1.Role of HO-1 in electroacupuncture-induced alleviation of cognitive dysfunction in mice with sepsis-associated encephalopathy: relationship with mitochondrial fusion-division balance
Rui MU ; Zilei XIE ; Jia SHI ; Lirong GONG ; Jianbo YU
Chinese Journal of Anesthesiology 2021;41(12):1506-1509
Objective:To evaluate the role of heme oxygenase-1 (HO-1) in electroacupuncture (EA)-induced alleviation of cognitive dysfunction in mice with sepsis-associated encephalopathy (SAE) and the relationship with mitochondrial fusion-division balance.Methods:Thirty clean-grade male C57BL/6 mice (24 wide-type mice and 6 HO-1 knockout mice), aged 6-8 weeks, weighing 18-22 g, were studied.Twenty-four wide-type mice were divided into 4 groups ( n=6 each) using a random number table method: control group (group C), SAE group, SAE plus EA group (group SAE+ EA), and SAE plus sham EA group (group SAE+ SEA). HO-1 knockout mice in which EA intervention was performed after establishing SAE model served as SAE plus EA plus HO-1 knockout group (group SAE + EA+ H). Sepsis was induced by intraperitoneally injecting lipopolysaccharide 15 mg/kg.EA of Zusanli and Baihui acupoints lasting 30 min was performed after intraperitoneal injection of lipopolysaccharide once a day for 5 consecutive days in SAE+ EA and SAE+ EA+ H groups.Cognitive function was assessed using Morris water maze test before stimulation every day.The mice were sacrificed, and hippocampal tissues were removed for detection of the expression of mitofusin 2 (Mfn2), optic atrophy 1 (OPA1) and mitochondrial dynamin-related protein 1 (Drp1) by Western blot. Results:Compared with group C, the expression of Mfn2 and OPA1 was significantly down-regulated, the escape latency was prolonged, and the time spent in the target quadrant was shorted in SAE, SAE+ SEA and SAE+ EA+ H groups, and the expression of Drp1 was significantly up-regulated in SAE, SAE+ EA, SAE+ SEA and SAE+ EA+ H groups ( P<0.05). Compared with group SAE, the expression of Mfn2 and OPA1 was significantly up-regulated, the expression of Drp1 was down-regulated, the escape latency was shortened, and the time spent in the target quadrant was prolonged in group SAE+ EA ( P<0.05), and no significant change was found in the parameters mentioned above in group SAE+ SEA ( P>0.05). Compared with group SAE+ EA, the expression of Mfn2 and OPA1 was significantly down-regulated, the expression of Drp1 was up-regulated, the escape latency was prolonged, and the time spent in the target quadrant was shortened in SAE+ SEA and SAE+ EA+ H groups ( P<0.05). Conclusion:HO-1 is involved in EA-induced alleviation of cognitive dysfunction in mice with SAE, and the mechanism may be related to the regulation of mitochondrial mitochondrial fusion-division balance.
2.A retrospective study of electroacupuncture combined with Qingyi decoction as an adjuvant treatment for severe acute pancreatitis-associated lung injury
Dinghuan ZHAO ; Yue DU ; Shihan DU ; Cui LI ; Xinxin HU ; Zilei XIE ; Yuan ZHANG ; Jianbo YU
Chinese Journal of Anesthesiology 2021;41(4):469-473
The clinical data of patients with severe acute pancreatitis admitted to the Department of Intensive Care Unit in our hospital from January 1, 2016 to December 31, 2020 were retrospectively collected.The patients were divided into electroacupuncture combined with Qingyi decoction treatment group (acupuncture group) and conventional group according to whether the patients received electroacupuncture combined with Qingyi decoction treatment.A prediction model of treatment propensity score was established for paired screening, with 122 cases in each group.The acupoints such as Zusanli, Sanyinjiao, Hegu, Shangjuxu, Xiajuxu, and Taichong were selected, and then electroacupuncture treatment was performed after qi arrival using the manipulation technique, 1 or 2 times per day.Qingyi decoction was injected through the stomach and/or Qingyi decoction was given by coloclysis, 2-4 doses per day.The main outcome was the incidence of acute respiratory distress syndrome (ARDS), and the secondary outcome was the occurrence of complications and outcome of discharge.Compared with conventional group, the incidence of ARDS was significantly decreased, the time of mechanical ventilation was shortened, the incidence of renal dysfunction, score for acute physiology and chronic health score system, sequential organ failure score, and score for the severity of bedside acute pancreatitis were decreased, the rate of surgical intervention was increased, the total length of hospital stay was prolonged, and the fatality rate during hospitalization was reduced in acupuncture group ( P<0.05). The results of subgroup analysis showed that the onset time of disease (<1 week), a history of cardiovascular disease, diabetes mellitus, biliary pancreatitis and alcoholic pancreatitis, high fever, puncture and drainage were influencing factors for ARDS developed in the patients who received electroacupuncture combined with Qingyi decoction for treating severe acute pancreatitis.In conclusion, electroacupuncture combined with Qingyi decoction as an adjuvant treatment for severe acute pancreatitis can reduce acute lung injury, promote recovery, and decrease fatality rate.
3.Relationship between SIRT3 and mitochondrial function in mice with endotoxin-induced lung injury
Zilei XIE ; Yue DU ; Jia SHI ; Na LI ; Yuting LI ; Shasha LIU ; Yanfang ZHANG ; Jianbo YU
Chinese Journal of Anesthesiology 2022;42(2):226-230
Objective:To evaluate the relationship between silent information regulator 2 homologue 3 (SIRT3) and mitochondrial function in mice with endotoxin-induced lung injury.Methods:Twenty clean-grade healthy adult male wild C57BL/6 (SIRT3 + /+ ) mice, 20 SIRT3 knockout (SIRT3 -/-) mice, weighing 20-25 g, aged 6-8 weeks, were studied.SIRT3 + /+ mice and SIRT3 -/- mice were divided into 4 groups ( n=5 each) according to the random number table method: blank control group (group C, group SIRT3 -/-C), endotoxin-induced lung injury group (group L, group SIRT3 -/-L), endotoxin-induced lung injury plus resveratrol group (group L+ R, group SIRT3 -/-L+ R), and resveratrol group (group R, group SIRT3 -/-R). Resveratrol 15 mg/kg was intraperitoneally injected once a day for 7 consecutive days in L+ R, R, SIRT3 -/-L+ R and SIRT3 -/-R groups, while the equal volume of normal saline was injected in the rest groups.Lipopolysaccharid 15 mg/kg was injected via the tail vein to develop a mouse model of endotoxin-induced lung injury at 30 min after resveratrol injection on 7th day, in L+ R and SIRT3 -/-L+ R groups and at the corresponding time points in L and SIRT3 -/-L groups, while the equal volume of normal saline was injected in the other groups.Blood samples were collected from the orbital venous plexus at 12 h after injection of normal saline or lipopolysaccharid for determination of serum total oxidation state (TOS) and total antioxidant state (TAS) levels by the xylenol orange method and ABTS colorimetric method, and the oxidative stress index (OSI) was calculated.After the mice were sacrificed, the lung tissues were taken for microscopic examination of the pathological changes which were scored and for determination of the mitochondrial membrane potential (MMP) (by JC-1 method), cellular oxygen consumption rate (OCR) (by the specific fluorescent probe method), and expression of SIRT3 (by Western blot). Results:Compared with group C or group SIRT3 -/-C, the lung injury score, serum TOS concentration and OSI were significantly increased, TAS concentration, MMP and OCR were decreased, and SIRT3 expression was down-regulated in L, L+ R, SIRT3 -/-L and SIRT3 -/-L+ R groups ( P<0.05). Compared with group L, the lung injury score, serum TOS concentration and OSI were significantly decreased, TAS concentration, MMP and OCR were increased, and SIRT3 expression was up-regulated in group L+ R, and lung injury score, serum TOS concentration and OSI were significantly increased, TAS concentration, MMP and OCR were decreased, and SIRT3 expression was down-regulated in group SIRT3 -/-L ( P<0.05). Compared with group L+ R, the lung injury score, serum TOS concentration and OSI were significantly increased, the TAS concentration, MMP and OCR were decreased, and the expression of SIRT3 was down-regulated in group SIRT3 -/- L+ R ( P<0.05). There was no significant difference in the indicators mentioned above between group SIRT3 -/-L+ R and group SIRT3 -/-L ( P>0.05). Conclusions:Down-regulation of SIRT3 expression can lead to impaired mitochondrial function, which is involved in the pathophysiological mechanism of endotoxin-induced lung injury.
4.A retrospective study of cisatracurium besilate-assisted treatment of severe acute pancreatitis complicated with intraabdominal hypertension
Na LI ; Yanfang ZHANG ; Shasha LIU ; Zilei XIE ; Rui MU ; Yuan ZHANG ; Jianbo YU
Chinese Journal of Anesthesiology 2022;42(5):591-594
The clinical data of patients with severe acute pancreatitis complicated with intraabdominal hypertension or abdominal compartment syndrome admitted to our Department of Critical Care Medicine from January 1, 2018 to October 1, 2021 were collected and analyzed.Patients were divided into a conventional treatment group and conventional treatment plus IV infusion of cisatracurium besilate group (muscle relaxation group). A prediction model of treatment propensity score was developed for paired screening, with 31 cases in each group.The conventional treatment group adopted conventional basic treatment methods such as gastrointestinal decompression, spasmolysis and analgesia, fluid therapy, inhibition of gastric acid, suppression of parenzyme, nutritional support, mechanical ventilation, and enemata.In muscle relaxation group, cisatracurium besilate was intravenously infused on the basis of routine treatment with the initial dose of 0.15 mg/kg given to facilitate endotracheal intubation, followed by continuous intravenous infusion at 1-3 μg·kg -1·min -1, and the dose was adjusted according to the patient′s basic vital signs and clinical effects.The primary outcome was survival rate.Secondary outcome measures were changes in intraabdominal pressure, oxygenation index, the number of defecation, volume of defecation, and urination volume before treatment and on 7, 14 and 20 days of treatment.and the recovery time of bowel sounds, length of mechanical ventilation, time of intensive care unit treatment, and total hospitalization costs.Compared with conventional treatment group, the survival rate was significantly increased, the intraabdominal pressure was decreased on 7, 14 and 20 days of therapy, the oxygenation index was increased, the number of defecation and volume of defecation were increased on 7 and 14 days of therapy, urinary volume was increased before treatment and on day 7 of therapy, the recovery time of intestinal sound was significantly shortened ( P<0.05), and no significant change was found in urinary volume on days 14 and 20 of therapy, length of ventilation, time of intensive care unit treatment, and total hospitalization costs in muscle relaxation group ( P>0.05). In conclusion, cisatracurium besilate can improve oxygenation, promote the recovery of intestinal function and improve the survival rate when used to assist the treatment in the patients with severe acute pancreatitis complicated with intraabdominal hypertension.