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Objective To evaluate the effect of doxepin on the expression of p38 mitogen-activated protein kinase (p38 MAPK) in the spinal cord of rats with neuropathic pain (NP).Methods Sixty clean-grade male Wistar rats in which intrathecal catheters were successfully implanted,weighing 200-250 g,were divided into 3 groups (n =20 each) by a random number table method:sham operation group (S group),NP group and doxepin group (D group).NP was induced by chronic constriction injury (CCI) to sciatic nerve.Doxepin 20 mmol/L (10 μl) was intrathecally injected at 3,7,14 and 21 days after CCI (T1-4) in group D.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured at 1 day before CCI (T0) and at T1-4.The rats were sacrificed after measurement of pain threshold at T4,and L4-6 segments of the spinal cord were removed for determination of the expression of p38MAPK protein by Western blot.Results Compared with S group,MWT was significantly decreased and TWL was shortened at T2-4,and the expression of p38MAPK protein was up-regulated in NP and D groups (P＜0.05).Compared with NP group,MWT was significantly increased and TWL was prolonged at T2-4,and the expression of p38MAPK protein was down-regulated in D group (P＜0.05).Conclusion The mechanism by which doxepin mitigates NP is related to down-regulating p38MAPK expression in the spinal cord of rats.
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Objective To observe the effect ofmitochondrial division inhibitor (Mdivi-1) on the neuronal apoptosis via mitochondria signaling pathways in rats after cerebral ischemia/reperfusion (I/R) and its possible mechanism.Methods Sixty male adult healthy Wistar rats were chosen and randomly divided into sham-operated group,vehicle group and Mdivi-1 pre-conditioning group (n=20); animal models of middle cerebral artery occlusion/reperfusion in the later 2 groups were established by a filament method in the left extemal-internal carotid artery.Rats were injected with 1.2 mg/kg Mdivi-1 in the Mdivi-1 pre-conditioning group and dimethyl sulfoxide in the vehicle group 15 minutes before the cerebral ischemia.After 24 h of reperfusion,apoptotic cell death was assessed by TUNEL staining,the cytochrome C expression (Cyt C) was detected by SABC immunohistochemical staining,the protein level of Cyt C in the cerebral issues was detected by Western blotting and the mRNA expression was measured by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR).Results The apoptosis rate (45.49％±0.77％),Cyt C positive cell rate (55.12％±1.47％) and protein and mRNA expressions of Cyt C (0.932 ±0.001,0.789±0.009) in the vehicle group were significantly higher that in the sham-operated group (4.16％±0.25％,4.22％±0.20％,0.395±0.002,0.467±0.003,P＜0.05).The apoptosis rate (45.49％±0.77％),Cyt C positive cell rate (55.12％±1.47％) and protein and mRNA expressions of Cyt C (0.594±0.002,0.523±0.004) in the Mdivi-1 pre-conditioning group were significantly decreased as compared with those in the vehicle group (P＜0.05).Conclusion Mitochondrial division inhibitor Mdivi-1 might reduce neuronal apoptosis by inhibiting mitochondria cytochrome C apoptotic pathway to protect cerebral against ischemia/ reperfusion injury.
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Objective To evaluate the safety and immunogenicity of split influenza vaccine (Anflu(R) ). Methods An open-labeled clinical trial was carried out in adults aged 18-60 years and elders aged over 60 years from August to September, 2010 in Shenyang, Liaoning province. One dose of split influenza vaccine was administered and adverse events were observed. Serum samples were obtained prior to vaccination and 21 days post vaccination. A/H1N1, A/H3N2 and B antibodies against influenza virus were measured using micro-hemagglutination inhibition (HI) assay. Results A total of 130 subjects were recruited and 120 paired serum samples were obtained. The overall rate of adverse events was 2.3% (3/130) and all of them with systemic reaction. No single serious adverse event was reported. 21 days after the vaccination, the sero-conversion rates of A/H1N1, A/H3N2 and B antibodies against influenza virus among adults were 82.5%, 93.7% and 92.1%, respectively. The Geometric Mean Titer (GMT) ratios were 20.2, 32.0 and 11.4, while the sero-protection rates were 92.1%, 98.4% and 98.4%, respectively. The sero-conversion rates of antibodies among elders were 89.5%, 91.2% and 87.7%, with the GMT ratios as 23.9, 39.8 and 15.1, respectively. The seroprotection rates were 93.0%, 94.7% and 96.5%,respectively. Conclusion All indexes ofA/H1N1,A/H3N2 and B antibodies exceeded the licensure criteria established by the EU Committee for Medicinal Products for Human Use,proving the trial vaccine Anflu(R) with good safety and immunogenicity.