1.A study on the relevance of eosinophil counts in induced sputum and fractional concentration of exhaled NO and lung functions in asthmatics
Wen WANG ; Kewu HUANG ; Baomei WU ; Yanjun WANG ; Chen WANG
Chinese Journal of General Practitioners 2011;10(11):804-807
Objective To investigate the correlations between eosinophil counts in induced sputum and lung function (FENO) and evaluate these parameters in medication adjustment in patients with asthma.Methods Sixty-five outpatients with mild to moderate persistent asthma ( mild,32 ; moderate,33 ) from January to August 2008 were enrolled in the study.All were treated with combined medications comprising inhaled corticosteroids plus long-acting β2 agonists for 1 year.Lung function (FEV1% and PEF% ),eosinophil counts in induced sputum,FENO,and Asthma Control Test (ACT) scores were obtained at regular follow-up intervals.Twenty-one healthy volunteers served as controls,and lung function,eosinophil counts in induced sputum,and FENO were also obtained.Results Sixty-three subjects completed 1-year or longer follow-up.Lung function of 63 subjects recovered quickly in the early days and improved slowly during the following 6 months.FENO decreased from (61 ± 25 ) nmol/L at baseline to ( 32 ± 19 ) nmol/L by the third month (q =7.32,P<0.05) and to (22 ± 12) nmol/L by the sixth month,which showed significant difference from normal controls [ ( 13 ± 8) nmol/L; q =6.63,P < 0.05 ].Eosinophil counts in induced sputum of the asthma group at baseline were (0.093 ±0.023) × 109/L and decreased to (0.032 ±0.011)× 109/L by the third month,which was significantly different from baseline and normal controls [ (0.005 ±0.003) × 106/ml; q =5.49,P <0.05 and q =5.87,P <0.05,respectively].FENO showed a significantly positive correlation with eosinophil counts in induced sputum in the first 6 months (r1 =0.612,r2 =0.558,r3 =0.675; all P<0.05) and a negative correlation with FEV1 (r1 =-0.537,r3 =-0.658,r6 = -0.623,r9 =-0.537,r12 =-0.597 ; all P <0.05 ) at any time point of the study.The ACT score of 63 subjects at baseline was 14 ±3,and the scores after treatment for 1,3,6,9,and 12 months were 18 ±5,19 ±7,23 ±2,24 ± 1,and 24 ± 1,respectively; at the same time,significant difference was found ( F =5.72,P < 0.05).Effectiveness was found according to the ACT score only 1 month after treatment.Conclusion The parameters of FENO and eosinophil counts in induced sputum were sensitive in the detection of airway inflammation and may be useful in evaluation of the efficacy of treatment and adjustment of medication regimens.
2.Research on immune mechanism of Shengxian decoction in experimental autoimmune myasthenia gravis rats
Junyao XU ; Jie ZHU ; Yang CHENG ; Zhouye WU ; Yidi CHEN ; Baomei XIA ; Haoxin WU
Chinese Journal of Immunology 2016;32(10):1462-1466
Objective:To investigate the immune mechanism of Shengxian decoction in experimental autoimmune myasthenia gravis(EAMG) rats. Methods:Lewis rats were immunized with the rat sequence 97-116 of the AChRαsubunit(Rα97-116) in CFA, 25 of which were successful. They were randomly divided into 5 groups:EAMG model group,prednisone group(5. 4 mg/kg),Shengxian decoction low, medium, high dose groups ( dosage 2. 6 g/kg, 5. 2 g/kg, 10. 4 g/kg ) . Clinical symptoms, weight, and the decrement percentage of RNS(5 Hz) were evaluated,and ELISA were adopted to determine the titers of AChR Ab,TGF-β,IFN-γ,IL-2,IL-4 and IL-17 in serum. Results:After molding,the percentage of decrement of RNS in each group noticeably increased by more than 10% in comparison with that in the CFA control group ( P<0. 01 or P<0. 05 ) . At the same time, they were also subjected to progressive decreasing weight and typical myasthenia symptoms,showing the successful molding. With medication,the decrement percentage of RNS of rats in the groups with low,medium and high dose of Shengxian decoction were all on obvious decline with alleviated weight decrease (P<0. 01),testifying to the symptom improvement. Compared with the CFA control group,the groups with low,medium and high dose of Shengxian decoction were coupled with decreasing AChR Ab content(P<0. 05),rising TGF-βlevel and reducing IFN-γ,IL-2,IL-4 and IL-17 level(P<0. 01 or P<0. 05). Conclusion: Shengxian decoction can turn the decrement percentage of RNS around,improve the progressive weight decrease in EAMG rats and increase the weight gains. By up-regulating the TGF-βlevel,lowering IFN-γ,IL-2,IL-4 and IL-17 level,preventing B cells from producing AChR Ab and reducing the content of AChR Ab in serum,it will soothe the damage of NMJ to AChR and cure EAMG.
3.Influence of Yuejuganmaidazao Decoction on depression-like behavior and m-TOR and Akt expression in hippocampus of PPD offspring
Ruyan WU ; Cai LU ; Weiei TAO ; Baomei XIA ; Wenda XUE ; Li REN ; Haoxin WU ; Gang CHEN
Chinese Pharmacological Bulletin 2016;32(7):1022-1026
Aim To observe the rapid antidepressant effect of Yuejuganmaidazao Decoction on postpatum de-pression offspring , and analyze its influence on the Akt and mTOR expression .Methods After postpartum de-pression model was established , the offsprings were randomly divided into the following groups: control group(CTL-F1,n =8), vehicle group (Veh,n =8) and YG group ( YG, n =8 ) .Veh group was treated with vehicle , YG group was treated with Yueju gan-maidazao Decoction(8.3 g· kg -1 ).Forced swimming test(FST) was measured 24 hours after single adminis-tration.The phosphorylation and total level of Akt and m-TOR in the hippocampus was detected by Western blot.Results The immobility time in YG group was significantly shorter than that in Veh group ( P <0.01 ) , and the expression of p-Akt and p-mTOR in the hippocampus was significantly increased ( P <0.05 ) .Conclusion Yuejuganmaidazao Decoction may rapidly alleviate depression-like behaviors of PPD offsprings through upregulation of Akt and mTOR ex-pression .
4.Effect of yuejuganmaidazaotang in hippocampus in postpartum depression model mice on AKT/mTOR signaling pathway
Baomei XIA ; Chang CHEN ; Hailou ZHANG ; Wenda XUE ; Ruyan WU ; Li REN ; Weiwei TAO ; Gang CHEN
Chinese Pharmacological Bulletin 2016;(1):119-122
Aim Using chronic pre-pregnancy stress to establish a postpartum depression animal model, given a single YG,and acute ketamine was served as control, to explore the pathology of PPD and the anti-depressive mechanism of the YG on the PPD model on AKT/mTOR signaling pathway. Methods Thirty-two fe-male Balb / c were randomly assigned to two groups, the control group ( Control, Con) and the pre-pregnancy stressed group(Model,Mod) , which was subjected to 3 weeks chronic restraint stress. After the last stressor, the pre-pregnancy stressed group was housed with a male. After about 4 weeks later, the mice gave birth to pups. Then at 3 weeks postpartum, we tested the ma-ternal tail suspension test ( TST). Both YG and Ket-amine was single administered 24 hours before behavior test, with single saline for control group and PPD mod-el group. After TST,the mouse hippocampus were ex-tracted to detect the expression of AKT and mTOR. Results After 3 weeks postpartum, the model mice showed depression-like behaviors. Immobility in TST was significantly increased in vehicle groups(P <0. 01). Acute YG improved performance in the TST (P< 0. 01), which was similar to ketamine. And the PPD model mice group showed decreased phosphorylation of AKT and mTOR (P < 0. 01,P < 0. 01), compared to control group. A single dose of YG or ketamine normal-ized AKT/ mTOR signaling in the PPD model mice(P< 0. 01,P < 0. 01),( P < 0. 01,P < 0. 01). Conclu-sions Chronic pre-pregnancy stress can induce dams into postpartum depression and its mechanism maybe associated with down-regulating AKT/ mTOR signa-ling. Acute YG exerts fast antidepressant effect on this PPD model similar to ketamine, and its mechanism may be related to up-regulating AKT/ mTOR signaling in the hippocampus.
5.Postpartum depression animal model in mice and effect of Yuejuganmaidazaotang on PPD model
Baomei XIA ; Hailou ZHANG ; Wenda XUE ; Chang CHEN ; Weiwei TAO ; Haoxin WU ; Gang CHEN
Chinese Pharmacological Bulletin 2015;(9):1324-1327,1328
Aim To establish a postpartum depression animal model,assess the abnormal maternal behaviors of depressive dams,and observe the rapid antidepres-sant effects of the Yuejuganmaidazaotang (YG)on the PPD model.Methods Thirty-two female Balb /c were randomly assigned to two groups,the control group (Control,con)and the pre-pregnancy stressed group (Vehicle,veh),and vehicle was subjected to 3 weeks chronic restraint stress.After the last stressor,the pre-pregnancy stressed group was housed with a male.Af-ter about 4 weeks later,the mice gave birth to pups. Then at 3 weeks postpartum,we tested the maternal depressive-like behaviors,including sucrose preference test,forced swimming test and novelty suppressed feeding test.Both YG and Ketamine were single ad-ministered 24 hours before behavior test,with single saline for control group and PPD model group.Results After 3 weeks postpartum,the vehicle mice showed depression-like behaviors.Reduced preference in drinking sucrose solution was found in SPT (P <0.01 ).Immobility in FST was significantly increased in vehicle groups (P <0.01 ).In NSFT,the vehicle group displayed a significantly increased latency and reduced unit of food intake compared with control group(P <0.01,P <0.01 ).Acute YG improved per-formance in the SPT(P <0.01),FST (P <0.01)and NSF (P <0.01,P <0.01),which was similar to ket-amine.Conclusions Chronic pre-pregnancy stress can induce dams into postpartum depression.Acute YG exert fast antidepressant effect on this PPD model simi-lar to ketamine.
6.Potent rapid antidepressant effects of effective fraction of GJ-PE and up-regulation of BDNF and TrkB
Li REN ; Weiwei TAO ; Yi CHAI ; Shouxue LI ; Xing WANG ; Yuxuan ZHANG ; Li CHEN ; Baomei XIA ; Haoxing WU ; Gang CHEN
Chinese Pharmacological Bulletin 2016;32(9):1224-1230
Aim To identify whether the petroleum e-ther fraction of Gardenia jasminoides Ellis ( GJ-PE ) could effetive exhibit a rapid antidepressant effect and also to investigate the biological mechanism. Methods Tail suspension test ( TST ) , forced swimming test ( FST ) and novelty suppressed-feeding ( NSF ) were used to screen the rapid antidepressant potential of ef-fective fractions of GJ-PE in KM mice at 24 h post a single administration. Tail suspension test ( TST) was also used at 30 min and forced swimming test ( FST ) was used at 2 h to test the initial onset time of effective fractions of GJ-PE in KM mice. Western blot was per-formed to examine the expression of BDNF and p-eEF2 in hippocampus of KM mice at 2 h and 24 h. Results An acute administration of GJ-PE1 decreased the im-mobility time of KM mice in FST at 2 h and 24 h and decreased the latency time in NSF at 24 h. GJ-PE3 de-creased the latency time in NSF at 24 h. GJ-PE4 in-creased the unit food consumption in NSF at 24 h. At 2 h post a single GJ-PE1 treatment, the expression of BDNF was significantly up-regulated while the expres-sion of p-eEF2 was significantly down-regulated. At 24 h post a single GJ-PE1 treatment, the expression of BDNF was significantly down-regulated while p-eEF2 expression was significantly up-regulated. Conclusion GJ-PE1 has the most significant rapid antidepressant potential among the four fractions of GJ-PE. The effec-tive time of GJ-PE1 is 2 h after drug treatment. The mechanism of the rapid antidepressant effect of GJ-PE1 at 2 h is related to the up-regulation of BDNF and down-regulation of p-eEF2 . GJ-PE3 and GJ-PE4 also have some features of rapid antidepressants. GJ-PE2 doesn′t have the rapid antidepressant potential.
7.Nf1 and BDNF Dysregulation in the Prefrontal Cortex Involved in the Pathogenesis of Attention Deficit Hyperactivity
Journal of Medical Research 2017;46(11):54-57
Objective To investigate the interaction between the Nf1 (Neurofibromin 1)and the BDNF (brain derived neurotrophic factor) in the mechanism of attention deficit hyperactivity disorder (ADHD).Methods Spontaneously hypertensive rats were chosen as the experimental group and WKY servesd as control.RT-PCR,Western-blot were used to detect the mRNA and protein expression levels of Nf1 and BDNF.To explore their relationship,BDNF expression levels were detected after Nf1 expression plasmid transferred and transfection in PC12H and CBRH-7919 cells.Results were quantified by Image-pro plus software.Results In the PFC of ADHD model rats SHR,Nf1 expression was abnormally degressive(P =0.000),in common with the expression of BDNF(P =0.000).Ectopic expression of Nf1 further encouraged the expression of BDNF (PC12H:P =0.000,7919:P <0.05).Conclusion Nf1 expression was significantly lower in PFC of SHR than control,and positively correlated with the levels of BDNF.These findings show that in the prefrontal cortex,Nf1-BDNF dysregulation may be involved in the pathomechanism of ADHD.
8.Expression of Disrupted-in-schizophrenia 1 in Hippocampus in Postpartum Depression Animal Models Induced by Pre-pregnancy Stress.
Baomei XIA ; Chang CHEN ; Hailou ZHANG ; Xin ZHOU ; Weiwei TAO ; Haoxin WU ; Gang CHEN
Acta Academiae Medicinae Sinicae 2017;39(2):230-235
Objective To establish a postpartum depression animal model induced by pre-pregnancy stress,assess abnormal maternal depressive-like behavior,observe the expression of disrupted-in-schizophrenia 1 (DISC1) in the hippocampus,and detect serum estradiol and corticosterone.Methods A total of 32 female Balb/c were assigned to two groups using random number table:the control group and the pre-pregnancy stressed group(model group),and the model group was subjected to 3 weeks of chronic restraint stress. After the last stressor,the control group and the model group were housed with a male. About 4 weeks later,the mice gave birth to pups. Then at 3 weeks postpartum,open field test,tail suspension test,and sucrose preference test were carried out. The expressions of DISC1 mRNA and protein of hippocampus were detected by real-time quantitative polymerase chain reaction and Western blot,respectively. The serum levels of estradiol and corticosterone were detected with enzyme linked immunosorbent assay. Results After 3 weeks of postpartum,the model mice showed depression-like behaviors. In the open field test,there was no effect on the total distance moved or time spent in the center field (P>0.05). Immobility in tail suspension test was significantly increased (t=-4.950,P<0.001) and sucrose preference was significantly reduced in model group (t=2.475,P<0.05). There was significant statistical difference between control and model group on the expression of DISC1 mRNA (t=-8.915,P<0.001) and protein (t=-5.004,P<0.01) in hippocampus. There was no significant statistical difference on estradiol and corticosterone between two groups (P>0.05). Conclusion Chronic pre-pregnancy stress can induce dams into postpartum depression.The pathogenesis of postpartum depression may be related to the regulation of DISC1 in the hippocampus.