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Objective To investigate the role of hypoxia-inducible factor-1α/ hexokinase Ⅱ (HIF-1α/HKⅡ) signaling pathway in the inhibition of hypoxia/reoxygenation (H/R)-induced apoptosis in the rat cardiomyocytes by hypoxic preconditioning (HPC).Methods Primarily cultured cardiomyocytes obtained from the neonatal rats were seeded in culture dishes at the density of 5× 105cells/ml.The cardiomyocytes were attached to the wall for 72 h and then randomly divided into 6 groups (n=15 each) using a random number table:control group (group C);group H/R;group HPC;HIF-1o inhibitor YC-1 group (group YC-1);group HPC + YC-1;dimethyl sulfoxide (DMSO) group.The ceils were exposed to D-Hank solution saturated with 95％ N2 and 5％ CO2 for 4 h,and then cultured in the normal culture atmosphere for 2 h.The cells in YC-1 and DMSO groups were incubated in the culture medium containing 10 μmol/l YC-1 and 0.1％ DMSO (100 μl) for 24 b,respectively.HPC was induced by 3 cycles of 10 min hypoxia followed by 30 min reoxygenation,and H/R injury model was then established in group HPC.In group HPC+YC-1,the cells were incubated for 5 min in the M199 culture medium supplemented with 10 μmol/L YC-1 and 10％ fetal bovine serum,and the other treatments were similar to those previously described in group HPC.After the end of treatments,the apoptosis in cardiomyocytes was detected by TUNEL,the expression of HIF-1α,HKⅡ and cytochrome c was detected by Western blot,and the mitochondrial membrane potential was quantitatively measured using fluorescence.Apoptotic rate was calculated.Results Compared with group C,the apoptotic rate was significantly increased,the mitochondrial membrane potential was significantly decreased,and the expression of HIF-1α,HKⅡ and cytochrome c was significantly up-regulated in group H/R (P＜0.05).Compared with group H/R,the apoptotic rate was significantly decreased,and the mitochondrial membrane potential was significantly increased,and the expression of HIF-1αt and HKⅡ was significantly up-regulated,and the expression of cytochrome c was significantly down-regulated in group HPC (P＜0.05).Compared with group HPC,the apoptotic rate was significantly increased,the mitochondrial membrane potential was significantly decreased,the expression of HIF-1α and HKⅡ was significantly down-regulated,and the expression of cytochrome c was significantly up-regulated in group HPC+YC-1 (P＜0.05).Conclusion The mechanism by which HPC inhibits H/R-induced apoptosis in rat cardiomyocytes is associated with activation of HIF-1α/HKⅡ signaling pathway.
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Objective To investigate the effect of deproteinised calf serum enteric-coated capsules (DCSECC) on cognitive function of patients with epilepsy.Methods Sixty-six patients were randomly divided into two groups including experimental group who received DCSECC 5 mg/d,3 times a day and antiepileptics,and control group who received antiepileptics.To detect the cognitive function by means of Wechlors memory scale (WMS),Montreal cognitive assessment (MoCA),event related potentials (P300) latency period and malondialdehyde (MDA) before treatment and after treatment for 1,2,3 months,and compared with 33 healthy subjects controls (healthy group).Results Compared with healthy group,the scores of memory quotient (MQ) and MoCA were signifiantly decreased in experimental group and control group [(80.4 ± 14.2),(79.6 ± 13.9) scores vs.(103.2 ± 30.1) scores; (13.5 ± 4.5),(12.9 ± 3.9) scores vs.(28.8 ±8.7) scores],in the mean time,P300 latency period and MDA were signifiantly prolonged [(380.8 ± 49.7),(389.5 ± 50.4) ms vs.(309.8 ± 44.7) ms ; (5.0 ± 1.8),(4.8 ± 1.7) μ mol/L vs.(2.2 ± 0.6) μ mol/L],there was significant difference (P ＜ 0.05).Compared with the control group after treatment for 3 months,the scores of MQ and MoCA in experimental group [(96.5 ± 18.3) scores,(26.8 ± 7.7) scores] were increased and P300 latency period [(321.3 ±36.1) ms] was shortened,there were significant differences (P ＜ 0.05).The level of MDA decreased significantly in experimental group after 2,3 months treatment[(3.02 ± 1.04),(2.99 ± 1.01) μ mol/L],there was significant difference(P＜ 0.05).The scores of MQ and MoCA in control group after treatment had no significant difference compared with before treatment (P ＜ 0.05).Conclusions The cognitive function in patients with epilepsy is decreased.DCSECC medical treatment can improve the cognitive function by means of antioxidant activity.
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To investigate effects of l% l-acetylforskoin (l-aF) suspension eye-drops administeredtopically on intraocular pressure (IOP) in rabbits and men, and observe the loca l irritation of the drug． l% l-aF suspension eye-drops was prepared and was instilled into one of e yes while the corresponding vehicle into the contralateral eye as control． IOP was measured b y pneumatonometer before and after administration． l%1-aF suspension eye-drops s ig nificantly reduced IOP in rabbits reaching the maximum reduction of 2.2 mmHg and lasting a t least 3 hours． But it didnt show significant effects in men． There was little local irritati on neither in rabbits nor in men． l% l-aF suspension eye-drops significantly reduced IOP in normal rabbit s, but not in men． No local irritation was observed in rabbits and in men．