Objective To observe the effect of self-formulated Tongluo Yizhi formula on memory deficits and endoplasmic reticulum stress (ERS) in rats with vascular dementia (VD) and its mechanism. Methods Fifty SPF-grade Wistar rats were randomly divided into sham surgery group,model group,TLYZF low-dose (12.5 mg/kg/d) group,TLYZF medium dose (25 mg/kg/d) group and TLYZF high-dose (50 mg/kg/d) group,with 10 rats in each group. Except for the Sham group,other rats were subjected to modified bilateral carotid artery ligation to construct VD models. After 4 weeks of TLYZF intervention,Morris water maze experiment was used to evaluate the learning and memory abilities of rats.Hematoxylin eosin staining was used to detect the pathological structure of the hippocampus.Nissl staining was used to detect hippocampal neuronal damage.In situ end transfer enzyme labeling staining was used to detect hippocampal neuronal apoptosis.Enzyme-linked immunosorbent assay was used to detect the content of inflammatory factors in hippocampal tissue.Protein immunoblotting was used to detect apoptosis of hippocampal tissue cells and the expression of ERS related proteins.Results Compared with the Sham group,the average escape latency of the model group was prolonged(t=14.059),the number of crossing the platform was reduced(t=8.534),the hippocampal neurons were disorderly arranged,the morphology was fuzzy,the cytoplasmic vacuolization,the nuclear pyknosis,the inflammatory cell infiltration increased,the number of Nissl bodies decreased(t=17.131),and the neuronal apoptosis rate increased(t=17.701). The contents of tumor necrosis factor-α (TNF-α),interleukin-1 β (IL-1β) and IL-6 increased(t=6.541,6.957,10.014),the expression of Bcl-2 associated X protein (Bax),cleaved caspase-3,glucose-regulated protein 78 (GRP78),phosphorylated endoplasmic reticulum kinase (p-PERK)/PERK,phosphorylated eukaryotic initiation factor 2α (p-eIF2α)/eIF2α,activating transcription factor 4 (ATF4) and CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP) increased(t=13.548～76.468),while the expression of B-cell lymphoma-2 (Bcl-2) proteinwas decreased (t=39.691),and the difference were statistically significant (all P<0.05),respectively. Compared with the model group,the average escape latency of TLYZF-treated rats was shortened(t=2.476,7.266,11.306),the number of platform crossing was increased(t=2.187,4.471,6.932),the hippocampal neurons were relatively regular,the nucleus was clear,the inflammatory cell infiltration was significantly reduced,the content of Nissl bodies was increased(t=4.359,9.477,11.449),the apoptosis rate of neurons was decreased(t=3.631,6.145,7.580),the contents of TNF-α,IL-1β and IL-6 were decreased (t=2.382～8.293),the expression of Bax(t=4.696,16.250,20.250),cleaved caspase-3(t=15.205,27.000,26.833),GRP78(t=5.918,13.139,13.741),p-PERK/PERK(t=13.416,14.230,17.889),p-eIF2α/eIF2α(t=20.152,39.346,50.750),ATF4(t=12.093,24.395,22.946)and CHOP protein((t=21.592,19.207,22.136)decreased,while Bcl-2 protein increased(t=7.474,20.761,35.350),the differences were statistically significant (all P<0.05),respectively,and the high-dose group had the best therapeutic effect.Conclusion Self-formulated Tongluo Yizhi formula could reduce the apoptosis and inflammatory injury of hippocampal neurons in VD rats,and its mechanism may be related to inhibiting ERS mediated by PERK.

Objective To observe the effect of self-formulated Tongluo Yizhi formula on memory deficits and endoplasmic reticulum stress (ERS) in rats with vascular dementia (VD) and its mechanism. Methods Fifty SPF-grade Wistar rats were randomly divided into sham surgery group,model group,TLYZF low-dose (12.5 mg/kg/d) group,TLYZF medium dose (25 mg/kg/d) group and TLYZF high-dose (50 mg/kg/d) group,with 10 rats in each group. Except for the Sham group,other rats were subjected to modified bilateral carotid artery ligation to construct VD models. After 4 weeks of TLYZF intervention,Morris water maze experiment was used to evaluate the learning and memory abilities of rats.Hematoxylin eosin staining was used to detect the pathological structure of the hippocampus.Nissl staining was used to detect hippocampal neuronal damage.In situ end transfer enzyme labeling staining was used to detect hippocampal neuronal apoptosis.Enzyme-linked immunosorbent assay was used to detect the content of inflammatory factors in hippocampal tissue.Protein immunoblotting was used to detect apoptosis of hippocampal tissue cells and the expression of ERS related proteins.Results Compared with the Sham group,the average escape latency of the model group was prolonged(t=14.059),the number of crossing the platform was reduced(t=8.534),the hippocampal neurons were disorderly arranged,the morphology was fuzzy,the cytoplasmic vacuolization,the nuclear pyknosis,the inflammatory cell infiltration increased,the number of Nissl bodies decreased(t=17.131),and the neuronal apoptosis rate increased(t=17.701). The contents of tumor necrosis factor-α (TNF-α),interleukin-1 β (IL-1β) and IL-6 increased(t=6.541,6.957,10.014),the expression of Bcl-2 associated X protein (Bax),cleaved caspase-3,glucose-regulated protein 78 (GRP78),phosphorylated endoplasmic reticulum kinase (p-PERK)/PERK,phosphorylated eukaryotic initiation factor 2α (p-eIF2α)/eIF2α,activating transcription factor 4 (ATF4) and CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP) increased(t=13.548～76.468),while the expression of B-cell lymphoma-2 (Bcl-2) proteinwas decreased (t=39.691),and the difference were statistically significant (all P<0.05),respectively. Compared with the model group,the average escape latency of TLYZF-treated rats was shortened(t=2.476,7.266,11.306),the number of platform crossing was increased(t=2.187,4.471,6.932),the hippocampal neurons were relatively regular,the nucleus was clear,the inflammatory cell infiltration was significantly reduced,the content of Nissl bodies was increased(t=4.359,9.477,11.449),the apoptosis rate of neurons was decreased(t=3.631,6.145,7.580),the contents of TNF-α,IL-1β and IL-6 were decreased (t=2.382～8.293),the expression of Bax(t=4.696,16.250,20.250),cleaved caspase-3(t=15.205,27.000,26.833),GRP78(t=5.918,13.139,13.741),p-PERK/PERK(t=13.416,14.230,17.889),p-eIF2α/eIF2α(t=20.152,39.346,50.750),ATF4(t=12.093,24.395,22.946)and CHOP protein((t=21.592,19.207,22.136)decreased,while Bcl-2 protein increased(t=7.474,20.761,35.350),the differences were statistically significant (all P<0.05),respectively,and the high-dose group had the best therapeutic effect.Conclusion Self-formulated Tongluo Yizhi formula could reduce the apoptosis and inflammatory injury of hippocampal neurons in VD rats,and its mechanism may be related to inhibiting ERS mediated by PERK.

Objective:To observe any effect of moderate-intensity exercise on left ventricular remodeling (such as cardiomyocyte hypertrophy, apoptosis and proliferation) in spontaneously-hypertensive rats (SHRs) and explore the possible mechanisms.Methods:Thirty 4-month-old female SHRs were randomly divided into a sedentary group ( n=15) and an exercise group ( n=15). Fifteen Wistar Kyoto rats served as the control group. The exercise group underwent daily 60-min moderate-intensity treadmill exercise 5 days per week for 12 weeks, while the sedentary and control groups were raised quietly in cages for the same period. After the 12-week intervention, the caudal artery blood pressure was measured using a non-invasive blood pressure monitor. The rats were then sacrificed and their hearts were sampled for morphometric measurement. Cardiomyocytes were isolated and underwent DAPI staining to measure their length, width and area. Apoptosis cardiomyocytes was detected by using terminal-deoxynucleoitidyl transferase mediated nick end labeling and their proliferation was assessed using immunofluorescent staining. The number of cardiac progenitor cells was detected by flow cytometry, while the expression of the cardiac calcineurin Aβ subunit (CNAβ) and phosphorylated Akt (p-Akt) protein were measured using western blotting. Results:Compared with the control group, a significant increase was observed in the heart weight, heart mass index (HMI), systolic blood pressure, diastolic blood pressure, myocardial thickness of the left ventricular wall (anterior wall, posterior wall and septal wall), cardiomyocyte morphology (length, width and area), cardiomyocyte apoptosis rate, proliferation rate, number of cardiac progenitor cells and protein expression of CNAβ in the sedentary group. Compared with the sedentary group, the average heart weight, HMI, myocardial thickness of the left ventricular wall (anterior wall, posterior wall and septal wall), cardiomyocyte morphology (length, width and area), cardiomyocyte proliferation rate, number of cardiac progenitor cells and p-Akt protein expression had increased significantly in the exercise group. The average systolic blood pressure, diastolic blood pressure, apoptosis rate and CNAβ protein expression had decreased significantly.Conclusions:Moderate-intensity exercise can induce physiological cardiac hypertrophy in SHRs, relieve apoptosis, increase the number of cardiac progenitor cells and promote cell proliferation, thereby inhibiting cardiac remodeling.

Objective To analyze the correlation between the fractional exhaled nitric oxide (FeNO) levels and blood eosinophil (EOS) count and the frequency of wheeze in infants with recurrent wheezing.Methods From February 2015 to August 2016 in the General Hospital of Northern War Zone,outpatient department of Pediatrics treatment and hospitalization of age less than or equal to 3 year old children with recurrent wheezing,101 cases were induded as the research object.On the basis of asthma predictive index (API) score were divided into API positive group (n =55) and API negative group (n =46),according to the wheeze frequency of the two groups children were divided into 3 ～ 4 times wheezing groups and more than 5 times.Select 37 cases of healthy children as control group.The concentration of FeNO and blood EOS count are detected in all the children.The correlation between the three groups of children with FeNO concentration,the correlation between FeNO and blood EOS count,the correlation between the the frequency of wheeze and FeNO in experimental groups were analyzed.Results (1) API positive group mean FeNO (19.3 ± 6.2) ppb was significantly higher than API negative group (7.7 ± 2.9) ppb,there was no difference (P ＞ 0.05).API negative group mean FeNO (7.7 ± 2.9) ppb is lower than the normal control group (9.5 ± 2.0) ppb,there was no difference (P ＞0.05).(2) API positive group mean EOS count (124.7 ± 1.6) x 106/L is higher than API negative group (86.1 ± 1.9) x 106/L,there was significant difference (P ＜ 0.01);(3) There was a correlation between FeNO level and blood EOS count in API positive group,there was no correlation between FeNO level and blood EOS count in API negative group and con~ol group.(4) No statistical differences were found in ≤4 times wheezing groups and more than 5 times of the mean FeNO.Conclusion There is no significant difference in the mean value of FeNO between different times of wheezing in children with recurrent wheezing.The combination of medical history,EOS,FeNO and API might be used to predict the wheezing episode of infants.

Objective:To examine the plasma soluble interleukin 2 receptor (sIL-2R)and the expression of IFN-γR in helper T (Th)cells in peripheral blood of patients with recurrent oral ulcer(ROU).Methods:The peripheral blood was obtained from 21 pa-tients in active stage of ROU and 21 healthy controls.Flow cytometry was used to detect the quantity of IFN-γR in CD +4 T cells,ELISA was used to detect the level of sIL-2R.Results:The expression of IFN-γR in CD +4 T cells and sIL-2R content in plasma of the patients with ROU were significantly higher than those in the healthy controls(P <0.05).Conclusion:Over expression of IFN-γR in CD +4 T cells and sIL-2R in peripheral blood may be related to the genesis of ROU.