1.Peroxisome proliferator-activated receptor γ nuclear translocation induced by focal cerebral ischemia-reperfusion in rats
Li SUN ; Yanwei XU ; Hao LIANG ; Guomin SUN ; Yan CHENG
Chinese Journal of Neurology 2010;43(7):512-515
objective To examine nuclear transIocation of peroxisome proliferator-activated receptor γ(PPARγ)in rats following focal cerebral ischemia/reperfusion(I/R),and to explore the significance of altered PPARγ,nuclear translocation in ischemic brain injury.Methods Healthy adult male SD rats underwent 60-min cerebral artery occlusion followed by reperfusion of 4,8,or 24 h,respectively.The cytoplasmic-to-nuclear shuttling of PPARγ was characterized by Western blot,immunohistochemical and immunofluoreseence staining.The effects of PPARγ agonist rosiglitazone (Ros) and antagonist GW9662 on I/R-induced PPARγ nuclear translocation were also examined in the present study. Furthermore,TTC staining war adopted to determine the change in cerebral infarction volume. Results (1)Western blot analysis revealed an increase of PPARγ in the nucleus and a simultaneous reduction in the cytosol following ischemia and reperfusion for 4 h(tcytosol=9.03,tmuclear=27.19,P=0.00).Prolonged the reperfusion further enhanced this I/R induced PPARγ translocation in a time-dependent manner.Using immunohistochemistry and immunofluorescence,nuclear PPAR γ positive staining increased from 48.3%in the sham control to 80.3% following ischemia and reperfusion for 24 h.(2)Western blot analysis revealed that PPARγ agonist Ros further increased I/R-induced nuclear enrichment of PPARγ,whereas PPARγ antagonist GW9662inhibited I/R-stimulated change in PPARγ.(3)When compared to the L/R group using TTC staining,Ros treatment significantly decreased the infarction volume by 48.40%(15.46±4.94 versus 29.96±3.39,t=5.93.P=0.00),whereas GW9662 increased by 58.95%(47.62±4.93 versus 29.96±3.39,t=7.23,P=0.00).Conclusions Cerebral I/R injury induces PPARγ translocation from the cytosol to the nucleus.This change may represent an intrinsic neuroprotective response against brain I/R injury.
3.The inhibitory effect of PNS on brain 3-NT formation in vitro
Chen XIAO ; Li SUN ; Shanshan CAO ; Hao LIANG ; Yan CHENG
Tianjin Medical Journal 2017;45(3):229-233
Objective To study the inhibitory effect of panax notoginseng saponins (PNS) on 3-nitrotyrosine (3-NT) formation in brain induced by heme/NO2 -/H2O2 or ONOO - pathways in vitro. Methods According to the two major pathways of 3-NT formation in vivo, the models of protein nitration induced by heme/NaNO2/H2O2 or ONOO-system were established, respectively, in vitro. Bovine serum albumin (BSA)/rat plasma protein or rat brain homogenate protein were utilized as reactive substrates in both systems. Samples were divided into blank-control group, 3-NT group and PNS group (including low-, medium-and high-concentration subgroups). In 3-NT group, samples were exposed to heme/NaNO2/H2O2 or ONOO-system, respectively, at 37℃for 30 min, whereas in PNS group, samples were pre-incubated with PNS (at final concentrations of 50 mg/L, 100 mg/L, and 200 mg/L) at 37℃for 5 min before the nitrating system exposure. The 3-NT level in each group was detected by Western blot assy. Results Compared with the blank-control group, both heme/NaNO2/H2O2 and ONOO-system can induce significant 3-NT generation in BSA/rat plasma protein or rat brain homogenate protein (P<0.05). Compared with model group, PNS pre-treatment markedly inhibited 3-NT expression in BSA/rat plasma protein in a dose-dependent manner (P<0.05), the inhibitory effect of low intervention on the level of 3-NT in rat brain homogenate protein was not significant (P>0.05). Medium- and high-concentrations of PNS pre-treatment markedly inhibited 3-NT accumulation, with maximum effect at the concentration of 200 mg/L (P<0.05). Conclusion Medium- and high-concentrations of PNS can inhibit 3-NT formation in brain tissue mediated by either heme/NO2-/H2O2 or ONOO-pathways, implying that potential neuroprotective action against 3-NT involves pathological conditions, like trauma, stroke, and neurodegenerative diseases.
4.The protective function of peroxisome proliferator-activated receptor gamma agonist to focal cerebral ischemia-reperfusion injury in mice model
Jinlin SHANG ; Li SUN ; Hao LIANG ; Yan CHENG
Chinese Journal of Neurology 2009;42(3):190-194
Objective To investigate neuroprotective function of peroxisome proliferator-activated receptor gamma (PPARγ) agonist, rosiglitazone against reperfusion injury after focal cerebral ischemia in mice model.Methods To establish cerebral isebemia-reperfusion injury mice model, adult male mice underwent 2 hours of middle cerebral artery occlusion followed by 22 hours reperfusion (MCAO/R). One hour before MCAO/R, mice were treated with either vehicle (MCAO/R group) or rosiglitazone (6 mg/kg, rosiglitazone group). 2,3,5-triphenyhetrazolium chloride (TIC) staining was applied to determine the volume of cerebralinfarction.TheneurologicaldeficitwasscoredatZeaLonga 5-pointscale. Myeloperoxidase (MPO) activity was measured in brain tissue as an index of neutrophil accumulation. RT-PCR, immunohistochemistry and Western blot were performed to examine the mRNA and protein expression of pro-inflammatory mediators (ICAM-1, IL-1β and COX-2).Results (1) The volume of cerebral infarction in rosiglitazone group was significantly decreased from that of MCAO/R group ( 29. 1 ± 6. 6 vs 57.8 ± 9. 7 ,t = 5. 980, P < 0. 01 ), and rosiglitazone markedly improved neurological function in treated mice than MCAO/R mice(1.2 +0.4 vs 3.3 ±0.8, t =5.812, P<0.01). (2) Compared with MCAO/R group, MPO activity in the rosiglitazone-treated group was significantly lower ((0. 049 + 0. 005 ) U/g vs (0. 083 ±0. 008) U/g,t =5. 904, P <0. 01 ). (3) The mRNA and protein expression of pro-inflammatory mediators (ICAM-1, IL-1β and COX-2) in rosiglitazone group were also significantly decreased from those in MCAO/R group, as demonstrated by RT-PCR (0.313 ±0.024, 0.205 ±0.007, 0.359 ±0.060, t = 7.464, 19.656, 29.319, P <0.01, respectively) and Western blot (0.274±0.014, 0.205±0.025, 0. 146±0.015, t=79.909, 21.392, 95. 105, P<0.01, respectively). ConclusionThe present study suggests that PPARγ agonist, rosiglitazone, has neureprotective properties to cerebral ischemia-reperfusian injury and that the protection is partially mediated via anti-inflarmmatory actions.
5.BPD surgery on type 2 diabetes mellitus in GK rats
Liang CHENG ; Xuejun SUN ; Shiyun ZHANG ; Qilong WANG
Journal of Endocrine Surgery 2012;6(6):371-374
Objective To investigate the therapeutic effects and mechanism of biliopancreatic diversion (BPD) surgery on type 2 diabetes mellitus(T2DM) in GK rats.Methods 16 GK rats were randomly divided into 2 groups:BPD surgery group included 10 rats undergoing BPD surgery,sham-BPD group included 6 rats undergoing a sham operation.Fasting plasma glucose,insulin,glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide(GIP)were detected one week before BPD surgery and the 1st week,4th week,10th week,26th week after BPD surgery.Oral glucose tolerance test(OGTT) and insulin tolerance test(ITT) were done in the 10th week after BPD surgery.Results There was no statistical difference in fasting plasma glucose,insulin,plasma GLP-1 or GIP between the 2 groups before surgery.Plasma glucose had significant reduction in BPD group compared to that in the sham group(P <0.05) and insulin level had no significant difference between the 2 groups.Rats in BPD group had significant improvement in glucose tolerance and insulin sensitivity compared to those in the sham group.Serum level of GLP-1 was significantly elevated in BPD group compared to that before surgery (P =0.0337 at the 1st week after surgery; P =0.0002 at the 4th week after surgery,P < 0.0001 at the 10th week after surgery,P <0.0001 at the 26th week after surgery) and that in sham-BPD group(P =0.0354 at the 1st week after surgery,P =0.0032 at the 4th week after surgery,P =0.0001 at the 10th week after surgery,P <0.0001 at the 26th week).Serum level of GIP was significantly lowered in BPD group compared to that before surgery(P =0.0189 at the 1st week after surgery; P =0.0007 at the 4th week after surgery,P =0.0003 at the 10th week after surgery,P <0.0001 at the 26th week after surgery) and that in sham-BPD group(P =0.0089 at the 1st week after surgery,P =0.0002 at the 4th week after surgery,P =0.0006 at the 10th week after surgery,P <0.0001 at the 26th week after surgery).The difference had statistical significance (P <0.05).Conclusion BPD surgery can significantly reduce fasting plasma glucose,improve glucose tolerance and insulin sensitivity.The change of serum levels of GLP-1 and GIP may play the major role in BPD treatment of diabetes mellitus.
6.Clinical significance of BP1 gene expression in human thyroid cancer
Qilong WANG ; Xuejun SUN ; Lingu WANG ; Shiyun ZHANG ; Liang CHENG
Journal of Endocrine Surgery 2013;7(3):218-220
Objective To detect the expression of BP1 gene in thyroid cancer and its relationship with clinicopathological features of thyroid cancer.Methods BP1 gene expression in 60 cases of thyroid cancer tissues and 20 cases of normal thyroid tissues were detected by in situ hybridization and immunohistochemistry.Results The positive expression rate of BP1 mRNA was 78.3 % (47/60) in the 60 cases of thyroid cancer tissues while it was 20% (4/20) in the 20 cases of normal thyroid tissues detected by in situ hybridization.The difference had statistical significance (P < 0.05).Of the 3 pathological types of thyroid cancer,the positive expression rate of papillary carcinoma was 81.6% (40/49),follicular carcinoma 85.7% (6/7),and medullary carcinoma 25.0% (1/4).The expression of BP1 mRNA had statistical difference between medullary carcinoma and other pathological types like papillary carcinoma and follicular carcinoma (P < 0.05).The positive expression rate of BP1 protein was 93.3% (56/60)in the 60 cases of thyroid cancer tissues while it was 10.0% (2/20) in the 20 cases of normal thyroid tissues detected by immunohistochemistry.The difference had statistical significance(P <0.05).Conclusion BP1 gene expression is up-regulated in human thyroid cancer and it is related to tumor stage and pathological type but not related to patients' age,sex or lymph node metastasis.
7.Tongxinluo enhancing proliferation of peripheral blood-derived human endothelial progenitor cells
Xiao-Wei LIANG ; Cheng-Bo SUN ; Hua WANG ; Chun LIANG ; Zong-Gui WU ;
Academic Journal of Second Military Medical University 1985;0(06):-
Objective:To study the effects of Tongxinluo,a traditional Chinese medicine,on the proliferation of peripheral blood-derived endothelial progenitor cells(EPCs)in vitro.Methods:The Tongxinluo solution was prepared through ultrasonication according to the pervious literature.The mononuclear cells(MNCs)were isolated from the peripheral blood with Ficoll by density gradient centrifugation.MNCs were suspended in Medium 199 containing 20% fetal blood serum(FBS)and vascular endothelial growth factor(VEGF).After cultured for 7 d,the attached cells were characterized by Di-LDL uptaking and FITC-lectin binding by laser confocal microscope,and further identified through detection of CD34 and CD133 expression by flow cytometry.Then the cultured EPCs were incubated with Tongxinluo at a series of concentrations(0,50,100,200,500, 750,1000?g/ml)for different durations(0,6,12,24 and 36 h).The cell morphology was observed and cell proliferation was determined by MTT assay.Results:Incubation with different concentrations of Tongxinluo increased the proliferative ability of EPCs.Tongxinluo at 500?g/ml had the most prominent effect on proliferation and the effect increased as time went by and reached peak at 36 h(growth rate 54.18%,P
8.Somatic symptoms and dynamic changes after treatment in elderly inpatients with depression:A 1-year follow-up study
Guichun ZHAO ; Ying LIANG ; Xiao WANG ; Tao LI ; Yao CHENG ; Xinyu SUN
Chinese Mental Health Journal 2015;(3):204-209
Objective:To explore the characteristics of somatic symptoms and their dynamic changes after treatment in elderly inpatients with depression,so as to give supported data in differential diagnosis and management of somatic symptoms in the elderly patients.Methods:Totally 69 consecutively hospitalized depression patients(≥60 years)were enrolled in the study,and 62 of them completed the 12-month follow-up.The diagnoses were made according to International Statistical Classification of Diseases and Related Health Problem-10th revision(ICD-10) criteria.The Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA)and Somatic Symptom Self-rat-ing Scale-Somatic factor(SSS-S)were used to assess the severity of depression,anxiety and somatic symptoms, which were evaluated at baseline,2 weeks,4 weeks and the end of 12-monthr espectively.The Minimum Mental State Examination(MMSE)were used to evaluate cognitive function,and Global Assessment Function(GAF)were used to evaluate social function at the end of 12-month follow-up.Result:Somatic symptoms presented in the all patients at the stages of depressive episode.The most common ones were gastrointestinal symptoms(91%),dizzi-ness or headache(66%),cardiovascular symptoms(59%).SSS-S scores at 2 weeks and 4 weeks of antidepressant treatment were significantly improved compared with those of baseline,[(13.6 ±3.2),(12.4 ±2.8)vs.(17.1 ± 4.8),analyzed by repeated measures of ANOVA,P <0.05].The changes of SSS-S scores were positive associated to the changes of anxiety symptoms and the effect of physical diseases,analyzed by hierarchical linear model analy-sis.At the stages of rehabilitation,residual somatic symptoms were positive associated to the degree of anxiety symptoms(OR =2.132,P <0.05),and unrelated to the level of HAMD,MMSE and GAF scores analyzed by logis-tic regression analysis.Conclusion:Somatic symptoms are various in elderly inpatients with depression during the a-cute phase,which are improved greatly as effective antidepressant treatment,and still have residual somatic symp-toms at the stage of rehabilitation.The effect of physical diseases and anxiety symptoms have influence on somatic symptoms.
9.The Effects of Mild Hypothermia on MODS Caused by Cerebral Hemorrhage
Liang WEI ; Qi WANG ; Cheng YANG ; Yanfei ZHANG ; Hongxin GUAN ; Zhiyang SUN
Journal of Kunming Medical University 2016;37(12):57-61
Objective To disscuss and analyze the clinical effects of whole body mild hypothermia on MODS caused by cerebral hemorrhage.Methods One hundred and eighty patients with MODS caused by cerebral hemorrhage during the period of hospitalized from January 2013 to December 2015 in ICU of our hospital were divided into two groups (observation group and control group) randomly,90 cases patients in each group.Patients in control group were treated with conventional treatment intervention,patients in control group were treated with whole body mild hypothermia on the base of conventional treatment intervention,the score of MODS,the ratio of,VO2 and DO2,the time during the period of hospitalized in ICU,the time of mechanical ventilation,epilepsy incidence and mortality,NIHSS score and PADL score of the patients in these two group after treatment were compared.Results After the comparion,the score of MODS and the state of oxygen consumption and oxygen supply of the patients in observation group were better than the patients in control group,there was significant differences,and had statistical significance (P<0.05);the time during the period of hospitalized in ICU and the time of mechanical ventilation of the patients in observation group were shorter than the patients in control group,there was significant difference,and had statistical significance (P<0.05);the mortality were reduce significantly of the patients in observation group than the patients in control group,there was significant difference,and had statistical significance (P<0.05);the epilepsy incidence of the patients in observation group and control has no significant difference,has no statistical significance (P>0.05);the NIHSS score and PADL score of the patients in observation group were higher than the patients in control group,there was significant difference,and has statistical significance (P<0.05).Conclusion The clinical effects of whole body mild hypothermia on MODS caused by cerebral hemorrhage have important significance,can effectively improve the balance of multiple organ dysfunction syndrome patients,can delay the progression of multiple organ dysfunction syndrome patients,improve the prognosis,it is worthy of clinical application and promotion.
10.Effect of Ticagrelor versus Prasugrel on Platelet Reactivity:A Meta-analysis
Yumeng WU ; Lichun CHENG ; Jing LIANG ; Lilong LIU ; Xiangju SUN ; Jia SONG ; Yubo WU
China Pharmacy 2016;27(15):2083-2086
OBJECTIVE:To systematically review the effect of ticagrelor versus prasugrel on platelet reactivity,and provide evi-dence-based reference for clinical treatment. METHODS:Retrieved from PubMed,CJFD and Wanfang Database,randomized con-trolled trials(RCT)about the effect of ticagrelor versus prasugrel on platelet reactivity were collected. Meta-analysis was performed by using Rev Man software after data extract and quality evaluation by Cochrane 5.1.0. RESULTS:Totally 17 RCTs were enrolled,involv-ing 2 757 patients. Results of Meta-analysis showed,regardless of Verity Now(VN)detection method [MD=15.43,95%CI(-0.39, 31.25),P=0.06] or vasodilator stimulus phosphoprotein(VASP)detection method [MD=-3.04,95%CI(-8.98,2.90),P=0.32], ticagrelor and prasugrel had the same effects on platelet reactivity under loading dose,the differences were not statistically significant;regardless of VN detection method [MD=-48.94,95%CI(-58.04,-39.84),P<0.001] or VASP detection method [MD=-14.32, 95%CI(-20.45,-8.20),P<0.001],the effects of ticagrelor were better than prasugrel on platelet reactivity under maintenance dose,the differences were statistically significant. CONCLUSIONS:At the loading dose,there was no difference between ticagrelor and prasugrel,but ticagrelor has more benefits than prasugrel under maintenance dose.