Objective To investigate the molecular biological mechanism of deposition of triglyceride(TG)in hepatocytes in alcoholic fatty liver disease(AFLD)and the pathogenesis of this condition by detecting the contents of serum tumor necrosis fac-tor-α(TNF-α),liver triglyceride(TG),peroxisome proliferator-activated receptorα(PPARα)and acyl-CoA oxidase(Acox1)mR-NAs,and liver PPARαprotein after intervention with bezafibrate,a PPARαagonist.Methods Sixty Wistar rats were randomly divided into three groups:control group(n=20),AFLD group(n=20),and bezafibrate group(n=20).Animals in control group were given distilled water by gavage once a day for 8 weeks.Those in AFLD group were given ethanol and fish oil(2.5 mL/kg) by gavage daily for the same period of time.In bezafibrate group,rats were treated by gavage with ethanol and fish oil(2.5 mL/kg)for the first 4 weeks and then with bezafibrate(100 mg/kg)for another 4 weeks.TG in the liver was measured by colorimet-ric method,serum TNF-αlevels by enzyme linked immunoabsorbent assay (ELISA),the mRNA expression of PPARαand Acox1 in hepatocytes by reverse transcription polymerase chain reaction(RT-PCR)and the expression of PPARαprotein in hep-atocytes by Western blot.Results A significant increase in TG[AFLD group(0.72±0.09)mmol/L vs.control group(0.28± 0.07)mmol/L,P<0.01]and TNF-α[AFLD group(3.01±0.31)ng/mL vs.control group(1.07±0.28)ng/mL,P<0.01]was found in AFLD group when compared with control group.After bezafibrate intervention,the contents of liver TG and serum TNF-αwere significantly decreased.The mRNA expression of PPARα[AFLD group(0.22±0.08)vs.control group(0.68± 0.13),P<0.01]and Acox1[AFLD group(0.43±0.12)vs.control group(1.14±0.21),P<0.01]was suppressed in AFLD group,which was significantly reversed by bezafibrate treatment[bezafibrate group(0.59±0.13)for PPARαmRNA vs.AFLD group,P<0.01;bezafibrate group(0.83±0.17)for Acox1 mRNA vs.AFLD group,P<0.01].The expression of PPARαpro-tein in hepatocyts was also found to decrease in AFLD group[AFLD group(0.19±0.07)vs.control group(0.48±0.11),P<0.01].After bezafibrate intervention,it was profoundly increased.Conclusion The down-expression of PPARαand Acox1 in the liver of rats with AFLD may suppress the fatty acid metabolism and lead to the TG deposition in the liver.The increase in serum TNF-αcontents also contributes to the development of AFL.Bezafibrate can prevent and treat AFL by activating PPARα,increasing the expression of PPARαand Acox1 ,promoting the metabolism of fatty acids,decreasing the TG deposition and the serum TNF-αcontents.

Objective To evaluate the role of syndecan-4 (SDC-4) in inflammatory responses of rats with ventilator-induced lung injury (VILI).Methods Twenty-four healthy male wild type Sprague-Dawley rats and 24 male SDC-4 gene knockout Sprague-Dawley rats,aged 2-3 months,weighing 200-220 g,were assigned into 2 groups (n =12 each) using a random number table:control group (group C)and VILI group.The animals were anesthetized with pentobarbital sodium and tracheostomized.The rats kept spontaneous breathing in group C.The rats were mechanically ventilated for 4 h in group VILI.Blood samples were taken from the femoral artery at the end of mechanical ventilation for detection of arterial oxygen partial pressure (PaO2).The animals were sacrificed after blood sampling.The left lung was lavaged,and the broncho-alveolar lavage fluid (BALF) was collected for determination of the tumor necrosis factor-α (TNF-α),interleukin-1beta (IL-1β) and IL-18 concentrations (by enzyme-linked immunosorbent assay) and total protein concentrations (by BCA assay).The right lungs were removed for determination of the wet to dry weight ratio (W/D ratio) and expression of TNF-α,IL-1β and IL-18 mRNA in lung tissues (by real-time polymerase chain reaction) and for examination of the pathological changes (with a light microscope).The lung injury scores were recorded.Results Compared with group C of wild type rats,PaO2 was significantly decreased,W/D ratio and lung injury scores were increased,the concentrations of total protein,TNF-α,IL-1β and IL-18 in BALF were increased,and the expression of TNF-α,IL-1β and IL-18 mRNA in lung tissues was up-regulated in group VILI of wild type rats (P＜0.05),and no significant change was found in the variables mentioned above in group C of gene knockout rats (P＞0.05).Compared with group C of gene knockout rats,PaO2 was significantly decreased,W/D ratio and lung injury scores were increased,the concentrations of total protein,TNF-α,IL-1β and IL-18 in BALF were increased,and the expression of TNF-α,IL-1β and IL-18 mRNA in lung tissues was up-regulated in group VILI of gene knockout rats (P＜0.05).Compared with group VILI of wild type rats,PaO2 was significantly decreased,W/D ratio and lung injury scores were increased,the concentrations of total protein,TNF-α,IL-1β and IL-18 in BALF were increased,and the expression of TNF-α,IL-1β and IL-18 mRNA in lung tissues was up-regulated in group VILI of gene knockout rats (P＜0.05).Conclusion SDC-4 can inhibit inflammatory responses of rats with VILI and is involved in the endogenous protective mechanism.

Objective To evaluate the role of spinal RhoA/ROCK signaling pathway in the development of lipopolysaccharide (IP)-induced inflammatory pain(IP) in rats.Methods Fifty-two male Sprague-Dawley rats, weighing 180-220 g, were equally randomized into 4 groups using a random number table: normal saline group (group NS) , LPS group, RhoA inhibitor C3 exoenzyme group (group LC) , and ROCK inhibitor Y27632 group (group LY).Inflammatory pain was induced by injecting LPS 25 μl (300 ng) into the plantar surface of hindpaws in IP, LC and LY groups, while the equal volume of normal saline was injected instead in NS group.C3 exoenzyme 10 pg and Y27632 10 nmol were injected intrathecally at 30 min prior to LPS administration in LC and LY groups, respectively.Before LPS injection (T0) , and at 1, 3, 5, 12 and 24 h after LPS injection (T1-5) , the mechanical and thermal pain thresholds were measured.Five rats in each group were sacrificed after pain thresholds were measured at T3, and L4.5 segments of the spinal cord were removed for determination of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) mRNA expression in spinal dorsal horns by real-time reverse transcriptase-polymerase chain reaction.Results Compared with group NS, the mechanical and thermal pain thresholds were significantly decreased at T2-5in IP, LC and LY groups, and TNF-α and IL-1β mRNA expression was up-regulated at T3 in IP group.Compared with group IP, the mechanical and thermal pain thresholds were significantly increased at T2-5, and TNF-α and IL-1β mRNA expression was down-regulated at T3 in LC and LY groups.Conclusion Spinal RhoA/ROCK signaling pathway is involved in the development of LPS-induced IP in rats.

Objective To evaluate the relationship between hippocampal monocyte chemotactic protein-1 (MCP-1) and its receptor C-C chemokine receptor 2 (CCR2) and postoperative cognitive dysfunction (POCD) in aged rats.Methods Forty-eight male Sprague-Dawley rats,aged 20-22 months,weighing 480-550 g,were randomly divided into 2 groups (n =24 each) using a random number table:control group (group C) and POCD group.POCD group inhaled 2.0％ isoflurane and underwent splenectomy.Before surgery and at 1,3 and 7 days after surgery,Morris water maze test was performed to evaluate the spatial learning and memory ability.The escape latency and swimming distance were recorded.Eight rats were sacrificed after the end of Morris water maze test performed at 1,3 and 7 days after surgery.Then the brains were removed,and the hippocampi were isolated for detection of the expression of MCP-1 and CCR2 by Western blot.Results Compared with group C,the escape latency and swimming distance were significantly prolonged,and the expression of MCP-1 and CCR2 in hippocampi was up-regulated at 1,3 and 7 days after surgery in POCD group.Conclusion Up-regulation of hippocampal MCP-1 and CCR2 expression may be involved in the mechanism of POCD in aged rats.

Objective To evaluate the relationship between the shedding of syndecan-4(SDC-4) in lung tissues and ventilator-induced lung injury in rats. Methods Thirty pathogen-free healthy adult male Wistar rats, weighing 220-250 g, were divided into 3 groups(n=10 each)using a random number table:control group(group C), mechanical ventilation with traditional tidal volume(VT)group(group T-VT) and mechanical ventilation with high VTgroup(group H-VT). The animals were anesthetized with pento-barbital sodium and tracheostomized. The rats kept spontaneous breathing in group C. The rats were me-chanically ventilated for 4 h with the VTset at 6 ml∕kg in group T-VT and with the VTset at 40 ml∕kg in group H-VT. Blood samples were collected immediately after the end of ventilation for measurement of serum SDC-4 concentrations by enzyme-linked immunosorbent assay. The left lung was lavaged, and broncho-alveolar lavage fluid was collected for determination of interleukin-1beta(IL-1β), IL-18, tumor necrosis factor-alpha and SDC-4 concentrations by enzyme-linked immunosorbent assay. The lungs were removed for determination of the wet to dry weight ratio and expression of SDC-4 protein and mRNA in lung tissues(by Western blot and real-time polymerase chain reaction, respectively)and for examination of the pathological changes. The lung injury scores were recorded. Results Compared with group C, the wet to dry weight ratio, lung injury scores, concentrations of IL-1β, IL-18, tumor necrosis factor-alpha and SDC-4 in bron-cho-alveolar lavage fluid and concentrations of SDC-4 in serum were significantly increased, the expression of SDC-4 mRNA was up-regulated, and the expression of SDC-4 was down-regulated in group H-VT(P<005), and no significant change was found in the parameters mentioned above in group T-VT(P>005).Marked pathological changes of lung tissues were found in group H-VT. Conclusion A large shedding of SDC-4 in lung tissues may be involved in the pathophysiological mechanism of ventilatior-induced lung injury in rats.

Objective To evaluate the efficacy of dexmedetomidine mixed with ropivacaine for thoracic paravertebral nerve blocks by multiple injections for preemptive analgesia on postoperative analgesia of patients undergoing thoracotomy. Methods Ninety patients, all genders, ASA Ⅰ or Ⅱ, aged 35-64, BMI 18-24 kg/m2, undergoing radical operation for esophageal carcinoma were randomly divided into three groups (each group 30 patients): group C received general anesthesia, group R received ropivacaine for thoracic paravertebral nerve block and group RD received dexmedetomidine mixed with ropivacaine for thoracic paravertebral nerve block.Three groups all used intravenous infusion of propofol, refentanyl and inhalation sevoflurane for anesthesia maintenance, and PCIA pump started before the end of surgery in 3 groups.Meanwhile, group R and group RD received ultrasound-guided T4-T8thoracic paravertebral nerve blocks by multiple injections on operation side preoperatively.In group R, the mixture of 0.5% ropivacaine 19 ml and 1ml of normal saline was injected, and in group RD, the mixture of dexmedetomidine 1 μg/kg and 19 ml of 0.5% ropivacaine was injected.The analgesia process lasted 48 h after surgery of these 3 groups, and the VAS score was maintained<4 points.When the VAS score was 4 or more points, intravenous injection of morphine 5- 10 mg was delivered. Postoperative PCIA liquid and morphine consumption, somnolence, nausea, vomiting, respiratory depression, itching and urinary retention was recorded. Additionally, the occurrences of adverse events about thoracic paravertebral nerve blocks were recorded.Results The dosages of propofol, refentanyl in group R and group RD were lower than those in group G:(7.2 ± 0.6),(6.1 ± 0.5)mg/(kg·h)vs.(8.1 ± 0.5)mg/(kg·h), and there were significant differences(P<0.05).The dosage of propofol in group RD was lower than that in group R: (6.1 ± 0.5) mg/(kg·h) vs. (7.2 ± 0.6) mg/(kg·h), and there was significant difference (P <0.05). Compared with group G, the consumption of PCIA liqud and the usage rate of morphine was reduced in group R and group RD (P < 0.05); the consumption of PCIA liqud and the usage rate of morphine was lower in group RD than that in group R(P<0.05).The rate of nausea and vomiting and itch in group R and group RD was lower than that in group G,and there were significant differences(P<0.05). No significant difference in somnolence showed between three groups (P > 0.05). Conclusions Ropivacaine combined with dexmedetomidine for target thoracic paravertebral nerve blocks by multiple injections for preemptive analgesia can significantly improve the efficacy of postoperative analgesia after thoracotomy, meanwhile,it can also save the dosage of anesthetic drugs during the operation.

Objective: To evaluate the role of microRNA-125b (miR-125b) on ventilator-induced lung injury (VILI) in mice. Methods: Forty healthy male C57BL/6 male mice, weighing 25-30 g, aged 2-3 months, were divided into 4 groups (n=10 each) using a random number table method: sham operation group (group Sham), group VILI, VILI plus miR-125b negative control group (group VILI+ NC), and VILI plus miR-125b overexpression group (group VILI+ miR-125b agomir). In VILI+ NC and VILI+ miR-125b agomir groups, miR-125b negative control and miR-125b agomir transfection complex 50 μl were intratracheally instilled, respectively, and 48 h later VILI model was established.The animals were mechanically ventilated for 4 h with high tidal volume (40 ml/kg) to induce VILI.Blood samples were obtained from the femoral artery at 4 h of mechanical ventilation for detection of PaO₂, then animals were sacrificed, lungs were removed for determination of wet to dry weight ratio (W/D ratio) and for examination of pathological changes (with a light microscope), and lung injury was scored.In VILI+ NC and VILI+ miR-125b agomir groups, bronchoalveolar lavage fluid (BALF) was collected to measure the concentrations of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) by enzyme-linked immunosorbent assay.The cell apoptosis of lung tissues was measured using TUNEL, apoptosis index was calculated, the caspase-3 expression was detected by Western blot, and the miR-125b expression was detected by real-time polymerase chain reaction. Results: Compared with Sham group, PaO₂ was significantly decreased, and W/D ratio and lung injury score were increased in VILI, VILI+ NC and VILI+ miR-125b agomir groups, and the expression of miR-125b was down-regulated in VILI and VILI+ NC groups (P<0.05). Compared with VILI group, PaO₂ was significantly increased, W/D ratio and lung injury score were decreased, the expression of miR-125b was up-regulated (P<0.05), the pathological changes of lung tissues were significantly attenuated in group VILI+ miR-125b agomir, and no significant change was found in the parameters mentioned above in group VILI+ NC (P<0.05). Compared with group VILI+ NC, the concentrations of TNF-α and IL-6 in BALF and apoptotic index were significantly decreased, and the expression of caspase-3 was down regulated in group VILI+ miR-125b agomir (P<0.05). Conclusion MiR-125b is involved in the endogenous protective mechanism of VILI in mice.

Objective:To evaluate the effect of individualized positive end-expiratory pressure (PEEP) titration based on open-lung strategy on the intraoperative thoracic fluid content (TFC) in elderly patients undergoing transurethral ultrasound-guided laser-induced prostatectomy (TULIP).Methods:Eighty-six American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, patients, aged 65-80 yr, with body mass index of 18-28 kg/m 2, scheduled for elective TULIP, were divided into 2 groups ( n=43 each) by the random number table method: fixed PEEP group (group C) and individualized PEEP titration group (group P). PEEP was set at 4 cmH 2O after routine mechanical ventilation in group C. Patients underwent pulmonary recruitment maneuvers combined with individualized PEEP titration during surgery in group P. TFC was measured using a non-invasive cardiac output monitor at 5 min after tracheal intubation (T 0), 30 min after PEEP titration and ventilation (T 1), 5 min before surgery (T 2), and 5 min before leaving the recovery room (T 3). Cardiac output, oxygenation index and stroke volume index were recorded from T 0-T 2, arterial blood gas analysis was simultaneously performed to record peak airway pressure and dynamic lung compliance, and oxygenation index was calculated. The duration of postanesthesia care unit stay, pulmonary complications within 7 days after surgery, and length of hospital stay were also recorded. Results:Eighty-three patients were finally included, with 42 in group C and 41 in group P. Compared with group C, TFC was significantly decreased at T 1-T 3, cardiac index, cardiac output and stroke volume index were decreased at T 1, dynamic lung compliance, PaO 2 and oxygenation index were increased at T 1 and T 2, PaCO 2 was decreased, the incidence of postoperative pulmonary complications was reduced, and the duration of postanesthesia care unit stay and postoperative length of hospital stay were shortened in group P ( P<0.05). Conclusions:Individualized PEEP titration based on open-lung strategy can effectively decrease TFC and improve intraoperative oxygenation and prognosis in elderly patients undergoing TULIP.