Objective It has been shown that protein kinase C (PKC), especially PKCy is involved in the nociceptive processing at the spinal level. This study was designed to investigate the effects of intrathecal (IT) morphine on PKCy immuno-reactivity in the spinal dorsal horn in a rat model of incisional pain. Methods Twenty-four male SD rats weighing 250-300 g were anesthetized with intraperitoneal pentobarbital 40 mg?kg-1. PE-10 catheter was inserted intrathecally to the lumbar region according to Yaksh. Five days later an incision of 1cm long was made in the plantar region of left hindpaw, parallel to the muscle under isoflurane anesthesia according to Brennan. The animals were randomly divided into 4 groups with 6 animals in each group : group Ⅰ sham-operation group received IT artificial cerebro-spinal fluid (ACSF) 20 ?l and 30 min later inhaled 1.4% isoflurane for S min but no incision was made; group Ⅱ received ACSF 20 ?l IT 30 min before incision was made; group Ⅲ post-incisional morphine group received morphine 5 ?g IT 30 min after incision and group Ⅳ pre-incisional morphine group received morphine 5 ?g IT 30 min before incision. The animals were sacrificed under general anesthesia 2 h after incision. The L4-5 segment of spinal cord was removed for determination of the expression of PKC? in the spinal dorsal horn by immuno-histochemical method.Results In group Ⅱ the PKC?-IR gray density in the spinal dorsal horn of the operated side was significantly higher than that of contralateral side and that in group Ⅰ( P

Objective Substance P and its receptor are thought to play an important role in the mechanisms of pain The purpose of this study was to investigate the effects of intrathecal (IT) morphine on substance P expression in the dorsal horn of spinal cord in a rat model of incisional pain Methods Sixteen male SD rats weighing 250 300g were randomly divided into four groups of 4 animal each: in group Ⅰ (sham operation) 30 min after IT normal saline(NS) 20 ?l 1 4% isoflurane was inhaled for 5 min but no incision was made; in group Ⅱ (control group) 30 min before incision NS 20 ?l was given IT; in group Ⅲ (postoperative analgesia group) morphine 5 ?g (10 ?l) was given IT 30 min after incision; group Ⅳ ( preemptive analgesia group) morphine 5 ?g (10 ?l) was given IT 30 min before incision The animals were anesthetized with intraperitoneal pentobarbital sodium 40 mg?kg -1 PE 10 catheter was inserted intrathecally to the lumbar region according to method of Yaksh 5 days later incision of 1 cm long was made in the plantar region of left hindpaw parallel to the muscle under isoflurane anesthesia according to the method of Brennan Pain behavior was assessed by a cumulative pain score Immuno histochemistry technique was used to measure the expression of substance P Results IT morphine given either before or after incision decreased the cumulative pain scores Incision made in the plantar region of left hindpaw increased substance P expression in the ipsilateral dorsal horn of spinal cord (0 62?0 07 vs 0 40?0 09) In group Ⅳ increase in substance P expression in the dorsal horn of spinal cord was inhibited Conclusions The analgesia provided by preemptive IT morphine is possibly mediated via the decrease in substance P in the dorsal horn of spinal cord

Objective To detect the change of hemorrheology and prethromboticstate markers levels in patients with obstructive sleep apnea hypopnea syndrome (OSAHS) and to explore the pathogenic mechanisms of cardio-cerebrovascular thromboembolic diseases in OSAHS patients. Methods Polysomnography was performed in 86 patients with OSAHS and in 20 control subjects matched for age and body mass index. The patients with OSAHS were divided into mild group , moderate group , and severe group according to the apnea hypopnea index (AHI). Hemorrheology and prethromboticstate markers levels were measured in all the subjects for correlation analysis. Results The whole blood viscosity, erythrocyte aggregation index, and erythrocyte electrophoresis time in mild OSAHS group , moderate OSAHS group and severe OSAHS group were significantly higher than those in the control group. The whole blood viscosity, erythrocyte aggregation index, and erythrocyte electrophoresis time were also significantly different between the three OSAHS groups , increasing with the severity of OSAHS. Plasma viscosity was not significant difference between OSAHS groups and the control group. Plasma D-D , AT-Ⅲ and vWF levels were also not significant difference between OSAHS groups and the control group. Conclusions The change of hemorrheology in OSAHS patients may contribute to the vulnerability of patients to cardio-cerebrovascular thromboembolic diseases.

Objective To evaluate the role of p38 mitogen-activated protein kinase (p38MAPK) in the spinal cord in the development of persistent postoperative pain evoked by skin/muscle incision and retraction (SMIR) and the relationship with Toll-like receptor 4 (TLR4).Methods One hundred and twenty male SpragueDawley rats,weighing 200-250 g,aged 2 months,in which intrathecal catheters were successfully implanted,were randomly divided into 5 groups (n =24 each) using a random number table:sham operation group (group S),SMIR group,SMIR + dimethyl sulfoxide (DMSO) group (group DMSO),SMIR + p38MAPK inhibitor SB203580 group (group SB203580) and SMIR + TLR4 small interference RNA (siRNA) group (group TLR4siRNA).The rats were anesthetized with intraperitoneal chloral hydrate 400 mg/kg.The skin and superficial muscle of the medial thigh were incised and a small pair of retractors inserted.This tissue was retracted for 1 h causing potential stretch of the saphenous nerve.2％ DMSO 10 μl and SB203580 5 μg were injected intrathecally at 30 min before operation and 1-12 days after operation in DMSO and SB203580 groups,respectively.TLR4siRNA 2 μg was administered intrathecally at 1 day before operation and 1-12 days after operation once a day in group TLR4siRNA.Mechanical paw withdrawal threshold to von Frey filament stimulation (MWT) was measured at 1 day before operation and 1,3,7,12 and 22 days after operation.Four rats in each group were sacrificed after measurement of MWT at each time point,and the L4-6 segments of the spinal cord were obtained for detection of the expression of phosphorylated p38MAPK (p-p38MAPK) by Western blot analysis.Results Compared with group S,MWT was significantly decreased after operation,and the expression of p-p38MAPK was up-regulated after operation in SMIR and DMSO groups.Compared with group SMIR,MWT was significantly increased after operation,and the expression of p-p38MAPK was down-regulated after operation in SB203580 and TLR4siRNA groups,and no significant changes in MWT and p-p38MAPK expression were found at each time point in group DMSO.Conclusion TLR4-triggered activation of p38MAPK in spinal cord is involved in the development of SMIR-evoked persistent postoperative pain in rats.

ObjectiveTo investigate the role of NF-κB signaling pathway in the spinal cord in persistent postoperative pain evoked by skin/muscle incision and retraction (SMIR) in rats.MethodsNinety male SD rats weighing 200-250 g in which intrathecal (IT) catheter was successfully implanted without complication were randomly divided into 3 groups ( n =30 each):group sham operation ( group S ) ; groups SMIR and group pyrrolidine dithiocarbarnate (a NF-κB inhibitor) (group PDTC).Persistent postoperative pain was evoked by SMIR according to the method described by Flatters in groups SMIR and PDTC.PDTC 10 ng in 10 μl was injected IT over 30 s once a day for 7 consecutive days after operation in group PDTC.Mechanical paw withdrawal threshold to von Frey filament stimulation (MWT) was measured at 1 d before (T0,baseline) and 1,3,7,12 and 22 d after surgery (T1-5).Five animals in each group were sacrificed at each time point after MWT measurement and their lumbar segments of the spinal cord were removed for determination of TNF-α content (by ELISA).ResultsSMIR significantly decreased MWT after operation at T1-5 and increased TNF-α content in the spinal cord at T3-5.PDTC significantly attenuated SMIR-induced hyperalgesia and increase in TNF-α content in the spinal cord.Conclusion NF-κB signaling pathway in the spinal cord plays an important role in the development of SMIR-induced persistent postoperafive pain in rats.

Objective To investigate the correlation between epicardial fat thickness and non dipper hypertension.Methods A total of 150 subjects was included in the study,of which 50 were in the non dipper hypertension group,the same in the non dipper hypertension group and the healthy control group.History collection and routine laboratory tests,ultrasonic measurement of epicardial fat thickness,and 24 hour ambulatory blood pressure monitoring were carried on all subjects.Epicardial fat thickness between groups was compared to primarily analyze the correlation of epicardial fat thickness and non dipper type hypertension.The optimal screening positive value in epicardial fat thickness of non dipper type primary hypertension was obtained by receiver operating characteristic (ROC) curve and maximum Youden index.Results When non dipper hypertension group and non-dipper hypertension group were compared,epicardial fat thickness was significantly increased [(6.30 ± 0.94) mm vs (5.92 ± 0.75) mm,P ＜ 0.05],as compared dipper hypertension group to healthy group,the epicardial fat thickness was significantly increased [(5.92 ±0.75)mm vs (5.50 ±0.13)mm,P ＜0.05].Epicardial fat thickness and non dipper type primary hypertension were linearly related (r =0.43,P ＜ 0.05),and epicardial fat thickness in diagnosis of non dippers primary hypertension optimal screening positive value was 6.01 mm.Conclusions There is a close relationship of epicardial fat thickness and non dipper hypertension.

Objective To analyze the effectiveness evaluation of cardiovascular drugs which have been developed on the CYP2C9 target protein by multi-layer fuzzy evaluation technology .Methods The multi-layer fuzzy evaluation method was used to evaluate the effectiveness of cardiovascular drugs interacting with the CYP 2C9 protein and to construct the index system that affects drug efficacy .Results and Conclusion The index system was used to study such cardiovascular drugs as valsartan and to score the drug effectiveness of individual samples .The results were consistent with actual drug treatment and were well confirmed .The results contribute to evaluation of personalized medication .

ObjectiveTo investigate the effects of morphine preconditioning on myocardial ischemiareperfusion (I/R) injury and the expression of phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2)in rats with chronic heart failure.MethodsForty-eight healthy male SD rats weighing 220-250 g were randomly divided into 6 groups ( n =8 each):control group (group C),sham operation group (group S),I/R group and preconditioning with low,median and high doses of morphine groups (groups MP1-3 ).Chronic heart failure was induced by iv edriamycin 2.0 mg/kg once a week for 6 weeks in groups S,I/R and MP1-3.Left ventricular end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD) were measured using ultrasound,and left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were calculated at the end of 14th day after the end of adriamycin administration.Blood samples from the carotid artery were collected after ultrasonography for determination of the plasma brain natriuretic peptide (BNP) concentration.Myocardial I/R was induced by 30 min occlusion of left anterior descending branch of coronary artery followed by 120 min reperfusion at 2 day after ultrasonography in groups I/R and MP1-3.In groups MP1-3,iv morphine 0.015,0.030 and 0.050 mg/kg were repeated 3 times at 5 min interval at 30 min before ischemia respectively,while normal saline 5 ml/kg was given in group I/R.The animals were sacrificed at the end of reperfusion in groups S,I/R and MP1-3,and the hearts were removed to measure the area at risk (AAR),infarct size (IS),and IS/AAR ratio was calculated.The p-ERK1/2 expression in myocardium was assessed by Western blot.ResultsThe LVESD and plasma BNP concentration were significantly higher,while the LVEF and LVFS lower in the other 5 groups than in group C (P ＜0.01).No myocardial infarction was found in group S.The p-ERK1/2 expression was significantly lower in groups I/R and MP1 than in group S (P ＜ 0.05).IS and IS/AAR ratio were significantly lower,and p-ERK1/2expression was significantly higher in groups MP2.3 than in group I/R ( P ＜ 0.05).There were no significant differences in IS,IS/AAR ratio and p-ERK1/2 expression between groups MP1 and I/R (P ＞ 0.05).IS and IS/AAR ratio were decreased gradually,and the p-ERK1/2 expression was up-regulated gradually in groups MP1-3 ( P ＜0.05).ConclusionMorphine preconditioning can confer cardioprotection against myocardial I/R in a dose-dependent manner in rats with chronic heart failure.Up-regulation of p-ERK1/2 expression is involved in the underlying mechamism.

Objective To investigate the effects of remifentanil postconditioning on apoptosis in hippocampal neruons in a rat model of cerebral ischemia-reperfusion(I/R)and the mechanism involved.Methods Twentyfour male SD rats weighing 250-300 g were randomly divided into 4 groups(n = 6 each): sham operation group (group S);global cerebral I/R group(group I/R);remifentanil 0.6μg·kg- 1·min-1+global cerebral I/R group (group R1)and remifentanil 1.8μg·kg-1·min-1 + global cerebral I/R group(group R2).Global cerebral ischemia was induced by 10 min occlusion of bilateral common carotid combined with hypotension.In group R1 and R2,remifentanil at 0.6 and 1.8μg·kg-1·min-1 were infused for 5 min before ischemia respectively.The cognitive function was tested with Morris water maze and step-down tests from the day 3 to day 8 after reperfusion.When Morris water maze test was finished,rat brains were removed for HE staining and determination of the expression of caspase-3 in hippocampal CA1 region by immuno-histochemistry.Apoptosis in neurons in hippocampal CA1 region was detected by TUNEL assay.Results Compared with group S,the cognitive function was significantly decreased and the number of apopotic neurons in hippocampus CA1 region increased in group I/R,R1 and R2,and the expression of caspase-3 was up-regulated in group I/R(P＜0.05).Compared with group I/R,the cognitive function was significantly increased,the expression of caspase-3 was down-regulated,and the number of apopotic neurons in hippocampus CA1 region was significantly decreased in group R1 and R2(P＜0.05).Conclusion Remifentanil postconditioning can improve the cognitive function through down-regulating caspase-3 expression and inhibiting the apoptosis in hippocampal neruons in a rat model of cerebral I/R.

Objective To evaluate the relationship between echocardiographic epicardial adipose tissue thickness(EAT) and the presence and severity of coronary artery disease(CAD). Methods One hundredand forty-seven patients (101 patients with CAD and 46 patients with normal coronary arteries by diagnostic coronary angiography) were enrolled. EAT thickness was measured using 2-D echocardiographic parasternal long-and short-axis views. EAT thickness measurements were compared with angiographic findings. Results EAT was significantly higher in CAD group comparison to control group [(7.41 ± 1.63)mm vs (4.41±1.60) mm, P ＜0.01 ]. Furthermore, EAT increased with the severity of CAD [(8.53 ± 1.00)mm vs (6.36 ±1.73)mm, P ＜0.01]. Gensini's score significantly correlated with EAT (r = 0.71, P ＜0.01 ). EAT thickness ≥5.35 mm had 87.13% sensitivity and 80.42% specificity (ROC area 0. 89, P = 0.01,95% CI [0.84 - 0.9;]) for predicting CAD. Conclusions EAT thickness, which is easily and non-invasively evaluated by transthoracic echocardiography, can be an adjunctive marker to classical risk factors for the prediction of CAD, it was significantly correlated with the severity of coronary artery disease.