2.Role of p38MAPK signal transduction pathway in dexmedetomidine against neurotoxicity induced by bupivacaine
Bin ZHOU ; Fan XIAO ; Dan HUANG ; Fuzhou HUA ; Jun LU ; Guohai XU ; Zhenzhong LUO
The Journal of Clinical Anesthesiology 2017;33(3):281-285
Objective To evaluate the role of p38 MAPK signal transduction pathway in dexmedetomidine against neurotoxicity induced by bupivacaine.Methods Seventy-two adult male SD rats,successfully implanted with intrathecal catheter without complications,were randomly divided into 6 groups: control group (group C);p38MAPK inhibitor group(group SB);dexmedetomidine group (group D);bupivacaine group (group B);dexmedetomidine and bupivacaine group (group DB);p38MAPK inhibitor and bupivacaine group (group SBB).DMSO 20 μl were injected intrathecally in group C;p38MAPK inhibitor 30 μg and 5% bupivacaine were respectively injected intrathecally in group SB and B;group DB and SBB were respectivel pretreated with dexmedetomidine 75 μg/kg intraperitoneally and p38MAPK inhibitor 30 μg intrathecal injection 20 min before intrathecally injected 5% bupivacaine.Dexmedetomidine 75 μg/kg was injected intraperitoneally in group D.Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured before intrathecal catheter was implanted (T0),before intrathecal administration (T1) and at 4,8 and 12 h and on 1,2,3,4,5 and 6 days after intrathecal administration (T2-T10).At 24 h after intrathecal administration,6 rats were randomly chosen from each group and sacrificed.The lumbar segment (L4-5) of the spinal cord was removed for detecting neuronal apoptosis (by TUNEL) and phosporylated p38MAPK(p-p38MAPK) expression (by Western blot).Results Compared with T0,MWT was significantly increased and TWL was prolonged at T2-T9 in group B,MWT at T2-T7 was significantly increased and TWL at T2-T6 was prolonged in group DB,MWT was significantly increased and TWL was prolonged at T2-T5 in group SBB (P<0.05).Compared with group C,no significant difference was found in MWT,TWL,the apoptotic index and expression of p-p38MAPK in groups D and SB.MWT was significantly increased and TWL was prolonged at T2-T9 in group B,the apoptotic index and expression of p-p38MAPK were significantly increased in group B (P<0.05).Compared with group B,MWT and TWL at T2-T9,the apoptotic index and expression of p-p38MAPK were significantly decreased in groups DB and SBB (P<0.05).Conclusion Dexmedetomidine can inhibit spinal neurotoxicity induced by bupivacaine in rats via inhibiting apoptosis in spinal cord,and inhibition of p38 MAPK signal transduction pathway may be involved in the underlying mechanism.
3.Role of JNK signaling pathway in dexmedetomidine-induced reduction of spinal neurotoxicity induced by lidocaine in rats
Bin ZHOU ; Fan XIAO ; Dan HUANG ; Fuzhou HUA ; Guohai XU ; Zhenzhong LUO
Chinese Journal of Anesthesiology 2015;35(10):1207-1210
Objective To evaluate the role of C-Jun N-Terminal kinase (JNK) signaling pathway in dexmedetomidine-induced reduction of spinal neurotoxicity induced by lidocaine in rats.Methods Seventy-two adult male Sprague-Dawley rats, weighing 280-320 g, in which intrathecal catheters were successfully implanted without complications, were randomly divided into 6 groups (n =12 each) using a random number table: control group (group C);SP600125 (JNK signaling pathway blocker) group (group SP);dexmedetomidine group (group D);lidocaine group (group L);dexmedetomidine + lidocaine group (group DL);SP600125+lidocaine group (group SPL).Dimethyl sulfoxide (DMSO) 20 μl was injected intrathecally in group C.SP600125 30 μg and 10% lidocaine 20 μl were injected intrathecally in SP and L groups, respectively.At 20 min after intrathecal injection of 10% lidocaine, dexmedetomidine 75 μg/kg was injected intraperitoneally in group DL, and SP600125 30 μg was injected intrathecally in group SPL.Dexmedetomidine 75 μg/kg was injected intraperitoneally in group D.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured before intrathecal catheters were implanted (T0), before intrathecal administration (T1), and at 4, 8 and 12 h and 1, 2, 3, 4, 5 and 6 days after intrathecal administration (T2-10).At 24 h after intrathecal administration, 6 rats randomly selected from each group were sacrificed.The lumbar segment (L4-5) of the spinal cord was removed for detection of cell apoptosis (by TUNEL) and phosphorylated JNK (p-JNK) expression (by Western blot).The apoptotic index was calculated.Results Compared with group C, no significant change was found in the MWT, TWL, apoptotic index and expression of p-JNK in SP and D groups (P>0.05), the MWT at T2-8 in group L, at T2-6 in group DL and at T2-5 in group SPL were significantly increased, the TWL at T2-8 in group L, at T2-5 in group DL and at T2-4 in group SPL were prolonged, and the apoptotic index and expression of p-JNK were increased in DL, SPL and L groups (P<0.05).Compared with group L, the MWT was significantly decreased, and the TWL was shortened at T2-8, and the apoptotic index and expression of p-JNK were decreased in DL and SPL groups (P<0.05).Conclusion The mechanism by which dexmedetomidine mitigates spinal neurotoxicity induced by lidocaine is related to inhibited activation of JNK signaling pathway in rats.
4.Determination of the Initial Time of Peripheral Pulmonary Lesion by Real-time Contrast-enhanced Ultrasound
Dan LIU ; Aiyun ZHOU ; Cheng ZHANG ; Fan XIAO ; Wan ZHU ; Liyun LUO
Chinese Journal of Medical Imaging 2017;25(4):274-277
Purpose To evaluate the value of real-time contrast-enhanced ultrasound (CEUS) combined with comparative observation in determining the initial time of peripheral lung lesion,and to provide a new method for the diagnosis of peripheral lung disease by CEUS.Materials and Methods Sixty patients with peripheral lung disease diagnosed by chest X-ray or CT examination were examined by CEUS,and the lesions and perfusion of surrounding lung tissue were observed in real time and comparatively.The time of initial enhancement of peripheral lung lesion was determined by real-time comparative observation method,that is,to compare the time of contrast agent to reach the peripheral lung lesion with the time to reach the adjacent gas-containing lung tissue.All lesion specimens were obtained by surgery or ultrasound-guided percutaneous biopsy,and the pathological diagnosis was performed.According to the pathological results,the peripheral lung lesions were classified into the malignant group,the chronic inflammation group and the pneumonia group.Results Sixty cases of peripheral lung lesions were identified as 38 cases of malignant tumors (including 15 cases ofsquamous cell carcinomas,9 cases of adenocarcinoma cell carcinomas,2 cases of large cell carcinomas,9 cases of small cell carcinomas and 3 cases of metastatic carcinomas),14 cases of chronic inflammation lesions (including 7 cases of tuberculomas,3 cases of inflammatory pseudotumors and 4 cases of lung abscess) and 8 cases of pneumonia.The detection rates of pulmonary arterial phase and bronchial artery phase using the real-time comparative observation method were 100% (60/60) and 85% (51/60),respectively.The initial time of pulmonary arterial phase and bronchial artery phase were (6.1 ± 0.9) s and (10.5 ± 1.6) s,respectively.The initial time of pulmonary arterial phase was sooner than bronchial artery phase,the difference was statistical significance (P<0.05).Conclusion The real-time CEUS combined with comparative observation method has important diagnostic value in judging the initial enhancement time of peripheral lung lesion and can provide a new method for the accurate diagnosis of peripheral lung disease,which is worth popularizing.
5.Effects of sevoflurane post-conditioning on oxidative stress and inflammatory reaction during rat cerebral ischemia-reperfusion
Dan ZHAO ; Linhui YUAN ; Jing ZHANG ; Ping ZHANG ; Peng YU ; Fan XIAO ; Xiaoling HU ; Yanhui HU
The Journal of Clinical Anesthesiology 2017;33(7):688-692
Objective To investigate the effects of sevoflurane post-conditioning on oxidative stress and inflammatory reaction during rat cerebral ischemia-reperfusion, and to explore its cerebral protective mechanism.Methods Thirty-six health male Sprague-Dawley rats (aged 12-14 weeks, weighing 220-260 g) were randomly divided into 3 groups (n=12 each): sham control group (group Sham), cerebral ischemia-reperfusion group (group IR), sevoflurane post-conditioning group (group SPC).Cerebral ischemia-reperfusion model was established, ischemia for 30 min followed by reperfusion 24 h.Rat middle cerebral artery was not occluded in group Sham.Cerebral ischemia-reperfusion model was established in group IR.Group SPC was subjected to 2.6% sevoflurane for 15 min in the beginning of reperfusion.At the end of reperfusion, rats were cut off the head to take out the brain tissue.The expression level of Iba-1 and HO-1 proteins was measured by western blot.The levels of reactive oxygen species (ROS), malondialdehyde (MDA), TNF-α, IL-1β and the activity of superoxide dismutase (SOD) were evaluated.Results Compared with group Sham, the expression of cerebral cortex Iba-1 protein was higher than that in groups IR and SPC (P<0.05), the expression of Iba-1 protein in group SPC was lower than that in group IR (P<0.05).Compared with group Sham, the contents of ROS, MDA, TNF-α and IL-1β were increased in groups IR and SPC (P<0.05), but the activity of SOD and expression of HO-1 protein were decreased (P<0.05).And the contents of ROS, MDA, TNF-α and IL-1β in group SPC were less than those in group IR, the activity of SOD and expression of HO-1 protein in group SPC were higher than those in group IR.Conclusion Sevoflurane post-conditioning can mitigate the microglia activation, reduce cerebral oxidative stress and inflammation, thus protect rat cerebral against ischemia reperfusion injury.
6.Effects of rapamycin preconditioning on lung injury induced by limb ischemia-reperfusion in rats
Dan HUANG ; Fan XIAO ; Xiaolan ZHENG ; Zhenzhong LUO ; Guohai XU ; Bin TANG
The Journal of Clinical Anesthesiology 2017;33(7):693-696
Objective To discuss the effects and related mechanisms of rapamycin preconditioning on lung injury induced by limb ischemia-reperfusion (IR) in rats.Methods Sixty healthy male SD rats, aged 4-5 months, weighing 250-300 g, were randomly divided into 5 groups (n=12 each) using a random number table: sham operation group (group S);limb ischemia-reperfusion group (group IR);rapamycin 1, 5, 10 mg/kg pretreatment groups (groups R1, R5 and R10).Ischemia-reperfusion of limb was produced by occlusion of bilateral femoral arteries for 2 h followed by 3 h reperfusion.Blood samples were collected to determine serum superoxide dismutase (SOD), malondialdehyde (MDA), interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) concentrations,1ungs were removed for microscopic examination and for determination of wet/dry lung weight ratio.Results The activity of SOD in groups IR, R1 and R5 was significantly lower than that in group S (P<0.05).The activity of SOD in groups R1, R5 and R10 was significantly higher than that in group IR, that in groups R5 and R10 was significantly higher than that in group R1, that in group R10 was significantly higher than that in the group R5 (P<0.05).Serum MDA, IL-1β, IL-6, TNF-α concentrations and wet/dry lung weight ratio were significantly increased in groups IR, R1 and R5 (P<0.05).Serum MDA, IL-1β, IL-6,TNF-α concentrations and wet/dry lung weight ratio were lower in groups R1, R5 and R10, those in groups R5 and R10 were significantly lower than those in group R1, those in group R10 was significantly lower than those in group R5 (P<0.05).Compared with group S, the lung tissue injured more significantly in group IR.Compared with group IR, the lung tissue injury gradually reduced in groups R1,R5 and R10.Conclusion Rapamycin pretreatment can reduce lung injury caused by limb ischemia-reperfusion injury in rats in a dose-dependent manner, the greater the dose, the stronger the effect of reducing lung injury caused by limb ischemia-reperfusion injury.The mechanisms may involve attenuating oxidative stress and inhibiting inflammatory response.
7.Blood-retinal barrier as a converging pivot in understanding the initiation and development of retinal diseases.
Xue YANG ; Xiao-Wei YU ; Dan-Dan ZHANG ; Zhi-Gang FAN
Chinese Medical Journal 2020;133(21):2586-2594
Clinical ophthalmologists consider each retinal disease as a completely unique entity. However, various retinal diseases, such as uveitis, age-related macular degeneration, diabetic retinopathy, and primary open-angle glaucoma, share a number of common pathogenetic pathways. Whether a retinal disease initiates from direct injury to the blood-retinal barrier (BRB) or a defect/injury to retinal neurons or glia that impairs the BRB secondarily, the BRB is a pivotal point in determining the prognosis as self-limiting and recovering, or developing and progressing to a clinical phenotype. The present review summarizes our current knowledge on the physiology and cellular and molecular pathology of the BRB, which underlies its pivotal role in the initiation and development of common retinal diseases.
Blood-Retinal Barrier
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Diabetic Retinopathy
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Humans
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Macular Degeneration
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Phenotype
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Retinal Diseases
8.Multiple analysis on the gastric impetus associated factors in patients with liver cirrhosis.
Xiao-dan TANG ; Hong FAN ; Ping WAN ; Yun WANG
Chinese Journal of Hepatology 2004;12(3):141-143
OBJECTIVETo investigate mechanism and relation of some disorder motive forces of digest system in patients with liver cirrhosis.
METHODSPlasma vasoactive intestinal peptide (VIP), gastrin and motilin (MTL), electrogastrogram (EGG) and pH value of gastric juice in 24 hours; gastric elimination time by isotope. All above factors have been determined in patients with liver cirrhosis and analyzed with multiple linear regressions. While a group of normal cases has been observed as control.
RESULTSCompared to the control group, higher level of VIP and Gastrin and lower MTL down were observed in liver cirrhosis group (Plasma VIP, Gastrin and MTL are 14.8+/-4.8, 58.6+/-29.8 and 360+/-54.2 separately, t=5.181, 0.05, t=3.871, 0.01 and t=5.529, 0.05 separately). The EGG dominant frequency (DF) and dominant power (DP) decreased around diet; normal slow wave number (N%) decreased and gastric excretion time prolonged, lower bradygastrias (B%) and pH value of 24 hours gastric juice denoted the incline of return movement, there are remarked different with 0.05 or 0.01 separately. Throughout analyzing these factors with multiple linear regressions, there are remarkable relationship between liver cirrhosis and pH value of gastric juice; gastrointestinal hormone and EGG with 0.05 or 0.01.
CONCLUSION(1) There are remarkable gastro esophageal function abnormal which has been conveyed by disorder gastric electric physiology and gastric elimination time in patients with liver cirrhosis. It is suggested that unusual gastrointestinal hormone played an important role during these abnormal process. (2) There is remarkable changing of pH value of 24 hours gastric juice denoted the opposite movement of gastroduodenal juice in patients with liver cirrhosis.
Female ; Gastric Acidity Determination ; Gastric Emptying ; Gastrointestinal Motility ; Humans ; Liver Cirrhosis ; physiopathology ; Male ; Middle Aged ; Vasoactive Intestinal Peptide ; blood
9.Influence of fluoride on osteoprotegerin mRNA and protein expression in rat osteoblasts: an in vitro study
Dan, LI ; Xing-quan, JIANG ; Xiao-feng, JI ; Zhi-tao, ZHAO ; Zhe, FAN ; Ling, JING ; Guang-sheng, LI
Chinese Journal of Endemiology 2009;28(2):134-137
Objective To study the influence of fluoride on the expression of osteoprotegerin(OPG) mRNA and protein in suckling rat osteoblasts. Methods Osteoblasts obtained from calvarial of suckling Wistar rats were cultured in vitro in the media supplemented with NaF at a series of doses[O(control), 1,2 and 4 mg/L groups], and OPG mRNA expression and protein were evaluated by RT-PCR and ELISA methods, respectively. Results OPG mRNA expression in suckling rat osteoblasts cultured in vitro significantly increased after exposure to NaF for 48 h and 72 h(F=333.48,808.34,P<0.05). OPG mRNA expression in suckling rat osteoblasts cultured in vitro after exposure to NaF for 48 h at different doses(0.810±0.003, 0.819±0.031 and 0.870±0.044 for 1,2 and 4 mg/L groups, respectively) compared with that of control (0.800±0.040, all P<0.05). OPG mRNA expression further increased for 72 h exposure to NaF(0.933±0.047,1.031±0.051,1.240±0.062 for 1,2 and 4 mg/L, respectively), significantly higher than that of the control (0.805±0.020,all P<0.05) and corresponding groups at 48 h. NaF doses and time exposure exhibited a significant synergistic effect on OPG mRNA expression(F=2004.16, P<0.05). NaF also enhanced OPG protein expression in suckling rat osteoblasts cultured in vitro. Significant differences were observed only in 4 mg/L group(0.228±0.014,0.277±0.048) and control(0.205±0.012,0.229±0.010) at 48 h and 72 h (P<0.05). In addition, OPG protein expression at 72 h post-exposure was higher than that at 48 h,but there was no synergistic effect between concentration and time(F=1.21,P>0.05). Conclusions The results suggested that NaF could increase OPG mRNA and protein expression in suckling rat osteoblasts with a synergistic effect between the doses and exposure time.
10.Effects of fluid resuscitation on thoracoabdominal injury combined with hemorrhagic traumatic shock
Zhi-Wei FAN ; Xiao-Guang LU ; Xin KANG ; Wei-Guang LIU ; Yi-Gang WANG ; Dan WANG ; Hong-Gang PANG ;
Chinese Journal of Emergency Medicine 2006;0(11):-
Objective To study effects of fluid resuscitation on thoracoabdominal injury combined with hemorrhagic traumatic shock.Method A total of 98 patients,who were treated in Affiliated Zhongshan Hospital of Dalian University from November 2004 to December 2006,were retrospectively analyzed.The patients were diagnozed according to Surgery(fifth edition).Patients were divided into delayed fluid resuscitation group(n= 51)and immediate fluid resuscitation group(n=47).Patients in delayed fluid resuscitation group were given with balanced salt solution for the body to maintain basic requirements.Patients in immediate fluid resuscitation group were rapidly administered with a lot of isotonic crystaUoid and(or)colloid solution after admission. Hemoglobin,platelet count,hematocrit,blood lactic acid,basedeficit,preoperative resuscitation time and mortality were compared between the two groups.Paired t test and variance analysis or x~2 test were used.Results The transfusion fluid volume of delayed group and immediate group was(1586?346)ml,(3520?575)ml, respectively,with P value