ASA physical status Ⅱ or Ⅲ patients (NYHA Ⅱ or Ⅲ), weighing 44-72 kg, with ejection fraction≥40％, schedule for elective cardiac valve replacement with CPB, were randomly divided into 2 groups (n =30 each) using a random number table: control group (group C) and extremity ischemic preconditioning group (group E).Immediately after anesthesia induction, an auto-inflatable cuff was placed under the right lower extremity, and was inflated to 300 mmHg to induce ischemia (oxygen saturation at the finger tip undetected or foot pulse untouched on the operated side) which was preceded by 3 cycles of 5 min ischemia-5 min reperfusion in group E.Before anesthesia induction (T0) , and at 2, 12, 24, and 72 h, and 7 days after operation (T1-5) , blood samples were taken from the right internal jugular vein for determination of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities.The expression of serum miR-122 was detected at T0-4 by real-time reverse transcriptase polymerase chain reaction.Results Compared with the value at T0, the serum ALT and AST activities were significantly increased at T2-4, and the expression of miR-122 was up-regulated at T1-3 in the two groups (P＜0.05).Compared with group C, the serum ALT and AST activities were significantly decreased at T2-4, and the expression of miR-122 was down-regulated at T1-3in group E (P＜0.05).Conclusion Extremity ischemic preconditioning can mitigate liver injury after cardiac valve replacement with CPB.

Objective To evaluate the effect of remote ischemic perconditioning on systemic inflammatory response in the patients undergoing cardiac valve replacement with cardiopulmonary bypass (CPB).Methods Forty adult patients undergoing cardiac valve replacement under CPB were randomly divided into 2 groups (n =20 each):control group (group C) and remote ischemic preconditioning group (group R).Anesthesia was induced with iv injection of midazolam,fentanyl,vecuronium.The patients were mechanically ventilated after endotracheal intubation.Anesthesia was maintained with iv injection of midazolam,fentanyl,vecuronium and inhalation of sevoflurane.Three cycles of 5-min ischemia and 5-rmin reperfusion were performed on the fight lower extremity immediately after aortic occlusion by means of a tourniquet in group R.A tourniquet was only placed under the right lower extremity in group C.Before CPB and at 0,6 and 24 h after termination of CPB (T1-4),blood samples were obtained from the right internal jugular vein for determination of levels of serum intercellular adhesion molecule-1 (ICAM-1),IL-6 and TNF-α.Results The levels of serum ICAM-1,IL-6 and TNF-α were significantly lower in group R than in group C (P ＜ 0.05).Compared with the baseline value at T1,the levels of serum ICAM-1,IL-6 and TNF-α were significantly increased at T2 and T3 in both groups,serum ICAM-1 and IL-6 levels were increased at T4 in group C,while serum IL-6 level was increased at T4 in group R (P ＜ 0.05).The levels of serum ICAM-1,IL-6 and TNF-α were significantly decreased at T3 and T4 than at T2 in both group (P ＜ 0.05).The levels of serum ICAM-1,IL-6 and TNF-α were significantly lower at T4 than at T3 in both groups (P ＜ 0.05).Conclusion Remote ischemic perconditioning can alleviate the systemic inflammatory response in patients undergoing cardiac valve replacement with CPB.