1.Dexmedetomidine-induced cardioprotection in a mouse model of lung ischemia-reperfusion: the relationship with endoplasmic reticulum stress
Bingqian XIANG ; Ziyin LUO ; Hui GAO ; Yongyue DAI ; Wantie WANG
Chinese Journal of Anesthesiology 2017;37(1):61-65
Objective To evaluate dexmedetomidine-induced cardioprotection in a mouse model of lung ischemia-reperfusion (I/R) and the relationship with endoplasmic reticulum stress.Methods Forty healthy SPF male C57BL/6J mice,weighing 20-24 g,aged 8-10 weeks,were divided into 4 groups (n=10 each) using a random number table:sham operation group (Sham group),lung I/R group (I/R group),dexmedetomidine group (Dex group) and dexmedetomidine plus atipamezole (specific α2-adrenergic receptor antagonist) group (DA group).The model of lung I/R injury was established by clamping the left hilum of lung for 30 min followed by 180 min of reperfusion.In group Sham,only sternotomy was performed,the hilum of lung was not clamped,and the mice were mechanically ventilated for 210 min.In Dex and DA groups,dexmedetomidine 20 μg/kg and dexmedetomidine 20 μg/kg plus atipamezole 250 μg/kg were injected intraperitoneally,respectively,at 30 min before establishment of the model.At 180 min of reperfusion,blood samples were collected from the orbit for determination of creatine kinase-MB (CK-MB) and lactic dehydrogenase (LDH) activities in serum.The animals were then sacrificed,and hearts were removed for determination of apoptosis in cardiomyocytes (by TUNEL) and expression of phosphorylated c-Jun N-terminal kinase (p-JNK),caspase-12,CCAAT/enhancer-binding protein homologous protein (CHOP) and glucose-regulated protein 78 (GRP78) in myocardial tissues (by Western blot),and expression of JNK,caspase-12,CHOP,GRP78 mRNA in myocardial tissues (by real-time polymerase chain reaction).Apoptosis index was calculated.Results Compared with Sham group,the serum CKMB and LDH activities and apoptosis index were significantly increased,the expression of p-JNK,JNK mRNA,and caspase-12,CHOP and GRP78 protein and mRNA was up-regulated in I/R,Dex and DA groups (P<0.01).Compared with I/R group,the serum CK-MB and LDH activities and apoptosis index were significantly decreased,the expression of p-JNK,JNK mRNA,and caspase-12 and CHOP protein and mRNA was down-regulated,the expression of GRP78 protein and mRNA was up-regulated in group Dex,and the expression of GRP78 protein and mRNA was significantly up-regulated (P<0.01),and no significant change was found in the other parameters in group DA (P>0.05).Compared with DEX group,the serum CK-MB and LDH activities and apoptosis index were significantly increased,the expression of pJNK,JNK mRNA,and caspase-12 and CHOP protein and mRNA was up-regulated (P<0.01),and no significant change was found in the expression of GRP78 protein and mRNA in DA group (P>0.05).Conclusion Dexmedetomidine can reduce myocardial injury induced by lung I/R,and the mechanism may be related to activation of α2-adrenergic receptors and inhibition of endoplasmic reticulum stress in myocardial cells of mice.
2.Effects of traditional Chinese medicine Yiqi Huoxue Tongluo Jiedu prescription on pneumocyte apoptosis and c-Jun N-terminal protein kinase pathway in mice after lung ischemia/reperfusion injury
Lu SHI ; Dong SONG ; Xuguang JIA ; Ziyin LUO ; Bingqian XIANG ; Yongyue DAI ; Min LUO ; Wantie WANG
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2017;24(1):73-77
Objective To observe the effects of Yiqi Huoxue Tongluo Jiedu fang (YHTJF) on pneumocyte apoptosis after lung ischemia/reperfusion (I/R) injury (LIRI) in mice and to investigate whether c-Jun N-terminal protein kinase (JNK) is involved in the mechanism of apoptosis.Methods Seventy C57BL/6J male mice were randomly divided into seven groups:normal control group (C group),carboxyl methyl cellulose-Na+normal control group (CMC-Na+C group),CMC-Na+sham group (CMC-Na+S group),CMC-Na+I/R group (CMC-Na+I/R group) and CMC-Na+YHTJF-low,-middle,-high dose groups (CMC-Na+YL,CMC-Na+YM,CMC-Na+YH groups).C group did not undergo any processing;in CMC-Na+S group,only was chest opened without clipping the lung hilum;in the rest of the four groups,they all underwent opening of the chest and clipping the lung hilum for 30 minutes,then the clipping of artery was relieved and left lung reperfusion was carried out for 3 hours.After operation,the mice were sacrificed,the lung tissues were harvested.Under light and electron microscopes,the lung morphological and ultra-structural changes were observed,and the changes of index of quantitative evaluation for alveolar damage (IQA) were determined.The terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) was applied to evaluate the apoptosis index (AI) of the lung tissues.The protein and mRNA expressions of JNK and glucose regulating protein 78 (GRP78) in lung tissues were detected by Western Blot and reverse transcription-polymerase chain reaction (RT-PCR);the correlations between lung AI and the expressions of mRNA and protein of JNK and GRP78,IQA were analyzed.Results Compared with CMC-Na+S group,IQA,AI and mRNA and the protein expressions of JNK and GRP78 in CMC-Na+I/R group were obviously higher [IQA:(74.00 ± 7.31)% vs.(7.00 ± 1.23)%,AI:(64.40 ± 11.97)% vs.(5.60 ± 1.14)%,JNK mRNA (gray value):1.143 ± 0.284 vs.0.152 ± 0.128,GRP78 mRNA (gray value):0.897 ± 0.129 vs.0.284 ± 0.044,JNK protein (A value):0.428 ± 0.074 vs.0.073 ± 0.052,GRP78 protein (A value):1.075 ± 0.145 vs.0.589 ± 0.060].Compared with CMC-Na+I/R group,the IQA,AI,protein and mRNA expressions of JNK and GRP78 in CMC-Na+YL,CMC-Na+YM,CMC-Na+YH groups were all lower,and the degree of reduction in group CMC-Na+YM was the most remarkable,greater than that in CMC-Na+YL or CMC-Na+YH group [IQA:(26.20 ± 3.35)% vs.(34.00±5.34)%,(41.20±9.18)%,AI:(29.40±3.05)% vs.(48.20±3.83)%,(39.20±6.14)%,JNK mRNA (gray value):0.681 ± 0.130 vs.0.804 ± 0.153,0.938 ± 0.11,GRP78 mRNA (gray value):0.450 ± 0.105 vs.0.747 ± 0.231,0.566 ± 0.115,JNK protein (A value):0.188 ± 0.049 vs.0.261 ± 0.065,0.209 ± 0.063,all P < 0.01],compared with the CMC-Na+I/R group,the expression of GRP78 protein was obviously higher in CMC-Na+YH,CMC-Na+YL,CMC-Na+YM groups and the most remarkably high was in CMC-Na+YH group (A value:1.429 ±0.226 vs.1.130±0.169,1.128 ±0.177,all P < 0.01).The apoptosis of each group was mainly in the pulmonary vascular endothelial cells and alveolar epithelial cells,and brown particles were positive cells under light microscope.Under transmission electron microscope:nuclear pyknosis and margination under the nuclear membrane,cytoplasm condensed,lamellar bodies decreased and emptying increased,cell membrane microvilli decreased or disappeared,mitochondria swelling,inflammatory cells increased in alveolar septum and adhering onto the capillary walls could be seen in CMC-Na+I/R group.Compared with CMC-Na+I/R group,the lung tissue ultrastructural damage alleviated,ultrastructure of alveoli clearly seen,nuclear chromatin relatively uniform,cytoplasm increased,type Ⅱ alveolar epithelial cell surface microvilli relatively plenty,lamellar corpuscle number increased,mitochondria swelling ameliorated in CMC-Na+YH,CMC-Na+YL,CMC-Na+YM groups and the most remarkable one was CMC-Na+YM group.AI was significantly positive correlated with the mRNA and protein expressions of JNK,GRP78 and IQA (r =0.907,0.928,0.880,0.712,0.911,all P < 0.01).Conclusions YHTJF may effectively alleviate the cell apoptosis in mice LIRI,and its mechanism may be related to the inhibition of JNK pathway.
3.Sub-health status among migrant workers in Dongguan City and its influencing factors study
Jinlin DU ; Hao LUO ; Yuting GAO ; Zhigang HUANG ; Hairong LIANG ; Jinjie HUANG ; Ziyin LI ; Yuguo LIU
Chongqing Medicine 2018;47(1):79-81
Objective To explore the influencing factors of sub-health status among the migrant workers in Dongguan City.Methods A total of 740 migrant workers in Dongguan city were extracted by the stratified random sampling method.The SubHealth Measurement Scale Version 1.0(SHMS V 1.0) was adopted to test the health status.The data were analyzed by Logistic regression analysis.Results The univariate analysis showed that the marital status,average daily working time,monthly family per capita income,living conditions,drinking,breakfast,nutritional status,vigils,living conditions satisfaction,sedentary desk operation and experiencing negative events had statistical significance(P<0.05).In the Logistic regression analysis:average daily working time,vigils and experiencing negative events were the risk factors of sub-health status occurrence,their odds ratio(OR) and 95 % confidence interval(CI)were 1.971(1.211,3.205),2.183(1.378,3.459) and 2.135(1.353,3.369),respectively.Breakfast and nutritional status were the protective factors of sub-health status occurrence,their OR and 95 % CI were 0.706 (0.526,0.947) and 0.386(0.239,0.625),respectively.Conclusion The unhealthy living habits and experiencing negative events affect the health of migrant workers in Dongguan City.
4.Investigation on the sub-health status of migrant workers in Dongguan City
Yuguo LIU ; Zhigang HUANG ; Hao LUO ; Hairong LIANG ; Huanwen TANG ; Jinjie HUANG ; Ziyin LI ; Jinlin DU
Chongqing Medicine 2017;46(29):4116-4120
Objective To investigate the prevalence and influencing factors of sub-health status of the migrant workers in Dongguan City,in order to provide scientific preferences for preventing sub-health status.Methods Using the stratified random sampling method,740 migrant workers from ten towns(disetricts) in Dongguan city from August 2015 to August 2016 were recruited in this study.The sub-health measurement scale version 1.0 (SHMS V1.0) was applied to evaluate the sub-health status of migrant workers.The SHMS V1.0 scores were compared among migrant workers with different demographic characteristics,and the multivariate linear regression analysis was utilized to explore the influencing factors.Results A total of 718 valid questionnaires were collected,and the effective recovery rate was 97.03%.The sub-health status was detected in 483 migrant workers,and the prevalence rate of sub-health status was 81.6%.The migrant workers' subscale scores of physical sub-health (PS),mental subhealth (MS),social sub-health (SS) and total scale (TS) were (70.25-4-12.25),(64.21± 13.83),(62.21-4-13.87) and (66.114-11.15),respectively.The PS scale scores among migrant workers with different monthly household incomes per capita,and different inhabit situations;the MS scale scores among migrant workers with different ages,educations,marital status,monthly household incomes per capita,and inhabit situations;the SS scale scores among migrant workers with different genders,educations,and inhabit situations;and TS scores mong migrant workers with different educations,monthly household incomes per capita,and inhabit situations were statistically significant different (P<0.05).The multivariate linear regression analysis showed that educations and inhabit situations were the influencing factors for TS score (P<0.05).Conclusion The sub-health status of migrant workers in Dongguan City is serious,and the influencing factors are educations and inhabit situations.
5.Effects of dexmedetomidine on JNK in A549 cells with hypoxia/reoxygenation injury
Ziyin LUO ; Bingqian XIANG ; Hui GAO ; Xiaoxiao QIU ; Xiaoying QIAN ; Wantie WANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2017;22(12):1346-1351
AIM:To investigate the effects and c-Jun N-terminal kinase(JNK) expression of dexmedetomidine (DEX) on A549 cells with hypoxia/reoxygenation (H/R) injury.METHODS:A549 cells were cultivated and were randomly divided into four groups (n =10):control group (N),DEX group (D),hypoxia/reoxygenation injury group (H),hypoxia/reoxygenation injury + DEX interfere group (HD).After all models were completed,the morphological changes of A549 cells were observed under the inverted microscope.Cell activity was detected by CCK-8 and the apoptosis index (AI) was detected by in situ end labeling (TUNEL) method.The expression of GRP78,p-JNK,caspase-3 at protein levels and GRP78,JNK mRNA were detected by Western blot and RT-PCR.RESULTS:Compared with N group,the number of adherent cells in H group decreased significantly,and cell morphology changed.The expression of OD value in H group decreased obviously (P < 0.01),the expression of AI value,GRP78,p-JNK,caspase-3 protein and GRP78,JNK mRNA were significantly increased (P< 0.01).HD group compared with H group,the cell damage alleviated,the expression of OD value was increased (P < 0.01),the number of apoptosis cells and the AI value in HD group were significantly decreased (P < 0.01).Dramatically decreased the expression of p-JNK,caspase-3 protein and JNK mRNA (P < 0.01).CONCLUSION:DEX can effectively alleviate A549 cells damage induced by H/R injury,which may be related to inhibition of the JNK pathway.