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1.
Article in Chinese | WPRIM | ID: wpr-879143

ABSTRACT

Pharmacology network was used to investigate the common key target and signaling pathway of Notoginseng Radix et Rhizoma in the protection against diabetic nephropathy(DN), diabetic encephalopathy(DE) and diabetic cardiomyopathy(DCM). The chemical components of Notoginseng Radix et Rhizoma were obtained through TCMSP database and literature mining, and SwissTargetPrediction database was used to predict potential targets of Notoginseng Radix et Rhizoma. The disease targets of DN, DE and DCM were obtained through OMIM and GeneCards databases. The overlapped targets of component targets and disease targets of DN, DE and DCM were obtained, and the network of "chemical component-target-disease" was established. The enriched GO and KEGG of the overlapped genes were investigated by using ClueGo plug-in with Cytoscape. At the same time, the PPI network was constructed through STRING database, and the common key targets for the treatment of three diseases by Notoginseng Radix et Rhizoma were obtained through topological parametric mathematical analysis by Cytoscape. A total of 166 chemical components and 835 component targets were screened out from Notoginseng Radix et Rhizoma. Briefly, 216, 194 and 230 disease targets of DN, DE and DCM were collected, respectively. And 54, 45 and 57 overlapped targets were identified when overlapping these disease targets with component targets of Notoginseng Radix et Rhizoma, respectively. Enrichment analysis indicated that the AGE-RAGE signaling pathway and FoxO signaling pathway were the common pathways in the protection of Notoginseng Radix et Rhizoma against DN, DE and DCM. Network analysis of the overlapped targets showed that TNF, STAT3, IL6, VEGFA, MAPK8, CASP3 and SIRT1 were identified as key targets of Notoginseng Radix et Rhizoma against DN, DE and DCM, the selected key targets were verified by literature review, and it was found that TNF, IL6, VEGFA, CASP3 and SIRT1 had been reported in the literature. In addition, there were the most compounds corresponding to the commom core target STAT3, indicating that more compounds in Notoginseng Radix et Rhizoma could regulate STAT3. This study indicated that Notoginseng Radix et Rhizoma potentially protected against DN, DE and DCM through regulating AGE-RAGE signaling pathway and FoxO signaling pathway and 7 common targets including TNF, STAT3, IL6, VEGFA, MAPK8, CASP3 and SIRT1. This study provided a reference for the research of "different diseases with same treatment" and also elucidated the potential mechanism of Notoginseng Radix et Rhizoma against DN, DE and DCM.


Subject(s)
Brain Diseases , Diabetes Mellitus , Diabetic Cardiomyopathies/genetics , Diabetic Nephropathies/genetics , Humans , Research Design , Signal Transduction
2.
Article in Chinese | WPRIM | ID: wpr-781465

ABSTRACT

OBJECTIVE@#To investigate the distribution of peripheral blood lymphocytes and natural killer (NK) cells, and its influence on the prognosis of patients with myelodysplastic syndromes (MDS).@*METHODS@#The lymphocytes proportion, absolute lymphocyte counts (ALC), NK cell proportion and absolute NK cell counts (ANKC) as well as the related data of 95 MDS patients diagnosed between 2013 and 2017 analyzed retrospectively. The correlation of ALC and ANKC with prognosis was also analyzed.@*RESULTS@#As compared with low ALC patients, MDS patients with ALC≥0.885×10/L had a higher overall response rate (66.7% vs 35.8%) (P<0.01). The ALC of effective patients after treatment significatitly increased in compaison of ALC at diagnosis. Multivariate analysis indicated that patients with ALC≥0.885×10/L had long overall survival (OS) time in comparison with patients with low level (16.4 vs 12.4 months) (P<0.05). The OS time of patients with ANKC≥0.110×10/L was shorter in comparison with patients with low level (10.9 vs 16.3 months) (P<0.01). Otherwise, blast, cytogenetic risks and treatment response were also independent risk factors of MDS (P<0.05). Revised International Prognostic Scoring System (IPSS-R) combined with ANKC could improve predictive accuracy of IPSS-R alone (AUC 0.718 vs 0.674) (P<0.05).@*CONCLUSION@#Lymphocytes and NK cells are important for the prognosis evaluation of MDS patients.

3.
Article in Chinese | WPRIM | ID: wpr-862678

ABSTRACT

Objective::Based on the protective effect of Guhong injection (GH) on cerebral ischemia, mechanism of GH against cerebral ischemia was identified using RNA-seq transcriptome and bioinformation analysis. Method::The model of middle cerebral artery occlusion (MCAO) was established through thread embolization. Sham group, model group, low-dose GH group (0.625 mL·kg-1·d-1), high-dose GH group (2.5 mL·kg-1·d-1), positive group (Ginaton, 8 mL·kg-1·d-1) were set up. Ludmila Belayev 12-point scoring method was applied to assess the protective effect of GH against MCAO-induced cerebral ischemia. And the differentially expressed genes after treatment with GH were identified by RNA-Seq technology. Enrichment analysis, cluster analysis and association analysis on disease targets of cerebral ischemia were carried out through such databases as DAVID, String and The Human Phenotype Ontology. Finally, the regulatory network was constructed by Cytoscape3.4.0. Result::Compared with the sham group, the neurological impairment was obvious in the model group (P<0.01), and the neurological impairment was alleviated in the GH group compared with the model group (P<0.05). RNA-Seq technology analysis showed that GH regulated genes involving such biological processes as cell apoptosis, inflammation, oxidative stress, toll-like signaling pathway and mitogen-activated protein kinase (MAPK) signaling pathway. Twenty disease targets and 64 MAPK signaling pathway genes were associated with differentially expressed genes after GH treatment, in which 23 genes were involved in apoptosis and inflammation. Conclusion::GH protected against cerebral ischemia in many ways, among which MAPK signaling pathway is an important way to exert its effect in inhibiting apoptosis and inflammation.

4.
Acupuncture Research ; (6): 202-208, 2020.
Article in Chinese | WPRIM | ID: wpr-844181

ABSTRACT

OBJECTIVE: To explore the mechanism of electroacupuncture (EA) underlying improvement of cerebral infarction (CI) by investigating its influence on expression of cerebral Wnt7a, lymphoid enhancer factor-1 (LEF1), glycogen synthase kinase 3β(GSK-3β) and Dickkopf-1(DKK1) mRNA and proteins in CI rats. METHODS: A total of 280 male Wistar rats were randomly divided into blank control (n=10), sham-operation, model and EA groups,and 90 rats of the last 3 groups were further divided into 1, 3, 6, 9, 12 and 24 h, and 3, 7 and 12 d subgroups with 10 rats in each subgroup. The CI model was established by occlusion of the middle cerebral artery (MCAO). The sham-operation group received the same surgical operation but without thread embolus insertion. EA (2 Hz/15 Hz, 2 mA) was applied to "Shuigou" (GV26) for 20 min, once a day for 1, 3, 7 and 12 d, respectively. The neurological deficit was evaluated by using Neurological Severity Scores (NSS). The expression levels of Wnt7a,LEF1, GSK-3β and DKK1 mRNAs and proteins in the right ischemic brain tissues were detected by Quantative real-time PCR and Western blot, respectively. RESULTS: After MCAO, the NSS score was significantly increased in the model and EA groups relevant to the blank control and sham-operation groups (P0.05). CONCLUSION: EA of GV26 can significantly improve the neurological deficit symptoms in MCAO rats, which may be associated with its effects in up-regulating the expression of Wnt7a and LEF1 mRNAs and proteins, and in down-regulating the expression of GSK-3β and DKK1 mRNAs and proteins.

5.
Journal of Medical Postgraduates ; (12): 720-725, 2020.
Article in Chinese | WPRIM | ID: wpr-822590

ABSTRACT

ObjectiveAt present, there are relatively few studies on the inhibitory effect of ursolic acid (UA) on the proliferation of thyroid cancer cells. This paper intends to explore the inhibitory effect and mechanism of ursolic acid on the proliferation of TPC-1 cells in thyroid papillary carcinoma.MethodsAfter adhering TPC-1 cells to the wall, the original medium was discarded and added ursolic acid medium without fetal bovine serum (0, 2, 4, 8, 16, 32 μmol/L, respectively, with 0 μmol/L as the control), and then the culture medium without cells was used as blank. The proliferation inhibition rate of TPC-1 cells was detected by CCK8 reagent at different times (24 h, 48 h); Flow cytometry was used to detect the apoptosis rate; JC1 kit was used to detect the changes of mitochondrial membrane potential (MMP) of TPC-1 cells after ursolic acid was applied; Fluorescent probe DCFH-DA was used to detect reactive oxygen species in TPC-1 cells after ursolic acid intervention; Flow cytometry was used to detect the protein expression of survivin and vascular endothelial growth factor (VEGF) in cells. RT-PCR assay detected the expression of survivin and VEGF mRNA in TPC-1 cells after the intervention of ursolic acid at different concentrations.ResultsThe inhibitory rate of 2, 4, 8, 16 and 32 mol/L ursolic acid on TPC-1 cells was significantly higher than that of 0 mol/L (P<0.01), and the inhibitory rate of 48 h ursolic acid on TPC-1 cells was significantly higher than that of 24 h (P<0.05). Therefore, the TPC-1 cell inhibition rate was positively correlated with ursolic acid concentration and the time (P<0.05). The apoptosis rates of 0 mol/L, 4 mol/L and 8 mol/L ursolic acid were (4.13±0.61)%, (6.53±0.65)% and (13.13±1.59)%, respectively. With the increase of the concentration, the apoptosis rate of TPC-1 cells increased gradually (P<0.05). The relative expression levels of survivin, VEGF protein and mRNA of 4 and 8 mol/L ursolic acid were significantly lower than those of 0 mol/L (P<0.05), and the expression levels of 8 mol/L ursolic acid was significantly lower than that of 4 mol/L (P<0.05).ConclusionUrsolic acid can effectively inhibit the proliferation and induce the apoptosis of TPC-1 cells, and its inhibitory induction pathway is related to the expression of survivin and VEGF in cells.

6.
Article in Chinese | WPRIM | ID: wpr-828037

ABSTRACT

To observe the efficacy of San'ao Decoction(SAD) in diffusing the lung and relieving asthma, and its intervention effect on the expression of transient receptor potential V2(TRPV2) during alleviating asthma, this study replicated an ovalbumin(OVA)-induced asthmatic mice model, and investigated the intervention effect of SAD on the airway inflammation and airway hyperresponsiveness. The regulatory mechanisms of SAD on the mRNA and protein expressions of TRPV2 in lung tissues and the levels of interleukin-4(IL-4),-10(IL-10), nerve growth factor(NGF), prostaglandin D_2(PGD_2) in bronchoalveolar lavage fluid(BALF) were discussed. Compared with the control group, the model group showed typical asthmatic phenotype, the level of eosinophils(EOS) in peripheral blood and BALF as well as the airway hyperresponsiveness were increased(P<0.01), and pathological damage in lung tissue was serious. The mRNA and protein expressions of TRPV2 in lung tissue were increased significantly, while the levels of IL-4, IL-10, NGF and PGD_2 in BALF were elevated(P<0.05,P<0.01). SAD could relieve bronchial asthma manifested as repaired lung patholo-gical changes(P<0.05), reduce the level of EOS in blood and BALF(P<0.05, P<0.01), and improve pulmonary resistance and lung compliance(P<0.05, P<0.01). SAD could also regulate the inflammatory cytokine levels of IL-4, IL-10, NGF, PGD_2 in BALF, and reduce the gene and protein expression of TRPV2 in the lung tissue(P<0.05, P<0.01). It is verified that SAD could reduce the lung inflammation, and improve lung function in asthmatic mice. The regulatory mechanism of SAD on asthma induced by OVA might be related to the regulation of TRPV2 expression and the induced decrease of Th2-related cytokines and neuropeptides, which provides the evidences for the treatment of asthma with SAD.


Subject(s)
Animals , Asthma , Bronchoalveolar Lavage Fluid , Calcium Channels , Disease Models, Animal , Drugs, Chinese Herbal , Lung , Mice , Mice, Inbred BALB C , Ovalbumin , TRPV Cation Channels
7.
Article in Chinese | WPRIM | ID: wpr-828017

ABSTRACT

Ischemic stroke is the most common form of stroke and one of the main diseases leading to death and disability in the world. Its pathological process is complex and changeable as a result of the interaction of multiple pathological links, such as oxidative stress, apoptosis and inflammation. Traditional Chinese medicine Notoginseng Radix et Rhizoma is the dried roots and rhizomes of Panax notoginseng. In clinic, it is mainly used for the treatment of diseases of cardio-cerebral system and vascular system. Recent studies have shown that total saponins of P. notoginseng, the main active ingredients of P. notoginseng against cerebral ischemia, are complex, and can interfere with the enzyme-promoted cascade reaction through multiple pathways, multiple links and multiple targets, so as to exert its physiological effect. Therefore, it has become a hotspot in studies for prevention and treatment of cerebral ischemia. At present, a great advance has been made in studies on the mechanism of anti-cerebral ischemia of P. notoginseng saponins, but more in-depth studies are needed because of its complex mechanism. Therefore, in this paper, a total of 165 kinds of P. notoginseng saponins were summarized, and simply divided into protopanaxadiol saponins(55 species), protopanaxadiol saponins(37 species) and special structural type saponins(73 species) according to their structural types, so as to provide reference for further studies of P. notoginseng saponins. In addition, the effect of P. notoginseng on cerebral ischemia is clear, but its mechanism remains to be further explored. This paper summarizes the mechanism of P. notoginseng saponins against cerebral ischemia in five aspects: antioxidant stress, reduction of apoptosis, reduction of inflammatory reaction, inhibition of calcium overload and protection of blood-brain barrier. Four kinds of drugs commonly used in the treatment of cerebral ischemia were summarized, in order to provide a theoretical basis for further development and utilization of P. notoginseng saponins in the treatment of cerebral ischemia.


Subject(s)
Brain Ischemia , Cerebral Infarction , Humans , Panax notoginseng , Rhizome , Saponins
8.
Article in English | WPRIM | ID: wpr-773408

ABSTRACT

OBJECTIVE@#To investigate the molecular mechanisms of the adverse effects of exposure to sulfamonomethoxin (SMM) in pregnancy on the neurobehavioral development of male offspring.@*METHODS@#Pregnant mice were randomly divided into four groups: control- (normal saline), low- [10 mg/(kg•day)], middle- [50 mg/(kg•day)], and high-dose [200 mg/(kg•day)] groups, which received SMM by gavage daily during gestational days 1-18. We measured the levels of short-chain fatty acids (SCFAs) in feces from dams and male pups. Furthermore, we analyzed the mRNA and protein levels of genes involved in the mammalian target of rapamycin (mTOR) pathway in the hippocampus of male pups by RT-PCR or Western blotting.@*RESULTS@#Fecal SCFA concentrations were significantly decreased in dams. Moreover, the production of individual fecal SCFAs was unbalanced, with a tendency for an increased level of total fecal SCFAs in male pups on postnatal day (PND) 22 and 56. Furthermore, the phosphatidylinositol 3-kinase (PI3k)/protein kinase B (AKT)/mTOR or mTOR/ribosomal protein S6 kinase 1 (S6K1)/4EBP1 signaling pathway was continuously upregulated until PND 56 in male offspring. In addition, the expression of Sepiapterin Reductase (SPR), a potential target of mTOR, was inhibited.@*CONCLUSION@#In utero exposure to SMM, persistent upregulation of the hippocampal mTOR pathway related to dysfunction of the gut (SCFA)-brain axis may contribute to cognitive deficits in male offspring.


Subject(s)
Alcohol Oxidoreductases , Metabolism , Animals , Anti-Infective Agents , Toxicity , Fatty Acids, Volatile , Feces , Chemistry , Female , Hippocampus , Metabolism , Male , Memory , Mice, Inbred ICR , Pregnancy , Prenatal Exposure Delayed Effects , Sulfamonomethoxine , Toxicity , TOR Serine-Threonine Kinases , Metabolism
9.
Article in Chinese | WPRIM | ID: wpr-773120

ABSTRACT

Chemical constituents of the Fufang Huangbai Ye( FFHB) were analyzed and identified by UPLC-ESI-LTQ-OrbitrapMS. The analysis was performed on an Waters HSS T3 reverse phase column( 2. 1 mm×100 mm,1. 8 μm). The mobile phase consisting of 0. 1% aqueous formic acid( A) and acetonitrile( B) was used with gradient elution,and the flow rate was 0. 3 mL·min~(-1).Based on the information of the accurate mass,the multistage fragment ions,the mass spectrometric data of the standard substance and the relative reference literature,the structure of the chemical constituents in FFHB were identified. Based on the identified compounds,network pharmacology study,including target prediction,functional enrichment,and molecular docking was applied to screen out the main active substances for treatment of diabetes foot and explore the potential mechanism. The results showed that a total of 138 compounds were identified,including 28 alkaloids,16 flavonoids,11 phenylethanoid glycosides,9 cycloolefins,11 cyclohexylethanol derivatives,28 phenolic acids and derivatives,3 lignans,4 terpenes,28 volatile oils and the others. Further,36 active substances for diabetes foot were screened out,and the functional enrichment showed the potential mechanism of FFHB were mainly seven functional items including inflammatory response,growth factor activity. This study combining the UPLC-LTQ-Orbitrap-MS technology and the network pharmacology provide a useful reference and basis for active compounds,quality control markers and the pharmacological mechanism of FFHB for diabetic foot treatment.


Subject(s)
Chromatography, High Pressure Liquid , Diabetic Foot , Drug Therapy , Drugs, Chinese Herbal , Pharmacology , Humans , Mass Spectrometry , Molecular Docking Simulation , Phytochemicals , Pharmacology
10.
Article in Chinese | WPRIM | ID: wpr-775927

ABSTRACT

OBJECTIVE@#To select the optimized treatment plan of acupuncture for lateral femoral cutaneous neuritis by using multiple indexes decision-making method based on the clinical evidence.@*METHODS@#The randomized control trials (RCTs) regarding acupuncture for lateral femoral cutaneous neuritis in the CNKI database, CBM database, WANFANG database, VIP database, PubMed, Cochrane Library and Embase published before December 31, 2017 were comprehensively collected. The modified Jadad scale was used to evaluate the quality of the RCTs. Then the evaluation indexes were selected and the dimensions of evaluation indexes were standardized by using extreme difference transformation method. The weight of each index was determined by using relative comparison method and the standardized matrix was weighted. Thus, the ideal solution and the negative ideal solution were obtained, and the relatively degree of each treatment plan to the ideal solution was calculated to propose the optimized plan of acupuncture for lateral femoral cutaneous neuritis.@*RESULTS@#A total of 18 RCTs were included, the optimized plan of acupuncture for lateral femoral cutaneous neuritis was using thin fire needle to rapidly prick the abnormal skin region with fast needle insertion-withdrawal technique; the fire needle was applied repeatedly; intensive pricking to form a treatment area; the treatment was given once every 5 days.@*CONCLUSION@#Based on the current clinical evidence, the optimized plan of acupuncture for lateral femoral cutaneous neuritis is using thin fire needle to prick the abnormal skin region; the multiple methods of plum-blossom needling met the characteristic of lateral femoral cutaneous neuritis and is suitable for clinical selection. The main acupoints are points in the abnormal skin area or the acupoints in the foot- meridian and foot- meridian, combined with lumbar Jiaji (EX-B2) points.


Subject(s)
Acupuncture Therapy , Humans , Meridians , Needles , Neuritis , Therapeutics , Randomized Controlled Trials as Topic
11.
Article in Chinese | WPRIM | ID: wpr-802355

ABSTRACT

The clinical value is the core factor for determining the products of Chinese patent medicines on the market. It is clear that defining the clinical positioning of Chinese patent medicines and maximizing their clinical efficacy and value are of great practical significance for each Chinese patent medicine. Precise clinical positioning not only requires systematic analysis and summarization of existing literature and clinical practice data, but also requires verification and proof from detailed experimental data, thus to provide scientific support for basic research. In this research, a three-dimensional integration strategy of " traditional Chinese medicine (TCM) theory-clinical practice-basic research" was proposed to play a vital role in clinical positioning and evaluation of Chinese patent medicines. Yixinshu capsule was taken as an example to discuss clinical positioning of Chinese patent medicines under the guidance of TCM theory. Based on the interpretation of the evolution of the pathogenesis of coronary heart disease (thoracic obstruction), combined with the core efficacy of the drug composition, the effect of Yixinshu capsule in benefiting Zongqi, calming midnd, improving blood circulation and eliminating blood stasis was identified, which was suitable for treatment for the recurrent episodes of angina pectoris, and emergency of symptoms of chronic heart failure. At the level of TCM theory, the clinical positioning of Yixinshu capsule was further defined, and the key points of in-depth research were proposed to provide reference for the mechanism research and clinical application of Yixinshu capsule. Based on the prescription and its score functions, precise analysis of clinical positioning of large varieties of TCM under the guidance of TCM theory, on the one hand will give full play to the value of TCM original knowledge and guide the basic research of Chinese patent medicines, on the other hand the research results will enrich, benefit and sublimate the TCM theory, and finally provide a critical paradigmatic for the clinical positioning of large varieties of TCM under the guidance of TCM theory.

12.
Article in Chinese | WPRIM | ID: wpr-802023

ABSTRACT

Quality marker(Q-marker) is a new concept and pattern for quality control of traditional Chinese medicine(TCM),which will lead the development direction for quality control of TCM.Among them,how to characterize the overall quality attribute of TCM and its biological effect,is a critical scientific problem in the study of Q-marker.In this paper,integrated pharmacology is utilized to screen out and confirm the Q-marker from the complex system of TCM,so as to solve the critical scientific problem.System biology in vivo is firstly applied to establish the correlation of chemical fingerprints of TCM,their metabolic fingerprints,network targets,biological effects and efficacy of TCM,which is used to preliminary screen out Q-marker of TCM.Following that,a pharmacological method in vitro,including intestinal absorption in vitro coupled with bioactivity assessment,is employed to simultaneously determine the absorbed doses of TCM and evaluate their biological activity.Furthermore,data mining is utilized to establish the exact quantitative mathematic model between Q-marker of TCM and bioactivity.Meanwhile,two representative examples,including Yuanhu Zhitong tablets,Xinsuning capsules,are introduced to identify Q-marker of TCM and establish their quality standards related with bioactivity,which will be beneficial to improve the level of quality control of TCM and ensure the effectiveness and safety of clinical applications.

13.
Article in Chinese | WPRIM | ID: wpr-773771

ABSTRACT

OBJECTIVE@#To investigate the effect of Yiqi Wenyang Huoxue Huatan Fang (YWHHF) on alleviating hypoxia-hypercarbia pulmonary hypertension by inhibiting endothelial-mesenchymal transition (EndoMT) BMP-7/Smads pathway.@*METHODS@#Fifty male healthy SD rats of clean grede, weighting (180~220) g, were randomly divided into 5 groups (=10):normoxia group (N), hypoxia-hypercarbia group (HH); YWHHF high dose group (YH), middle dose group (YM) and low dose group (YL). The rats in N group were kept in normal oxygen environment, the remaining four groups were intermittently exposed to hypoxia-hypercarbia environment (9%~11% O, 5%~6% CO) for 4 weeks, 6 days a week, 8 hours per day. The rats in YH, YM, YL groups were received YWHHF gavage in a dosageof 0.6, 0.3, 0.15g/kg respectively (3 ml/kg),the rats in N and HH groups were received equal volume of normal saline. After 4 weeks, the mean pulmonary arterial pressure(mPAP) was detected,the right ventricular free wall and left ventricle plus ventricular septum were isolated to determine the right ventricular hypertrophy index. Lung ultrastructural changes were surveyed under an electronic microscopy, the changes of pulmonary artery structure surveyed by immunofluorescence, the mRNA levels of alpha-smooth muscle actin (α-SMA)、platelet endothelial cell adhesion molecule-1 (CD31)、bone morphogenetic protein-7 (BMP-7)、drosophila mothers against decapentaplegic protein1/5/8 (Smad1/5/8) were detected by RT-PCR, and the protein levels of α-SMA、CD31、BMP-7、p-Smad1/5/8 and Smad1/5/8 were detected by Western blot.@*RESULTS@#Compared with N group, mPAP and the right ventricular hypertrophy index were increased,some significant injuries also were discovered under microscopic observation,the mRNA and protein expression of α-SMA was increased, and the mRNA expressions of CD31、BMP-7、Smad1/5/8 were decreased in the other four groups, the protein expressions of CD31、BMP-7、p-Smad1/5/8 were decreased(<0.05). Compared with HH group, the above changes in YH、YM、YL groups were all improved (<0.05).@*CONCLUSIONS@#YWHHF can inhibit EndoMT to alleviate pulmonary hypertension, and the mechanism may be related to the promotion of the expression of BMP-7/Smads pathway.


Subject(s)
Animals , Hypercapnia , Hypertension, Pulmonary , Hypoxia , Male , Pulmonary Artery , Rats , Rats, Sprague-Dawley
14.
Article in Chinese | WPRIM | ID: wpr-773750

ABSTRACT

OBJECTIVE@#To observe the pulmonary vascular remodeling in rats with pulmonary hypertension induced by hypoxia and hypercapnia, and to explore the role of endoplasmic reticulum stress in pulmonary hypertension.@*METHODS@#Forty SD rats were random-ly divided into four groups:normoxic control group (N), hypoxia hypercapnia group (HH), ERS inhibitor 4-phenylbutyric acid group (4-PBA), endoplasmic reticulum stress (ERS) pathway agonist tunicamycin group (TM), ten rats in each group.The mean pulmona-ry artery pressure (mPAP), mean carotid artery pressure (mCAP) and right ventricular hypertrophy index of rats in each group were measured.Pulmonary artery smooth muscle cells were identified by immunofluorescence α-smooth muscle actin (α-SMA).Morphologi-cal changes of lung tissue and pulmonary artery were observed by electron microscope.The apoptotic index of pulmonary artery smooth muscle cells in each group was detected by TUNEL.Reverse transcription polymerase chain reaction (RT-PCR) and Western blot were used to detect the expression of glucose-regulated protein (GRP78), C/EBP homologous protein (CHOP), c-Jun N-terminal kinase (JNK) and cysteinyl aspartate specific proteinase-12 (caspase-12) mRNA and protein in each group.@*RESULTS@#①Compared with the N group, the mPAP, the ratio of right ventricle weight to left ventricle plus ventricular septum weight[RV/(LV+S)]and the ratio of pulmonary artery wall area to total tube area (WA/TA) were increased (<0.01), and the ratio of pulmonary artery luminal area to total tube area (LA/TA) were decreased (<0.01), pulmonary artery smooth muscle cell apoptosis index were decreased (<0.05 or <0.01) in HH group, 4-PBA group and TM group.ERS related protein and mRNA expressions were increased, the differences were statistically significant.②Compared with the HH group, the mPAP, [RV/(LV+S)]and WA/TA of 4-PBA group were decreased ( <0.01), LA/TA and pulmonary artery smooth muscle cell apoptosis index were increased (<0.01, <0.05).The expressions of ERS related protein and mRNA were all decreased (<0.05 or <0.01).③Compared with the HH group, the mPAP, [RV/(LV+S)]and WA/TA of TM group were increased (<0.05 or <0.01), pulmonary artery middle layer thickened, LA/TA and pulmonary artery smooth muscle cell apoptotic index were decreased (<0.01).ERS related protein and mRNA expressions were increased with statistical significance except GRP78 protein.@*CONCLUSIONS@#Pulmonary vascular remodeling in rats with pulmonary hypertension induced by hypoxia and hypercapnia may be related to the excessive proliferation of pulmonary artery smooth muscle cells and too little apopto-sis;ERS related factors (JNK, caspase-12 and CHOP) are involved in the regulation of pulmonary hypertension induced by hypoxia hypercapnia.


Subject(s)
Animals , Endoplasmic Reticulum Stress , Hypercapnia , Hypertension, Pulmonary , Hypoxia , Pulmonary Artery , Rats , Rats, Sprague-Dawley
15.
Chinese Journal of Immunology ; (12): 25-30, 2018.
Article in Chinese | WPRIM | ID: wpr-702667

ABSTRACT

Objective:To analyze the effects of BANCR on proliferation,apoptosis,invasion and angiogenesis in human hepatocarcinoma cell line HepG2.Methods:The expression of BANCR was detected by quantitative real-time reverse transcription PCR (qRT-PCR).BANCR siRNA and Scramble was respectively transfected into human hepatocarcinoma cell line HepG2.Cell proliferation was detected by CCK-8.Flow cytometry was performed to analyze the apoptosis.Transwell assay was used to test the invasion.Angiogenesis was analyse by tube formation assay.Western blot was executed to check the expression of proliferating cell nuclear antigen (PCNA),caspase-3,matrix metalloprotein 9 (MMP-9),vascular endothelial growth factor(VEGF),acidic fibroblast growth factor (bFGF)and interferon-γ (IFN-γ).Results:The expression of BANCR in HepG2 was higher than L02 (P<0.05).Compared with control group,the cell proliferation folds in BANCR siRNA was largely decreased.Besides,BANCR siRNA group had a higher apoptosis rate and less invasive cells (P<0.05).Western blot showed that the expression level of caspase-3 and IFN-γwas obviously enhanced in BANCR siRNA group,and the expression of PCNA,MMP-9,Fn,Vimentin,VEGF and bFGF was distinctly surpressed in BANCR siRNA group compared to control group (P < 0.05).Conclusion:siRNA interference of BANCR promotes apoptosis and represses proliferation,invasion and angiogenesis in human hepatocarcinoma cell line HepG2.

16.
Article in Chinese | WPRIM | ID: wpr-690712

ABSTRACT

In this study, a computer-based network pharmacology approach was applied to investigate the potential mechanism and important components of Rhodiola crenulata in the protection of H9c2 cells against hydrogen peroxide (H₂O₂)-induced oxidative stress. The intestinal absorption liquid of R. crenulata enhanced the cell viability, maintained cell morphology and inhibited cell apoptosis in the H₂O₂-induced oxidative stress in H9c2. Then, computer-based network pharmacology was used to analyze the relevant mechanism. A total of 133 oxidative stress-related compounds were screened out; and 26 of them occupied the top 20%, and all of the compounds enriched in 43 oxidative stress-related key targets. Finally, a "compound-target-pathway-function" network was constructed. Based on the analysis of the network pharmacology, R. crenulata protected H9c2 cells against H₂O₂-induced oxidative stress probably by affecting apoptosis-related processes, such as cell death, nitric oxide metabolism, oxidative stress, mitochondrial mechanism, redox process, redox-related enzyme activty and other oxidative stress-related process. And salidroside, ethyl gallate and catechins, which were the main components of R. crenulata, played an important role in this process. Therefore, the potential mechanism and important components of R. crenulata revealed the protective effect on oxidative stress. This study shows a multi-component, multi-target and overall regulation effect of R. crenulata on the oxidative stress, and provides a reliable reference for subsequent systematic experimental studies for the pharmacodynamic material foundation and mechanism of action R. crenulata.

17.
Article in Chinese | WPRIM | ID: wpr-701152

ABSTRACT

AIM:To investigate the relationship between transforming growth factor-β(TGF-β)/Smads signa-ling pathway and pulmonary arterial endothelial-mesenchymal transition(EndoMT)in hypoxia-hypercapnia pulmonary hy-pertension(HHPH)process and the regulatory effect of Yiqi-Wenyang-Huoxue-Huatan formula(YWHHF).METHODS:Healthy male SD rats were randomly divided into 5 groups:normal control(N)group,hypoxia-hypercapnia(HH)group, high-dose YWHHF(YH)group,middle-dose YWHHF(YM)group and low-dose YWHHF(YL)group.The rats in N group was housed in normoxic environment,and the rats in the other 4 groups were housed in hypoxia-hypercapnia environ-ment(9%~11%O2and 5%~6%CO2)for 4 weeks,8 h/d,6 d/week.The excess water vapor was absorbed by anhy-drous CaCl2,and CO2was absorbed by sodium hydroxide.The rats in YWHHF groups were put into the oxygen chamber before the same volume of YWHHF at different concentrations were given(200 g/L for YH group,100 g/L for YM group and 50 g/L for YL group).The average pulmonary artery pressure and the average carotid artery pressure were measured during the operation.After operation,the right ventricular free wall and left ventricle plus interventricular septum were col -lected for determining the right ventricular hypertrophy index.Moreover,the morphological changes of the lung tissues were observed under light microscope.The mRNA and protein levels of α-smooth muscle actin(α-SMA),CD31,TGF-β1 and Smad2/3,and the protein level of p-Smad2/3 were detected by RT-PCR and Western blot.RESULTS:Compared with N group,the pulmonary artery mean pressure,the mRNA and protein expression of α-SMA,TGF-β1 and Smad2/3,and the protein level of p-Smad2/3 were increased, the levels of CD31 were decreased(P<0.05), and the lung tissue damage was observed in the other 4 groups.Compared with HH group,the pulmonary artery mean pressure,the mRNA and protein expression of α-SMA,TGF-β1 and Smad2/3,and the protein level of p-Smad2/3 were decreased, while the mRNA and protein levels of CD31 were increased.Moreover,the lung tissue damage was reduced in YH,YM and YL groups.CON-CLUSION:TGF-β/Smads pathway may be involved in the process of EndoMT under hypoxia and hypercapnia condition, and YWHHF may reduce EndoMT by inhibiting the expression of TGF-β/Smads pathway-related molecules.

18.
Tianjin Medical Journal ; (12): 585-589, 2018.
Article in Chinese | WPRIM | ID: wpr-698072

ABSTRACT

Objective To investigate the degrees of injury severity of sepsis models made by different kinds of Escherichia coli. Methods The 152 mice were randomly divided into control group, DH5α group, 44102 group, and 25922 group, with 38 rats in each group. DH5α group, 44102 group and 25922 group were intraperitoneally injected with 300 μL of Escherichia coli DH5α, 44102 and 25922 at the concentration of 1.0 × 109CFU/kg to prepare sepsis models of different kinds of Escherichia coli. Control group was injected intraperitoneally with the same amount of normal saline. (1) After 8 h, four mice were taken from each group for peripheral blood bacterial culture . (2) After 12 h, ten mice in each group were used for measuring serum levels of TNF-α and IL-6 by enzyme-linked immunosorbent assay (ELISA). (3) Western blot assay was used to determine the serum levels of high-mobility group protein (HMGB1) in four mice of each group. (4) Ten mice in each group were used to measure serum levels of alanine transaminase (ALT), aspartate aminotransferase (AST), creatinine (CR) and blood urea nitrogen (BUN) by automatic biochemical analyzer. (5) After liver, lung and kidney tissues were fixed with formaldehyde, hematoxylin-eosin (HE) staining was performed (n=10 for each group). Results In DH5α group, 44102 group and 25922 group, bacteria, inflammatory cytokines TNF-α, IL-6 and HMGB1 protein, liver and kidney indicators ALT, AST, CR and BUN showed a sequential increasing trend (P<0.01). The severe degrees of alveolar structure damage, hepatic cell infiltration and renal glomerular atrophy were DH5α group, 44102 group and 25922 group in turn. There were no obvious damages of lung, liver or kidney tissues in control group. Conclusion Escherichia coli 25922 induces severe sepsis injury and can be used to study the animal models of the initial inflammatory phase of sepsis. Escherichia coli 44102 induces moderate damage of sepsis and can be used in animal models that do not require definitive sepsis staging experiments. Escherichia coli DH5α induces less damage of sepsis and can be used to explore immunosuppressive therapy of the animal model of sepsis.

19.
Article in Chinese | WPRIM | ID: wpr-695628

ABSTRACT

Objective· To study the effects of fenvalerate exposure during puberty on oxidative stress in rat testis.Methods· Fifty male Sprague-Dawley (SD) rats were randomly divided into the control group (corn oil),low dose group (0.02 mg/kg fenvalerate),moderate dose group (1 mg/kg fenvalerate),high dose group (50 mg/kg fenvalerate) and intervention group (50 mg/kg fenvalerate+100 mg/kg N-acetyl-L-cysteine),ten rats for each group,for two months by gavage at four weeks of age.Malondialdehyde (MDA) content,activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) in testis and testicular tissue morphology were detected.Results· Compared with the control group,the rat body weight and activities of GSH-Px and SOD in testis were significantly decreased in high dose group while MDA content was increased (all P<0.05).Compared with the high dose group,MDA content was decreased and GSH-Px activity was increased in the intervention group (both P<0.05).The results of testicular histology showed that with the increasing exposure dose,the spermatogenic cells were arranged loosely,the number of layers was decreased and the inner diameter of seminiferous tubules was increased.Conclusion· Exposure to fenvalerate during puberty may induce oxidative damage in testis tissue of male rats.

20.
Chinese Medical Journal ; (24): 920-926, 2018.
Article in English | WPRIM | ID: wpr-687008

ABSTRACT

<p><b>Background</b>Compared with full-term infants, very preterm infants are more vulnerable to injury and long-term disability and are at high risk of death. The predictive value of ultrasound and imaging on the neurodevelopment is one of the hot topics. This study aimed to investigate the relationship between cranial ultrasound (cUS) variables and neurodevelopmental outcomes of very preterm infants.</p><p><b>Methods</b>Totally 129 very preterm infants (gestational age ≤28 weeks) in neonatal intensive care unit of Hunan Children's Hospital between January 2012 and November 2014 were included in this retrospective study. Serial cUS (weekly before discharge and monthly after discharge) was performed on the infants until 6 months or older. Magnetic resonance imaging (MRI) was performed on the infants at approximately the term-equivalent age. The mental developmental index (MDI) and psychomotor developmental index (PDI) were followed up until the infants were 24 months or older. The relationship between brain injury and MDI/PDI scores was analyzed.</p><p><b>Results</b>The consistency rate between cUS and MRI was 88%. At the first cUS, germinal matrix hemorrhage (GMH) Grades 3 and 4, hospitalization duration, and weight are significantly correlated with MDI/PDI and prognosis (MDI: odds ratio [OR] = 8.415, 0.982, and 0.042, P = 0.016, 0.000, and 0.004; PDI: OR = 7.149, 0.978, and 0.012, P = 0.025, 0.000, and 0.000, respectively). At the last cUS, gestational age, extensive cystic periventricular leukomalacia (c-PVL), and moderate and severe hydrocephaly are significantly correlated with MDI (OR = 0.292, 60.220, and 170.375, P = 0.004, 0.003, and 0.000, respectively). Extensive c-PVL and moderate and severe hydrocephaly are significantly correlated with PDI (OR = 76.861 and 116.746, P = 0.003 and 0.000, respectively).</p><p><b>Conclusions</b>Very premature infants with GMH Grades 3 and 4, short hospitalization duration, and low weight have low survival rates and poorly developed brain nerves. Cerebral palsy can result from severe cerebral hemorrhage, moderate and severe hydrocephaly, and extensive c-PVL. The sustained, inhomogeneous echogenicity of white matter may suggest subtle brain injury.</p>


Subject(s)
Brain , Diagnostic Imaging , Brain Injuries , Diagnostic Imaging , Cerebral Hemorrhage , Diagnostic Imaging , Echoencephalography , Female , Gestational Age , Humans , Hydrocephalus , Diagnostic Imaging , Infant, Premature , Infant, Premature, Diseases , Diagnostic Imaging , Magnetic Resonance Imaging , Pregnancy , Retrospective Studies
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