Objective To investigate the role of gamma-aminobutyric acid (GABA) A receptor (GABAAR) in lung tissues in lipopolysaccharide (LPS)-induced acute lung injury in rats.Methods Thirty-two male Wistar rats,aged 8 weeks,weighing 200-230 g,were randomly divided into 4 groups (n =8 each) ∶ control group (group C),group LPS,GABA pretreatment + LPS group (group GABA) and GABAAR antagonist bicuculline pretreatment + LPS group (group BIC).Acute lung injury was induced by intravenous LPS 5 mg/kg in groups LPS,GABA and BIC,while the equal volume of normal saline was given in group C.GABA 50 mg/kg and bicuculline 10 μmol/kg were injected intraperitoneally 30 min before LPS injection in GABA and BIC groups,respectively.Arterial blood samples were collected at 6 h after LPS injection for measurement of arterial partial pressure of oxygen (PaO2).The animals were then sacrificed and lungs removed for determination of W/D lung weight ratio,GABAAR expression,contents of interleukin-6 (IL-6),tumor necrosis factor-α (TNF-α) and malondialdehyde (MDA) and superoxide dismutase (SOD) activity in lung tissues and for microscopic examination.Results Compared with group C,PaO2 was significantly decreased in the other three groups,and W/D lung weight ratio,TNF-α,IL-6 and MDA contents were significantly increased,GABAAR expression was up-regulated,and SOD activity was decreased in groups LPS and GABA (P ＜ 0.05).Compared with group LPS,W/D lung weight ratio,TNF-α,IL-6 and MDA contents were significantly increased,GABAAR expression was up-regulated,and SOD activity was decreased in group GABA (P ＜ 0.05),and no significant change was found in the parameters mentioned above in group BIC and in PaO2 in groups GABA and BIC (P ＞ 0.05).Conclusion GABAA R in lung tissues is involved in the development of acute lung injury induced by LPS.

BACKGROUND: The abnormal apoptosis of intestinal epithelial cells is the main cause of intestinal mucous membrane injury during ischemia reperfusion. Shenfu injection has good therapeutic effect on intestinal mucous membrane injury. OBJECTIVE: To investigate the influence of shenfu injection medication on intestinal apoptotic epithelial number, apoptosis-related caspase-3 and Bcl-2 gene expression, as well as the level of tumor necrosis factor (TNF)in intestinal ischemia reperfusion rat model.DESIGN: Randomized controlled experiment.SETTING:Department of Anesthesia, Renmin Hospital of Wuhan University.MATERIALS:This experiment was carried out in the laboratory of the Department of Anesthesia, Renmin Hospital of Wuhan University, between December 2002 and June 2003. Totally 24 healthy SD rats of clean grade were randomized into blank control group, intestinal ischemia reperfusion (IR) group and shenfu injection group with 8 rats in each group.METHODS: Rats in each group were anesthetized with intraperitoneal injection of ethyl carbamate at dosage of 1mg/kg; then in intestinal IR group and shenfu injection group rats' superior mesenteric artery was occluded with vascular clamp for 1 hour before 2-hour reperfusion,which was not conducted in blank control group. Rats in shenfu injection group were intravenously injected with shenfu injection at 30 minutes before occlusion at dose of 0.02 mL/g, which was replaced by the same volume of physical saline in blank control group and intestinal IR group. The expression of caspase-3 and Bcl-2 protein and cell apoptosis wee detected.MAIN OUTCOME MEASURES: ① Comparison of apoptotic index between groups. ② The expression of caspase-3 and Bcl-2 gene in rat intestinal epithelium. ③ Comparison of TNF content in intestinal mucous membrane homogenate between groups.RESULTS: Totally 24 rats were included in this experiment and all ehtered the result analysis. ①Comparison of apoptotic index between groups:The apoptotic index was obviously lower in shenfu injection group than in intestinal IR group, but higher than in blank control group [(7.75-±1.89)%,(28.25±8.50)%, (4.25-±2.63)%, P ＜ 0.01]. ② The expression of caspase-3 and Bcl-2 gene in rat intestinal epithelium: caspase-3 expression was lower in shenfu injection group than in intestinal IR group, but higher than in blank control group [(0.211 6±0.087 5), (0.354 7±0.077 8), (0.194 1±0.057 4) A,P ＜ 0.01, P ＞ 0.05]; Bcl-2 expression was remarkably higher in intestinal IR group than in blank control group (P ＜ 0.05), but obviously reduced in shenfu injection group compared to intestinal IR group (P ＜ 0.01). ③ TNF content of intestinal mucous membranehomogenate in each group: TNF content was remarkably higher in intestinal IR group than in blank control group and shenfu injection group [(189.7±56.3), (38.6±10.4), (47.5±l8.7)mg/L,P ＜ 0.01], and basically the same in shenfu inj~tion group and blank control group (P ＞ 0.05).CONCLUSION: Shenfu injection can suppress intestinal epithelial apoptosis by reducing TNF content and caspase-3 e.pression as well as upregulating the expression of Bcl-2 gene during ischemia reperfusion, thereby attenuating ischemia reperfusion injury of intestinal mucous membrane.

Objective To establish neuropathic pain models,explore the effects and mechanisms of dexmedetomidine on neuropathic pain.Methods Wistar rats were randomly divided into four groups (n =9):0.9％ sodium chloride solution CCI group (N),dexmedetomidine CCI group (D),ZD7288 CCI group (Z) and sham-operated group (Sham).Sciatic nerve ligation was performed in group N,D and Z.The sciatic nerve in group Sham was exposured without ligation.7 d after surgery,the rats in group D were intraperitoneal injected with dexmedetomidine (40 μg· kg-1),and the rats in group Z were intraperitoneal injected with ZD7288 (10 mg·kg-1)once a day for 3 d.The same volume of 0.9％ sodium chloride solution was given at the same time in group N.The behavioral test was performed before and 7 d after operation,as well as 3 d after injection treatment.Mechanical allodynia was assessed by paw withdrawal mechanical threshold (PWMT) to von Frey filaments.Thermal hyperalgesia was assessed by paw thermal withdrawal latency (TWL) to radiant heat.Dexmedetomidine block of HCN channels in dorsal root ganglion (DRG) neurons were confirmed by whole-cell recording.Results 7 d after surgery,the PWMT and TWL of rats in group N,D and Z were decreased significantly (P ＜ 0.05).The PWMT and TWL in group Sham were no significant difference before and after operation.Dexmedetomidine significantly increased the levers of PWMT and TWL in group D and Z after treatment for 3 d,and group Z was greater than group D (P ＜ 0.05).Dexmedetomidine (0.1,1,10 μmol· L-1) caused a concentration-dependent decrease in the amplitude of Ih in DRG neurons from (-844.43 ± 386.34) to (-215.99 ± 63.90) pA (P ＜ 0.05),and the inhibition rate of Ih was (11.87 ± 1.80) ％,(35.26 ± 3.65) ％ and (52.02 ± 5.56) ％,respectively(P ＜0.05).Dexmedetomidine produced a dose-related shift to the left of the Ih activation,and a negative shift in V1/2 (P ＜ 0.05).V1/2 shifted from (-86.21 ± 1.68) to (-103.54 ± 2.01) mV (P ＜ 0.05).The slope values were not altered by dexmedetomidine.Conclusion Dexmedetomidine produces a dose-dependently analgesic effect on neuropathic pain after peripheral never injury,which is likely due to the inhibition of Ih and reduction of ectopic spontaneous discharge in DRG neurons.

0.05)]. Conclusion The elevated serum HA is linked to a potential marker in kidney transplantation.

Objective To compare the roles of inflammatory response in acute lung injury (ALI) induced by blunt chest trauma verus by blunt chest trauma-hemorrhagic shock and resuscitation (double hits) in rats.Methods Thirty male Sprague-Dawley rats,aged 8 weeks,weighing 240-280 g,were randomly assigned into 3 equal groups (n =10 each) using a random number table:sham operation group (S group),blunt chest trauma group (T group),and blunt chest trauma and hemorrhagic shock and resuscitation group (THSR group).Lung contusion was induced in anesthetized rats by dropping a 300 g weight onto a precordial protective shield to direct the impact force away from the heart and toward the lungs.Blood was withdrawn via the left femoral artery 5 min later until MAP was decreased to 35-45 mmHg within 15 min and maintained at this level for 60 min,followed by resuscitation.At 6 h after the model was established,the arterial blood samples were collected for blood gas analysis and detection of serum concentrations of tumor necrosis factor-α (TNF-α),interleukin-6 (IL-6),IL-1β and IL-10 (by ELISA).The rats were then sacrificed and pulmonary specimens were obtained for determination of contents of TNF-α,IL-6,IL-1β and IL-10 in lung tissues and for microscopic examination.Results Compared with group S,PaO2 was significantly decreased,and the levels of TNF-α,IL-6,IL-1β and IL-10 in serum and lung tissues were increased in T and THSR groups.Compared with group T,PaO2 was significantly decreased,and the levels of TNF-α,IL-6,IL-1β and IL-10 in serum and lung tissues were increased in group THSR.The histopathological damage to lung tissues was aggravated in THSR group as compared with T group.Conclusion The role of inflammatory response in ALI induced by blunt chest trauma-hemorrhagic shock and resuscitation (double hits) is significantly stronger than that in ALI induced by blunt chest trauma alone in rats.

Objective To investigate the effect of ischemic post-conditioning (IPO) on the level of Heme oxygenase-1 (HO-1) in acute ischemia - reperfusion (I/R) injury of lung in order to illuminate its protective mechanism.Methods Forty-eight adult SD rats were randomly divided (random number) into 6groups ( n =8 each):sham operation group ( S group) ; I/R group in which the hilum of left lung was clamped for 45 min followed by 105 min reperfusion; IPO group in which left lung hilum was clamped for 45min and post - conditioned by alternation of 30 s reperfusion with 30 s re-occlusion for three times before perfect perfusion for 102 min; Hemin (HM) + I/R group; ZnPPⅨ (zinc protoporphyrin Ⅸ) + IPO group and HM + S group.Arterial partial pressure of oxygen ( PaO2 ) and malondialdehyde (MDA) content in blood serum were assayed.The left lung was removed for determination of wet/dry (W/D) lung weight ratio and level of HO-1 protein was detected by immunohistochemical technique and pathohistological changes were observed under light microscopic examination. Comparisons among multiple groups were studied by using one-way analysis of variance (ANOVA). Statistical comparisons within groups were analyzed by using paired t -test.Results The level of HO-1 in lung tissue was significantly increased in the I/R group compared with the S group and the HM + S group (P ＜0.01,P ＜0.05).Compared to the I/R group,the IPO and the HM + I/R groups had significant higher level of HO-1 ( P ＜ 0.05,P ＜ 0.01 ).The PaO2 was significantly lower in all experimental groups than that in the S group (90 ± 11 ) mmHg.However,the values of PaO2 in the IPO and the HM + I/R groups were higher than that in the I/R group (P ＜ 0.01 ).In addition to severe lung tissue damage evidenced by pathohistological changes,the lung wet/dry (W/D) weight ratio and MDA level in blood serum were significantly higher in the I/R group than those in the S group (P ＜0.01 ),whereas the lung damage was attenuated either by IPO or by HM pretreatment (P ＜ 0.05,IPO or HM + I/R vs.I/R).Conclusions IPO can attenuate the lung ischemia - reperfusion injury through upregulating the level of HO-1 protein and inhibiting lipid peroxidation injury.

Objective To investigatc the role of phosphatidylinositol 3-kinase (PI3K)/protein-serine-threonine kinases (Akt) signal pathway in ginsenoside Rb1 pretreatment-induced attenuation of myocardial ischemiareperfusion (I/R) injury in diabetic rats.Methods Male SD rats weighing 250-300 g were used in this study.Diabetes mellitus was induced by intraperitoneal streptozotocin and confirmed by fasting blood glucose ≥ 16.7mmol/L.Eight weeks after diabetes mellitus was induced,48 rats were randomly divided into 4 groups ( n =12each):group myocardial I/R (group I/R); group ginsenoside Rb1 (group R); group ginsenoside Rb1 + wortmannin (PI3K inhibitor) (group RW) and group wortmannin (group W).Myocardial I/R was induced by occlusion of anterior descending branch of left coronary artery for 30 min followed by 120 min reperfusion.Ginsenoside Rb1 40 mg/kg was injected iv at 10 min before ischemia in groups R and RW,while in groups RW and W wortmannin 15 μg/kg was injected iv at 20 min before ischemia.Arterial blood samples were collected at the end of 120 min reperfusion for determination of creatine kinase (CK) and lactate dehydrogenase (LDH) activities.The rats were then sacrificed.The infarct size was measured by tetrazolium method.Myocardial apoptosis was detected by TUNEL and apoptotic index (the number of apoptotic myocardial cells/the total number of myocardial cells) was calculated.The expression of Akt and phosphorylated Akt (p-Akt) was determined by Western blotting.Results Ginsenoside Rb1 pretreatment significantly reduced the infarct size,myocardial cell apoptotic index and serum CK and LDH activities and up-regulated p-Akt expression in group R as compared with group I/R.The protective effects of ginsenoside Rbl against myocardial I/R injury were significantly attenuated by wortmannin pretreatment in group RW compared with group R.Conclusion PI3K/Akt signal pathway is involved in the protective effects of ginsenoside Rb1 against myocardial I/R injury in diabetic rats.

Objective To explore method of early diagnosis and treatment of adult patients with cerebral ischemic stroke after cardiovascular surgery.Methods The chnical data of 24 adult patients with cerebral ischemic stroke after cardiovascular surgery were retrospectively analyzed.Firstly,CT or MRI should be accomplished to determine the type of cerebral ischemic stroke as soon as patients' condition of circulation and respiration were stable.Secondly,the vital signs should be monitored closely,and the consciousness,pupil,respiratory and hmbs activity of the patients were observed.Thirdly,the patients' temperature of head should be reduced and be given dehydration,anticoagulation,cholesterol-lowering medication,brain nutrition drugs,beta receptor blockers and other drugs.Overall,the balance of fluid,electrolytes and acid-base were maintained in the course of treatment.Results Among the 24 patients,male was 66.7％ (16/24).Early cerebral ischemic stroke occurred in 6 cases,delayed cerebral ischemic stroke occurred in 18 cases.Cerebral ischemic stroke happened in 12 patients who underwent coronary artery bypass grafting surgery,8 patients after cardiac valve replacement surgery,2 cases after artery dissection surgery and 2 patients after other surgery.Two cases were death during hospital stay,the mortality was 8.3％ (2/24).Conclusion Adult patients with clinical manifestation of cerebral ischemic stroke after cardiovascular surgery should be diagnosed early as soon as possible,the treatment key of cerebral ischemic stroke is strict monitoring and comprehensive treatment.

Objective To investigate the effect of ischemic postconditioning (IPO) on renal injury induced by intestinal ischemia-reperfusion (I/R) and the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) in mice.Methods Thirty-six healthy male C57BL/6J mice,aged 9-12 weeks,were randomly divided into 3 groups ( n =12 each):sham operation group ( S group),I/R group,and IPO + I/R group ( group IPO).Intestinal I/R was produced by occlusion of superior mesenteric artery for 45 min followed by 2 h reperfusion.The mice underwent 3 cycles of 30 s reperfusion and 30 s ischemia at the end of 45 min ischemia before 2 h reperfusion.Blood samples were collected from carotid artery at 2 h of reperfusion and then the mice were sacrificed.The kidney was removed for microscopic examination.The pathological changes of the kidney were scored.The concentrations of serum blood urea nitrogen (BUN),creatinine (Cr) and neutrophil gelatinase-associated lipocalin (NGAL)were detected.The expression of Nrf2 and heme oxygenase- 1 ( HO- 1 ),superoxide dismutase (SOD) activity,and the content of malondialdehyde (MDA),TNF-α,IL-6 and IL-10 were determined in renal tissues.Results The concentrations of serum BUN,Cr and NGAL,MDA content and the expression of Nrf2 and HO- 1 were significantly higher,SOD activity was significantly lower,and the pathological score was significantly higher in group I/R that in group S ( P ＜ 0.05).The concentrations of serum BUN,Cr and NGAL and MDA content were significantly lower,the expression of Nrf2 and HO-1 and SOD activity were significantly higher,and the pathological score was significantly lower in group IPO that in group I/R ( P ＜0.05).There was no significant difference in the content of TNF-αα,IL-6 and IL-10 among all groups(P＞0.05).Conclusion IPO can alleviate the renal injury induced by intestinal I/R through promoting the expression of Nrf2 and up-regulating the expression of HO-1 in mice.

BACKGROUND:The treatment of pulmonary hypertension secondary to congenital heart disease has been a hot topic in the clinical research on cardiac surgery. Although traditional drugs for reducing pulmonary hypertension have excelent effects, there are some defaults, such as difficult monitoring and rebounding phenomenon after drug withdrawal. The traditional heart dacron graft is prone to cause complications, such as deformation, thrombosis, embolism, hemolysis and infection. OBJECTIVE:To investigate the effect of glutaraldehyde-fixed bovine pericardium patch and aerosolized iloprost in patients with pulmonary hypertension secondary to congenital heart disease. METHODS:Ninety patients with pulmonary hypertension due to congenital heart disease underwent a surgery. Glutaraldehyde-treated bovine pericardium patch were used to repair cardiac septal defect, and then aerosolized iloprost was applied after operation, administered for 3 days according to 30 ng/min/kg, every 4 hours in the first 12 hours of a day, and every 6 hours in the resting 12 hours. Mean arterial pressure, mean pulmonary arterial pressure, systemic vascular resistance index, pulmonary vascular resistance index were recorded before inhalation, immediately after inhalation, and 30 minutes after inhalation. The pericardium-associated complications, and cardiac function were also observed at folow-ups. RESULTS AND CONCLUSION: The involved 90 cases were detected by echocardiography. The results showed that, al the flaps were closed, there was no shunting or echo discontinuation of atrial septum. The heart contraction function was normal. No pericardium-associated complications were found. There was no significant difference in the mean arterial pressure and systemic vascular resistance index in al patients at different time points. The mean pulmonary arterial pressure and pulmonary vascular resistance index immediately after inhalation were significantly lower than that before inhalation (P < 0.01). The decrease was also significant 30 minutes after inhalation (P < 0.05). The intervention of glutaraldehyde-fixed bovine pericardium patch and aerosolized iloprost is safe and effective to treat patients with pulmonary hypertension secondary to congenital heart disease.