Improvement effect of ligustilide on rats with heart failure by regulating PKD1/HIF-1α/VEGF pathway / 吉林大学学报(医学版)

Objective:To discuss the effect of ligustilide on the cardiac function and angiogenesis in the rats with heart failure,and to clarify its regulatory effect on protein kinase D1(PKD1)/hypoxia-inducible factor-1α(HIF-1α)/vascular endothelial growth factor(VEGF)pathway.Methods:The SD rats were randomly divided into sham operation group,model group,ligustilide group,PKD1/HIF-1α/VEGF signaling pathway inhibitor CID755673(CID)group,and ligustilide+CID group.The heart failure rat model was established by ligation of the left anterior descending coronary artery.The rats in ligustilide group were injected intravenously with 20 mg·kg-1 ligustilide,the rats in CID group were injected intraperitoneally with 50 mg·kg-1 CID,and the rats in ligustilide+CID group were injected intraperitoneally with 50 mg·kg-1 CID followed by intravenous injection of 20 mg·kg-1 ligustilide,once per day for 4 consecutive weeks.The cardiac function indexes of the rats in various groups were detected by echocardiography;the percentages of myocardial infarction areas of the rats in various groups were detected by 2,3,5-triphenyltetrazolium chloride(TTC)staining;the pathomorphology of myocardium tissue of the rats in various groups was observed by HE staining;the expression levels of PKD1,HIF-1α,CD31,and VEGF mRNA and proteins in ischemic area of myocardium tissue of the rats in various groups were detected by real-time fluorescence quantitative PCR(RT-qPCR)and Western blotting methods.Results:Compared with sham operation group,the rats in model group and CID group had altered myocardial cell morphology,increased intercellular gaps,disorganized arrangement,visible muscle fiber breaks and inflammatory cell infiltration;the rats in ligustilide group and ligustilide+CID group had relatively orderly myocardial fiber arrangement,fewer myocardial fiber breaks and decreased number of inflammatory cells.Compared with sham operation group,the left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)of the rats in model group were decreased(P<0.05),the left ventricular end-systolic diameter(LVESD)and left ventricular end-diastolic diameter(LVEDD)were increased(P<0.05),and the expression levels of PKD1,HIF-1α,CD31,and VEGF mRNA and proteins in myocardium tissue were decreased(P<0.05).Compared with model group,the LVEF and LVFS of the rats in ligustilide group were increased(P<0.05),the LVESD and LVEDD were decreased(P<0.05),the percentage of myocardium infarction area was decreased(P<0.05),and the expression levels of PKD1,HIF-1α,CD31,and VEGF mRNA and proteins in myocardium tissue were increased(P<0.05);compared with model group,the LVEF and LVFS of the rats in CID group were decreased(P<0.05),the LVESD and LVEDD were increased(P<0.05),the percentage of myocardium infarction area was increased(P<0.05),and the expression levels of PKD1,HIF-1α,CD31,and VEGF mRNA and proteins in myocardium tissue were decreased(P<0.05);compared with ligustilide group,the LVEF and LVFS of the rats in ligustilide+CID group were decreased(P<0.05),the LVESD and LVEDD were increased(P<0.05),the percentage of myocardium infarction area was increased(P<0.05),and the expression levels of PKD1,HIF-1α,CD31,and VEGF mRNA and proteins in myocardium tissue were decreased(P<0.05);compared with CID group,the LVEF and LVFS of the rats in ligustilide+CID group were increased(P<0.05),the LVESD and LVEDD were decreased(P<0.05),the percentage of myocardium infarction area was decreased(P<0.05),and the expression levels of PKD1,HIF-1α,CD31,and VEGF mRNA and proteins in myocardium tissue were increased(P<0.05).Conclusion:Ligustilide can promote the angiogenesis,reduce the myocardium infarction area,and improve the cardiac function in the rats with heart failure;it works through activation of the PKD1/HIF-1α/VEGF pathway.

Yes-associated protein ameliorates tumor necrosis factor-α-induced epithelial barrier dysfunction by affecting the F-actin / 中国小儿急救医学

Objective:To investigate the protective role of Yes-associated protein(YAP)in intestinal epithelial barrier injury.Methods:The intestinal epithelial barrier model was established by culturing human colorectal adenocarcinoma cell line Caco-2 cells, which were divided into four groups: control group, Caco-2 monolayers did not receive any treatment; recombinant human tumor necrosis factor-α(rhTNF-α)group, 100 μg/L of rhTNF-α was added to Caco-2 monolayers; vector+ rhTNF-α group, Caco-2 monolayers were first added with control plasmid pcDNA3.1-vector, and 100 μg/L rhTNF-α was added 24 hours later; YAP+ rhTNF-α group, Caco-2 cells with barrier construction were first added with pcDNA3.1-YAP, and 100 μg/L rhTNF-α was added 24 hours later.Realtime-PCR and Western blot were used to evaluate YAP mRNA and protein expression level.Epithelial permeability was assayed by trans-epithelial electrical resistance(TEER)and fluorescein isothiocyanate-dextran 40(FD-40 flu). Cellular distribution of F-actin was assayed by immunofluorescence staining.Results:Compared with control group[(607.3±29.3)Ω·cm 2], TEER of rhTNF-α group[(265.3±32.7)Ω·cm 2] decreased, while TEER of YAP+ rhTNF-α group[(387.0±18.7)Ω·cm 2]increased compared with rhTNF-α group, the differences were statistically significant( P<0.001). The FD-40 flux of rhTNF-α(22.7%±0.5%) group was higher than that of the control group(6.3%±0.9%), while the FD-40 flux of Yap + rhTNF-α group(12.2%±0.8%) was lower than that of rhTNF-α group, the differences were statistically significant( P<0.001). Immunofluorescence staining showed that compared with the control group, the cytoskeletal F-actin fiber dense spot decreased in rhTNF-α group, and some cells showed obvious trans-cellular stress fiber structure, while the peripheral actin band was clear in YAP+ rhTNF-α group, and the intracellular stress fiber decreased.YAP+ TNF-α group appeared as a clear, peripheral actin ribbon with a decrease in cytoplasmic stress fibres. Conclusion:YAP overexpression significantly inhibits TNF-α induced decline of TEER, and increases of FD-40 flux and F-actin rearrangement of Caco-2.YAP could ameliorate TNF-α induced intestinal epithelial barrier injury by regulating cytoskeleton F-actin.

Advances in the treatment of infantile cholestatic hepatopathy / 国际儿科学杂志

Cholestatic hepatopathy is a hepatobiliary system disease caused by abnormal bile excretion.It is common in infants.And its incidence varies with region and cause.The incidence of cholestatic jaundice in full-term infants is about 1/2 500.The etiology of infantile cholestatic hepatopathy involves many factors including abnormal liver or bile ducts structure, genetic metabolic diseases, infections, endocrine diseases and parenteral nutrition-associated cholestasis.The disease needs to be treated according to the primary disease.If there is a clear etiology, etiological treatment is necessary.Usually symptomatic and comprehensive treatment is adopted due to inconclusive diagnosis.The artical mainly states the present therapy methods.

Clinical observation for low-dose azithromycin with tiotropium bromide in the treatment of stable chronic obstructive pulmonary disease / 中国综合临床

Objective To study the efficacy and safety of low-dose azithromycin with tiotropium bromide in the treatment of stable chronic obstructive pulmonary disease.Methods A hundred and ten patients were randomized into three groups:tiotropium bromide group (36 cases,group A),azithromycin with tiotropium bromide group(38 cases,group B)and control group(36 cases,group C).Patients in group A were given tiotropium bromide (18 μg,q,d )in addition to conventional treatment.The patients in group B were given lowdose azithromycin (250 mg,twice a week) in combined with tiotropium bromide.The patients in control group were given the conventional treatment only.The courses of treatment lasted for six months.Results Compared with the control group,the frequency of acute exacerbation in patients treated with azithromycin and tiotropium bromide was reduced remarkably ( 2.1 ± 0.6 and 4.9 ± 0.7,t =18.5061,P ＜ 0.05 ).The severity of clinic symptoms ( Cough 1.3 ± 0.5 vs.2.2 ± 0.6,P ＜ 0.05 ),expectoration ( 1.0 ± 0.2 vs.1.7 ± 0.3,P ＜ 0.05 ),anhelation ( 1.5 ± 0.8 vs.2.1 ± 0.6,t =3.6342,P ＜ 0.001 ) ],life quality ( 29 ± 8 vs.42 ± 11,P ＜ 0.05 ) and six-minutes walking distance( [ 370.00 ± 14.26 ] m vs.[ 290.00 ± 12.85 ] m,P ＜ 0.05 ) of the azithromycin with tiotropium bromide group were improved significantly when compared with control.Compared with the tiotropium bromide group,the frequency of acute exacerbation ( 2.1 ± 0.6 vs.3.2 ± 0.8,P ＜ 0.05 ),the severity of clinic symptoms (Cough 1.3 ±0.5 vs.1.8 ±0.4,P＜0.05),expectoration( 1.0 ±0.2 vs.1.3 ±0.3,P ＜0.05) and anhelation( 1.5 ±0.8 vs.1.9 ± 0.6,P ＜ 0.05 ) ],life quality ( 29 ± 8 vs.36 ± 10,P ＜ 0.05 ) and six-minutes walking distance ( [ 370.00 ± 14.26 ] m vs.[ 330.00 ± 13.76 ] m,P ＜ 0.05 ) were improved over those of tiotropium bromide group.Conclusion The long-term low-dose azithromycin in combinned with tiotropium bromide is good and safe in treating stable COPD.Therefore,it is worth of further clinical evaluation.

To Explor the Legal Duty and Ethic of Hospital and Doctor in Premarital Check-up / 中国医学伦理学

Premarital check-up differ from the common medical treatment,also differs from the health prevention work. It is very necessary to explor the legal duty and ethics of the hospital and doctor premarital check-up .There is suggestion for the hospital and doctor, when they carry out the legal duty and ethic .They'd better check-up carefully, publicity education, table a proposal, protect the privacy, perfect the records and performs and check-up with good intentions etc. It should protect actually the parties concerned's legitimate interest.