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Objective:To design a modified S1PR3 specific agonist, GPS-725.017, and investigate its protective effect on acute lung injury by promoting macrophage clearance of bacteria.Methods:A short peptide derived from the intracellular region of S1PR3 receptor was named GPS725.017, which was modified with norleucine (Nle) and myristicacid (myr) at its N terminus. Mice were divided into the sham operation group, solvent group and GPS-725.017 treatment group. The acute lung injury model was induced by endotracheal injection of E. coli (5×10 6 CFU), and the experimental group was treated with GPS-725.017 (10 mg/kg). The 48-h survival rate of mice was recorded. After 5 h of modeling, the bacterial load and inflammatory cytokines in peripheral blood and lung were detected, and Vps34 protein content in alveolar macrophages was determined by Western blot. After 12-h of modeling, lung tissues were collected for H&E staining and pathological scores. Results:Compared with the solvent group, the survival rate of mice in the GPS-725.017 treatment group was significantly improved ( P<0.01), the bacterial CFU in blood and alveolar lavage fluid was significantly lower than that in the solvent group ( P<0.001), and the levels of TNF-α and IL-1β in blood and alveolar lavage fluid were significantly lower than those in the solvent group ( P<0.001). Western blot showed that the expression level of Vps34 protein in alveolar macrophages was significantly higher than that in the solvent group ( P<0.01). Histopathology result showed that the pathological damage of lung in the treatment group was significantly less than that in the solvent group ( P<0.001). Conclusions:The modified synthetic S1PR3 specific agonist GPS-725.017 could specifically activate the S1PR3 receptor on the membrane of alveolar macrophages and up-regulate the expression level of intracellular Vps34 protein, which can promote the removal of bacteria in alveolar macrophages, significantly reduce the degree of lung injury and improve the survival rate in ALI mice.
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Objective:To evaluate the role of mitophagy in cognitive dysfunction in rats with sepsis-associated encephalopathy (SAE).Methods:Twenty-four clean-grade healthy male Sprague-Dawley rats, aged 13-14 weeks, weighing 230-250 g, were divided into 3 groups ( n=8 each) using a random number table method: sham operation group (Sham group), SAE group and SAE+ autophagy inhibitor 3-methyladenine (3-MA) group (3-MA group).The SAE models were developed by cecal ligation and puncture in anesthetized animals.3-MA 10 mg/kg was intraperitoneally injected at 30 min after developing the model in 3-MA group.Cognitive function was assessed by Morris water maze test, and the escape latency and ratio of the time of staying at the target quadrant were recorded.After the end of Morris water maze test, the rats were sacrificed and hippocampal tissues were collected for microscopic examination of the pathological changes which were scored after hematoxylin-eosin staining and for determination of the expression of autophagy-related proteins LC3, Beclin1 and p62 (by Western blot).The ratio of LC3Ⅱ/LC3Ⅰwas calculated.The hippocampal mitochondria were isolated to measure mitochondrial membrane potential (MMP), ATP content and ATPase activity by spectrophotometry. Results:Compared with Sham group, the escape latency was significantly prolonged, the ratio of the time of staying at the target quadrant was decreased, the pathological score of hippocampus was decreased, and the contents of MMP and ATP and ATPase activity were decreased in SAE and 3-MA groups, the ratio of LC3Ⅱ/LC3Ⅰwas significantly increased, the expression of Beclin1 was up-regulated, and the expression of p62 was down-regulated in SAE group, and the ratio of LC3Ⅱ/LC3Ⅰwas significantly decreased, and the expression of Beclin1 and p62 was up-regulated in 3-MA group ( P<0.05).Compared with SAE group, the escape latency was significantly prolonged, the ratio of the time of staying at the target quadrant was decreased, the pathological score of hippocampus was decreased, the ratio of LC3/LC3Ⅰwas decreased, the expression of Beclin1 was down-regulated, the expression of p62 was up-regulated, and the contents of MMP and ATP and ATPase activity were decreased in 3-MA group ( P<0.05). Conclusions:Hippocampal mitophagy is involved in cognitive dysfunction in the rats with SAE.
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Objective:To evaluate the relationship between early postoperative recovery and frailty after digestive endoscopy-assisted minimally invasive surgery under intravenous anesthesia in the elderly.Methods:This study retrospectively selected hospitalized patients, aged ≥65 yr, scheduled for elective gastrointestinal endoscopic treatment.Early postoperative recovery time was defined as the period from the end of propofol administration to the achievement of a modified Aldrete score of 9.All the patients were divided into 2 groups according to whether the early recovery time after operation was less than 75%: normal early postoperative recovery time group and delayed early postoperative recovery time group.Frailty was assessed using the frailty phenotype (FP score 0-5), and the patient was diagnosed as frail (FP ≥3) or non-frail (FP 0-2). The age, sex, height, weight, smoking history, American Society of Anesthesiologists (ASA) Physical Status classification, type of operation, and baseline mean arterial pressure and heart rate were recorded.Logistic regression analysis was used to identify the risk factors for delayed early postoperative recovery time after minimally invasive digestive endoscopy under intravenous anesthesia in elderly patients.Results:A total of 214 patients were enrolled and divided into normal early postoperative recovery time group ( n=169) and delayed early postoperative recovery time group ( n=45). There were significant differences in frailty, age, drinking history of more than 10 yr, preoperative ASA Physical Status classification and propofol administration time between delayed early postoperative recovery time group and normal early postoperative recovery time group ( P<0.05). The results of logistic regression analysis indicated that frailty, age, ASA Physical Status classification Ⅲ, and propofol administration time were independent risk factors for the occurrence of delayed early postoperative recovery ( P<0.05). Conclusions:Frailty, age, ASA Physical Status classification Ⅲ and propofol administration time are independent risk factors for delayed early postoperative recovery time following digestive endoscopy-assisted minimally invasive surgery under intravenous anesthesia in elderly patients.
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Objective:To evaluate the role of p38 mitogen-activated protein kinase (MAPK)/cyclic adenosine monophosphate response element-binding protein (CREB) signaling pathway in tetramethylpyrazine-induced reduction of hippocampal inflammatory responses in mice with sepsis-associated encephalopathy (SAE).Methods:Sixty healthy male C57BL6 mice, weighing 24-27 g, were divided into 4 groups ( n=15 each) using a random number table method: sham operation group (group Sham), sepsis group (group Sep), tetramethylpyrazine group (group TMP) and p38 MAPK inhibitor SB203580 group (group SB). The model of SAE was established by cecal ligation and puncture in anesthetized mice.Tetramethylpyrazine 10 mg/kg was injected intraperitoneally once a day at 3 days before the establishment of the model in TMP group, and SB203580 2.0 mg/kg was intraperitoneally injected at 30 min after the establishment of the model in SB group.The equal volume of normal saline was given intraperitoneally in Sham and Sep groups.At 1 day after operation, cognitive function was assessed by Morris water maze, and the escape latency and ratio of time spent in the target quadrant were recorded.The animals were sacrificed after the test, and hippocampal tissues were taken for determination of the contents of interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and IL-6 (by enzyme-linked immunosorbent assay) and for detection of the expression of phosphorylation of p38 MAPK, GSK3 and CREB and expression of brain-derived neurotrophic factor (BDNF) (by Western blot). Results:Compared with group Sham, the escape latency was significantly prolonged, the ratios of time spent in the target quadrant were decreased, the contents of IL-1β, TNF-α and IL-6 were increased, the phosphorylation of hippocampus p38 MAPK was increased, the phosphorylation of GSK3 and CREB were decreased, and the expression of BDNF was down-regulated in Sep, TMP and SB groups ( P<0.05). Compared with group Sep, the escape latency was significantly shortened, the ratios of time spent in the target quadrant were increased, the contents of IL-1β, TNF-α and IL-6 were decreased, the phosphorylation of hippocampus p38 MAPK was decreased, the phosphorylation of GSK3 and CREB were increased, and the expression of BDNF was up-regulated in TMP and SB groups ( P<0.05). Compared with group TMP, no significant change was found in the parameters mentioned above in group SB ( P>0.05). Conclusion:p38 MAPK/CREB signaling pathway is involved in the process of tetramethylpyrazine-induced reduction of hippocampal inflammatory responses in mice with SAE.
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Objective:To evaluate the effect of tetramethylpyrazine on hippocampal inflammatory responses in rats with sepsis-associated encephalopathy.Methods:Sixty healthy male Sprague-Dawley rats, aged 12-14 weeks, weighing 240-270 g, were divided into 4 groups ( n=15 each) using a random number table method: sham operation group (group Sham), sepsis-associated encephalopathy group (group SAE), low-dose tetramethylpyrazine group (group L-TMP), and high-dose tetramethylpyrazine group (group H-TMP). Sepsis-associated encephalopathy was induced by cecal ligation and puncture (CLP) in anesthetized rats.Tetramethylpyrazine 5 and 20 mg/kg were intraperitoneally injected once a day in L-TMP and H-TMP groups, respectively, at 5 days prior to CLP.Morris water maze test was performed at 1-5 days after CLP to assess the cognitive function, and the escape latency and ratio of time spent in the target quadrant were recorded.Five rats were sacrificed at 1 day after CLP, the brains were removed, and the hippocampi were isolated for determination of the contents of interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α) and IL-6 by enzyme-linked immunosorbent assay.Rats were sacrificed after the end of Morris water maze test, and hippocampi were removed for detection of the expression of Toll-like receptor 1 (TLR1), activated caspase-3, Bax and Bcl-2 by using Western blot. Results:Compared with group Sham, the escape latency was significantly prolonged, the ratios of time spent in the target quadrant were decreased, the expression of TLR1, activated caspase-3 and Bax was up-regulated, and the expression of Bcl-2 was down-regulated in group SAE, group L-TMP and group H-TMP, and the contents of IL-1β, TNF-α and IL-6 were significantly increased in group SAE and group L-TMP ( P<0.05). Compared with group SAE, the escape latency was significantly shortened, the ratio of time spent in the target quadrant was increased, the contents of IL-1β, TNF-α and IL-6 were decreased, the expression of TLR1, activated caspase-3 and Bax was down-regulated, and the expression of Bcl-2 was up-regulated in group L-TMP and group H-TMP ( P<0.05). Conclusion:The mechanism by which tetramethylpyrazine reduces sepsis-associated encephalopathy may be related to inhibiting hippocampal inflammatory responses in rats.
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Objective To evaluate the effect of transversus abdominis plane (TAP) block on postoperative cognitive function in elderly patients undergoing laparoscopic surgery under general anesthesia.Methods Forty-eight male patients undergoing laparoscopic tension-free repair of inguinal hernia under general anesthesia,aged 65-75 yr,of American Society of Anesthesiologists physical status Ⅱ or Ⅲ,with body mass index of 20-28 kg/m2,were divided into 2 groups (n =24 each) using a random number table method:TAP block combined with general anesthesia group (group TG) and general anesthesia group (group G).Anesthesia was induced with midazolam,cisatracurium besylate,sufentanil and etomidate,and the patients were mechanically ventilated after laryngeal mask airway insertion.TAP block was performed through the anterior superior iliac spine approach,and 0.25％ ropivacaine 30 ml was injected in group TG.Anesthesia was maintained by target-controlled infusion of propofol and remifentanil and muscle relaxation by intravenously injecting cisatracurium.The occurrence of cerebral regional oxygen saturation (rSO2) and low rSO2 events (rSO2 ＜60％) was recorded at 1 min before anesthesia induction (T0),5 min after inserting the laryngeal mask airway (T1),at skin incision (T2),30 min after skin incision (T3),and at the end of surgery (T4).The consumption of propofol and remifentanil was recorded during surgery.Montreal Cognitive Assessment (MoCA) was used to evaluate the cognitive function of patients at 1 day before surgery and 7 days after surgery,and the development of postoperative cognitive dysfunction (POCD,MoCA scores＜ 26) was recorded.Results Compared with group G,the intraoperative consumption of propofol and remifentanil was significantly reduced,rSO2 was increased at T2~,and the incidence of low rSO2 events was decreased,MoCA scores were increased at 7 days after surgery,and the incidence of POCD was decreased in group TG (P＜0.05).Conclusion TAP block can reduce the incidence of POCD in elderly patients undergoing laparoscopic surgery under general anesthesia.
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Objective To evaluate the effect of tetramethylpyrazine on autophagy in the hippocam-pal neurons of rats with sepsis-associated encephalopathy. Methods Sixty SPF healthy male Sprague-Daw-ley rats, aged 11-14 weeks, weighing 200-240 g, were divided into 3 groups(n=20 each)using a ran-dom number table: sham operation group(group Sham), sepsis group(group Sep)and tetrameth-ylpyrazine group(group TMP). Sepsis was induced by cecal ligation and puncture(CLP), and group Sham only underwent simple laparotomy. Tetramethylpyrazine 10 mg∕kg was injected intraperitoneally at 1 h before CLP in group TMP. Morris water maze test was performed in 10 rats randomly selected at 12 and 36 h after CLP. Then the rats were sacrificed, and hippocampi were isolated for determination of the expres-sion of microtubule-associated protein 1 light chain 3Ⅰ(LC3Ⅰ), LC3Ⅱ, Beclin-1 and p62 in hipp-ocampal tissues by Western blot, and the LC3Ⅱ∕LC3Ⅰratio was calculated. Results Compared with group Sham, the escape latency was significantly prolonged, the rate of time spent in the target quadrant was decreased, the LC3Ⅱ∕LC3Ⅰratio was increased, the expression of Beclin-1 was up-regulated, and the expression of p62 was down-regulated at 12 and 36 h after CLP in group Sep and group TMP(P<005). Compared with group Sep, the escape latency was significantly shortened, the rate of time spent in the target quadrant was increased, the LC3Ⅱ∕LC3Ⅰratio was decreased, the expression of Beclin-1 was down-regulated, and the expression of p62 was up-regulated at 12 and 36 h after CLP in group TMP(P<005). Conclusion The mechanism by which tetramethylpyrazine reduces sepsis-associated encephalopa-thy is related to inhibiting autophagy in the hippocampal neurons of rats.
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Objective To evaluate the effect of sevoflurane preconditioning on autophagy in the operated lung tissues of the patients undergoing one-lung ventilation.Methods Forty patients of both sexes,with American Society of Anesthesiologists physical status Ⅰ-Ⅲ,aged 30-80 yr,weighing 45-84 kg,scheduled for elective radical operation for lung cancer performed via video-assisted thoracoscope under general anesthesia,were divided into control group (C group) and sevoflurane preconditioning group (SP group),with 20 patients in each group.In SP group,sevoflurane was inhaled for 30 min with the final concentration of 2.0％,followed by washout.The normal lung tissues (the distance from the edge of the lump＞2 cm) around the lump were obtained for detection of the expression of microtubule-associated protein 1 light chain 3 Ⅱ by Western blot.Results Compared with C group,the expression of microtubule-associated protein 1 light chain 3 Ⅱ in lung tissues was significantly up-regulated in SP group (P＜0.05).Conclusion Sevoflurane preconditioning can enhance autophagy in the operated lung tissues of the patients undergoing one-lung ventilation,which may be related to the lung protective effect.
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Objective To evaluate the effects of different degrees of coagulation disorders after surgery on short-term prognosis in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB).Methods A total of 410 patients of both sexes,aged 18-79 yr,with body mass index of 16-28 kg/m2,of American Society of Anesthesiologists physical status Ⅲ or Ⅳ,scheduled for elective cardiac surgery with CPB,were enrolled in the study.After induction of general anesthesia,the patients were tracheally intubated and mechanically ventilated.Combined intravenous-inhalational anesthesia was used.The patients were divided into 3 groups according to the coagulation function at 6 h after surgery:normal function group (n =55),mild disorder group (n =237) and severe disorder group (n =118).Postoperative mechanical ventilation time,duration of intensive care unit stay,length of hospitalization and complications during hospitalization were recorded.Results Compared with normal function group,the length of hospitalization was significantly prolonged,and the rate of delayed discharge from hospital was increased in mild disorder group,and the ventilation time,duration of intensive care unit stay and length of hospitalization were significantly prolonged,the rate of delayed extubation,rate of prolonged intensive care unit stay and rate of delayed discharge from hospital were increased,and the hepatic and nephritic insufficiency and incidence of re-thoracotomy for bleeding were increased in severe disorder group (P＜0.05),and no significant change was found in the incidence of postoperative complications in mild disorder group (P＞0.05).Conclusion For the patients undergoing cardiac surgery with CPB,postoperative mild coagulation disorders exert no effect on short-term prognosis,however,postoperative severe coagulation disorders produce poor prognosis,and correction of severe coagulation disorders should be taken into account.
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Objective The purpose of this research is to study the preventive and therapeutic effects of suramin on lipopolysaccharide (LPS)-induced mouse model of acute lung injury and its molecular mechanism.Methods A total of 24 healthy male C57BL/6 mice were randomly divided into two groups: Control group and suramin group.LPS (5 mg/kg, iv) induced acute lung injury model was used in this study.The severity of lung injury was evaluated using haematoxylin-eosin (HE) staining after the injection of LPS for 0, 24 and 72 hours.The expression of TNF-α and IL-6 mRNA levels were also detected by RT-PCR.In vitro, THP-1 cells were stimulated by LPS (100 ng/mL) with saline or suramin pre-treatment.The expressions of p-ERK1/2, p-JNK and p-P38 were analyzed by Western blot at 10 min, 20 min and 30 min after LPS insult.A 2-tailed Student's t test was used to compare difference between two independent groups.Results Compared with the saline group, the lung tissues injury were significantly decreased in the suramin group of 72 hours after the injection of LPS (saline 3.90 ±0.35;suramin 2.50 ±0.12) (t =7.668, P ＜ 0.01).The expressions of TNF-α (saline 8.35 ± 1.63;suramin 4.62 ± 0.70) (t =4.187, P＜0.01) andIL-6 (saline10.53 ± 2.10;suramin5.53±1.10) (t=4.224, P＜0.01) mRNA were also obviously reduced in suramin group after the injection of LPS for 24 hours.The expression levels of pERK1/2, p-JNK and p-P38 were obviously down-regulated by suramin at 10 min, 20 min and 30 min after LPS stimulation.Conclusion Suramin protected LPS-induced acute lung injury through down-regulating the expression of pro-inflammatory factors, which was closely relative to the inhibition of the MAPK pathway.
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Objective To evaluate the efficacy of ultrasound-guided sacral block in the obese patients by comparing it with the traditional positioning method.Methods Sixty obese patients,aged 25-50 yr,weighing 56-80 kg,with body mass index ≥ 30 kg/m2,scheduled for elective anorectal surgery,were randomly divided into 2 groups (n =30 each) using a random number table:ultrasound-guided sacral block group (group U) and traditional positioning method group (group T).The sacral canal puncture point was located via either ultrasonic or traditional positioning method.After successful puncture,1％ lidocaine 20 ml was injected.The number of patients in whom puncture was successful at first attempt and the number of patients in whom the time for puncture ≤ 1 min were recorded.The adverse reactions were observed.The efficacy of sacral block was evaluated.Results Compared with group T,the success rate of puncture at first attempt was significantly increased (P ＜ 0.05),and no significant changes were found in the number of patients in whom the time for puncture ≤ 1 min or efffcacy of sacral block in group U (P ＞ 0.05).No adverse reactions were found in the two groups.Conclusion Ultrasound-guided sacral block can raise the success rate of puncture at first attempt and provide similar efficacy of block in the obese patients when compared with the traditional positioning method,and thus has significant clinical value.
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Objective To research the effect of regulating systemic inflammatory response by using ulinastatin in elderly patients after sevoflurane inhalation of postoperation cognitive function. Methods 60 patients under went elective abdominal surgery, were randomly double-blinded divided into 2 groups. Every group had 30 patients.Group A accepted continuously intravenousiy infusion ulinastatin 2000 units · kg-1 · h-1 , while group B got equivalent continuously intravenous infusion 0.9% sodium chloride injection. The time point of opening eye, extubation, response and the mini-mental state examination(MMSE) score on different time points were observed. Meanwhile, the changes of concentration of hs-CRP, IL-6,IL-10 were measured. Results Compared with two groups,group A has shorter time on response(F =4.399,P = 0.040). Two both groups had decrease of MMSE score 1 hour after surgery compared with preoperation(t =7. 732,11. 916, both P ＜ 0.01), and the score were less than the preoperative value of more than 2 points which showed cognitive decline in patients. But group A's rate of decline in MMSE score was lower than group B(F = 7. 582 ,P =0.012). Both groups had the MMSE score decline 6h after surgery (t = 4. 606,8. 615, both P ＜ 0.05). Group A's score was less than the preoperative value for less than 2 points, group B's score was lower than the preoperative value for more than 2 points, but the difference between the two groups was not significant (P ＞0. 05). Both groups had higher concentrations of hs-CRP、IL-6 、IL-10 at postoperative 1 d ,3d ,7d (all P ＜ 0.01), peaked at postoperative 1 d, and hadn't come back to the preoperative level 7d*after surgery. In group A, the concentrations of hs-CRP, IL-6 increased (postoperative 1 d,3d), but the rate was lower than the group B (F = 14. 885, P = 0.000;F = 4. 405, P = 0. 040; F = 18. 204, P = 0.000; F = 8. 074, P = 0. 006); while the increased rate of concentration of IL-10 was higher than the group B(F=5.197,P=0.026;F= 12.236,P =0.000). Conclusion Ulinastatin could promote the elderly after sevoflurane inhalation rapid recovery of cognitive function, which may be related to the regulation of systemic inflammatory response.