Objective To explore the effect of erythropoietin (EPO) attenuating apoptosis in old rat hippocampal neuronal cells exposed to sevoflurane and the role of toll like receptor 4.Methods Twenty months old SD rats,male,550-750 g,in accordance with the random number table,were divided into 3 groups (n =9):control group (group C),sevoflurane treatment (group S),and sevoflurane plus EPO treatment (group ES).The rats in group S and ES were subjected to inhale 4％ sevoflurane for 6 h,but the rats in group C were inhaled air-oxygen only.The rats in group ES were injected with EPO into caudal vein at 24 h,48 h,and 72 h after sevoflurane exposure.The cognitive ability was assessed by Morris water maze test;the effects of hippocampal apoptosis were assessed by TUNEL assays;the expressions of TLR4 mRNA was measured by RT-PCR assay;mitochondrial membrane potential (MMP) was assessed by JC-1 fluorescence;the expressions of APP and Aβ were assessed by western blot.Results Compared with group C,there were significant increases of escape latency period,neuronal apoptosis,TLR4 mRNA,and APP and Aβ expression,but a decrease of MMP in group S (P＜0.05).Compared with group S,there were significant decreases of escape latency period,neuronal apoptosis,TLR4 mRNA,and APP and Aβ expression,but a increase of MMP in group ES (P＜0.05).Conclusion The attenuation of rat hippocampal neuronal apoptosis induced by EPO could be associated with inhibition of TLR4,improvement of MMP,as well as inhibition of APP and Aβ activity.

Objective To evaluate the role of mitochondrial ATP sensitive potassium ( mito-KATP ) channel in dexmedetomidine-induced inhibition of subarachnoid hemorrhage ( SAH )-caused programmed cell death ( PCD) in cardiomyocytes of rats. Methods On hundred and twenty clean-grade healthy male Sprague-Dawley rats, aged 9-10 weeks, weighing 350-400 g, were divided into 5 groups ( n=24 each) using a random number table method: sham operation group ( group Sham ) , SAH group, SAH plus dexmedetomidine group ( group SD) , 5-HD plus SAH and dexmedetomidine group ( group HSD) and 5-HD plus SAH group ( group HS) . The rats were subjected to SAH by intracranial vascular puncture after being anesthetized with pentobarbital sodium. Dexmedetomidine 5 μg∕kg was infused for 10 min via the jugular vein starting from the time point after intracranial vascular puncture, followed by a continuous infusion of 5μg·kg-1 ·h-1 for 1 h in SD and HSD groups. 5-HD 30 mg∕kg was intraperitoneally injected at 1 h before intracranial vascular puncture in HSD and HS groups. Blood samples were collected from the abdominal aor-ta at 24 h after intracranial vascular puncture for determination of serum cardiac troponin I ( cTnI) concen-trations. The animals were then sacrificed, and myocardial specimens were collected for determination of PCD rate ( by TUNEL) , reactive oxygen species ( ROS) activity ( by DCFH-DA assay) , and expression of cleaved caspase-3, cleaved caspase-1 and interleukin-1beta ( IL-1β) ( by Western blot) . Results Com-pared with group Sham, the serum concentrations of cTnI, PCD rate and ROS activity were significantly in-creased, and the expression of cleaved caspase-3, cleaved caspase-1 and IL-1βwas up-regulated in SAH, SD, HSD and HS groups ( P<0. 05) . Compared with group SAH, the serum concentrations of cTnI, PCD rate and ROS activity were significantly decreased, and the expression of cleaved caspase-3, cleaved caspase-1 and IL-1βwas down-regulated in group SD, and the serum concentrations of cTnI, PCD rate and ROS activity were significantly increased, and the expression of cleaved caspase-3, cleaved caspase-1 and IL-1βwas up-regulated in group HS ( P<0. 05) . Compared with group SD, the serum concentrations of cT-nI, PCD rate and ROS activity were significantly increased, and the expression of cleaved caspase-3, cleaved caspase-1 and IL-1β was up-regulated in group HSD ( P<0. 05) . Compared with group HSD, the serum concentrations of cTnI, PCD rate and ROS activity were significantly increased, and the expression of cleaved caspase-3, cleaved caspase-1 and IL-1βwas up-regulated in group HS ( P<0. 05) . Conclusion mito-KATP channel is involved in dexmedetomidine-induced inhibition of PCD in cardiomyocytes of rats with SAH.

Objective To evaluate the role of Toll-like receptor 4 (TLR4) signaling pathway in sevoflurane anesthesia-induced cognitive dysfunction in aged rats.Methods Twenty-seven SPF healthy male Sprague-Dawley rats,aged 20 months,weighing 550-750 g,were divided into 3 groups (n =9 each) using a random number table:control group (C group),sevoflurane anesthesia group (S group) and TLR4 antagonist plus sevoflurane anesthesia group (TS group).TLR4 monoclonal antibody 30 μl was injected into the lateral cerebral ventricle in group TS,and the equal volume of serum containing no antibody was injected into the lateral cerebral ventricle in C and S groups.At 10 min after completion of injection,S and TS groups inhaled the mixture of 4％ sevoflurane and 30％ oxygen for 6 h,and group C only inhaled the mixture of air and oxygen.Morris water maze test was performed at 24 h after the end of sevoflurane anesthesia.The animals were sacrificed after completion of Morris water maze test,brains were removed and hippocampi were isolated for determination of nerve cell apoptosis (using TUNEL) and expression of activated caspase-3 (using immunofluorescent staining).Nerve cell apoptosis rate was calculated.The expression of high-mobility group box 1 protein (HMGB1) mRNA in hippocampi was measured by Northern blot assay at 6 h after the end of sevoflurane anesthesia.The expression of amyloid precursor protein (APP) and amyloid beta protein (Aβ) in hippocampi was assessed by Western blot at 24 h after the end of sevoflurane anesthesia.Results Compared with C group,the escape latency was significantly prolonged,nerve cell apoptosis rate was increased,the expression of activated caspase-3,HMGB1 mRNA,APP and Aβ was up-regulated in group S,and nerve cell apoptosis rate was increased,the expression of activated caspase-3,HMGB1 mRNA,APP and Aβ was up-regulated (P＜0.05),and no significant change was found in the escape latency in group TS (P＞0.05).Compared with S group,the escape latency was significantly shortened,nerve cell apoptosis rate was decreased,and the expression of activated caspase-3,HMGB1 mRNA,APP and Aβ was down-regulated in group TS (P＜0.05).Conclusion Activation of TLR4 signaling pathway is involved in the mechanism of sevoflurane anesthesia-induced cognitive dysfunction in aged rats.