ABSTRACT
Objective To study the effects of TGFβ-activated kinase-1 (TAK1)mediated cell autophagy after global cerebral ischemia-reperfusion (IR ) in rats.Methods Seventy-two male Kunming rats were randomly divided into six groups:control group (group C),sham operation group (group S),ischemia-reperfusion group (group IR),TAK1 shRNA lentivirus group (group T),nega-tive lentivirus group (group Y)and normal saline group (group NS)(n = 12 each).The rats in groups T,Y and NS received cerebral ventricles injection of TAK1 shRNA lentivirus,negative lenti-virus and normal saline 10 μl two weeks before preparing animal model.Using thread embolism of the right middle cerebral artery occlusion (MCAO)to cause focal ischemia for 2 h and released for 24 h for reperfusion in groups IR,T,Y and NS.The common carotid arteries were separated but not liga-ted in group S,the rest of the procedure as the same as group IR.The rats of each group were evalua-ted by neurological severity scores (NSS)24 h after reperfusion,the cerebral infarct volume was measured with the method of TTC and the expression of TAK1,LC3Ⅱ/LC3Ⅰ,Beclin1 and p62 pro-tein in rat hippocampus were determined by using Western blot.Results The infarct volume and NSS in groups IR,T,Y and NS were significantly higher than those in group C (P <0.05).The infarct volume and NSS in group T were significantly lower than those in group IR (P <0.05).TAK1 pro-tein of hippocampus in groups IR,Y and NS was significantly higher than that in group C (P <0.05).TAK1 protein of hippocampus in group T were significantly lower than that in group IR (P <0.05).LC3Ⅱ/LC3 Ⅰand Beclin1 protein of hippocampus in groups IR,T,Y and NS were signifi-cantly higher than those in group C,and the p62 protein of hippocampus in groups IR,T,Y and NS was significantly lower than that in group C (P <0.05).The LC3 Ⅱ/LC3 Ⅰand Beclin1 in group T were significantly lower than those in group IR,and the p62 protein of hippocampus in group T was significantly higher than that in group C (P < 0.05 ).Conclusion TAK1 mediated cell autophagy takes part in the mechanism of brain ischemia-reperfusion injury in rats.
ABSTRACT
Objective To evaluate the changes in the expression of adaptor protein containing pleck-strin homobgy domain, phosphotyrosine-binding domain and a leucine zipper motif 1(APPL1)during renal fibrosis in a mouse model of renal ischemia-reperfusion(I∕R)injury. Methods Twenty-four male C57BL∕6 mice, aged 8 weeks, weighing 20-25 g, were divided into 2 groups(n=12 each)using a random number table: sham operation group(S group)and renal I∕R group.The model of renal I∕R injury was established by clipping the bilateral renal pedicles for 30 min followed by reperfusion in group I∕R.Six mice were selected at 2 days of reperfusion, and venous blood samples were collected for determination of serum concentrations of blood urea nitrogen and creatinine.The animals were then sacrificed, the renal specimens were obtained for microscopic examination of tubular necrosis with a light microscope, and the damage to the renal tubules was scored using a semi-quantitative method.Six mice were sacrificed at 14 days of reperfusion, and the renal specimens were obtained for assessment of the degree of renal fibrosis(using picric acid-sirius red staining) and for determination of the expression of collagen type 1, fibronectin and α-smooth muscle actin in renal tis-sues(by Western blot or immunofluorescence method). At 2 and 14 days of reperfusion, the expression of APPL1 in renal tissues was detected by Western blot and the expression of APPL1 mRNA in renal tissues by real-time polymerase chain reaction. Results Compared with group S, the serum concentrations of blood u-rea nitrogen and creatinine, scores of renal tubular damage and degree of renal fibrosis were significantly in-creased at 2 days of reperfusion, the expression of collagen type 1, fibronectin and α-smooth muscle actin in renal tissues was up-regulated at 14 days of reperfusion, and the expression of APPL1 protein and mRNA was up-regulated at 2 and 14 days of reperfusion in group I∕R(P<0.05). Conclusion Up-regulated expression of APPL1 may be involved in the process of renal fibrosis in a mouse model of renal I∕R injury.
ABSTRACT
Objective To investigate the efficacy of dexmedetomidine combined with target-controlled infusion (TCI) of propofol and remifentanil for fiberoptic bronchoscopy in the elderly patients.Methods Forty ASA Ⅱ or Ⅲ patients,aged 65-75 yr,with body mass index of 20-30 kg/m2,scheduled for elective fiberoptic bronchoscopy,were randomly divided into 2 groups (n =20 each):control group (group C) and dexmedetomidine group (group D).In group D,a loading dose of dexmedetomidine 0.5/μg/kg was injected at 10 min before induction of anesthesia,followed by infusion at 0.5 μg· kg-1 · h-1 until the end of fiberoptic bronchoscopy.While the equal volume of normal saline was given instead in group C.Anesthesia was induced with TCI of propofol and remifentanil.The target effect-site concentration (Ce) of propofol was 3 μg/ml.When the plasma concentration and Ce were balanced,TCI of remifentanil (target Ce 4 ng/ml) was started.The fiberoptic bronchoscope was placed after consciousness was lost and then the Ces of propofol and remifentanil were adjusted to 1-3 μg/ml and 2-4 ng/ml,respectively.MAP,HR and OAA/S score were recorded before induction (T0),immediately after induction (T1),when the tip of fiberoptic bronchoscope reached the glottis (T2) and carina (T3),at the end of bronchoscopy (T4)and 10 min after the end of bronchoscopy (T5).The consumption of propofol and remifentanil,duration of bron-choscopy,emergence time,adverse cardiovascular events and side effects such as hyoxemia,nausea and vomiting,regurgitation and aspiration were recorded.Results Compared with group C,OAA/S score at T5 and the consumption of propofol and remifentanil was reduced,and emergence time was shortened,and the incidence of hypotension and hyoxemia was decreased in group D (P ＜ 0.05).No patients developed side effects such as hyoxemia,nausea and vomiting,regurgitation and aspiration in both groups.Conclusion Dexmedetomidine (infusion at 0.5 μg·kg-1 ·h-1 after a loading dose of 0.5 μg/kg) combined with TCI of propofol and remifentanil can be safely and effectively used for fiberoptic bronchoscopy in the elderly patients.