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海南医科大学学报（英文版）
海南医科大学学报（英文版）

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海南医科大学学报（英文版）/Journal Journal of Hainan Medical University
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    Effect of Qinggan Huayu granule on H22 liver ascitic tumor mice

    Fei-Ya SuoXiao-Ran ZhuZhen-Huan YangShu-Kun Yao...
    1-7页
    查看更多>>摘要：Objective: To evaluate the therapeutic effect of Qinggan Huayu granule on mice with H22 liver cancer ascites tumor. Methods: A H22 liver cancer ascites mouse model was established by intraperitoneally injecting H22 liver cancer cells. Mice were randomly divided into the model group, the Ganfule group (1.35 g/kg), the fluorouracil group (50 mg/kg i.p), the Qinggan Huayu granule groups at low(0.67 g/kg), medium (1.34 g/kg), and high (2.68 g/kg) doses. Then the mice were administered continuously for 10 days and body weight and abdominal circumference were monitored every 3 days. On day 11, eight rats in each group were randomly selected for dissection to detect the amount of peritoneal water, peritoneal permeability and histopathological changes. The remaining mice were observed for survival. In addition, the vascular endothelial growth factor A (VEGFA) and vascular endothelial growth factor receptor 2 (VEGFR2) were determined by Western blotting. Results: Compared with the model group, the weight growth of mice in the fluorouracil group and the medium-dose and high-dose Qinggan Huayu granule groups was slower (P < 0.05). Moreover, the abdominal circumference of mice in each treatment group was increased slowly. There were significant differences in abdominal circumference between the fluorouracil group, the medium-dose group and the control group from day 6 (P < 0.05) while the abdominal circumference of the high dose group was significantly smaller than that of the control group from day 12 (P < 0.05). Moreover, compared with the model group, the amount of ascites in the medium- and high-dose Qinggan Huayu granule groups was decreased significantly (P < 0.05). The optical density value of ascites supernatant in medium- and high-dose Qinggan Huayu granule group and the fluorouracil group decreased significantly (P < 0.05) and the survival period of the medium-dose Qinggan Huayu granule group and the fluorouracil group was prolonged prominently (P < 0.05). There was no significant difference in the low-dose Qinggan Huayu granule group and the Ganfule group. Peritoneal histopathological assay showed more complete peritoneal structure, less edema and less angiogenesis of the peritoneum in the fluorouracil group and the medium- and high-dose Qinggan Huayu granule group, which was better than that of the Ganfule group and the low-dose group. Compared with the model group, the expressions of VEGFA and VEGFR2 in the medium-dose Qinggan Huayu granule group decreased significantly (P < 0.05, P < 0.01). Conclusion: Qinggan Huayu granule can inhibit ascites production in the mice model with H22 liver cancer ascites tumor, prolong the survival of mice, and reduce peritoneal permeability and suppress the increase of peritoneal neovascularization. The mechanism may be related to the inhibition of VEGF /VEGFR pathway.
      原文链接:
    • NETL
    • NSTL
    • 万方数据
    • 维普

    Establishment and evaluation of a mouse model of affective disorder combined with atherosclerosis

    Shuang GengFeng-Rong WangShuai WangFan-Yu He...
    8-13页
    查看更多>>摘要：Objective: To establish a mouse model of affective disorder complicated with atherosclerosis (AS) by high fat feeding and chronic mild unpredictable stimulation (CUMS), and to provide an animal model for the later study of the prevention and treatment of affective disorder complicated with atherosclerosis by traditional Chinese medicine. Methods: 10 C57BL /6J mice were used as blank group, and 20 ApoE-/- mice were randomly divided into AS group and AS+CUMS group. After one week of adaptive feeding, except for the blank group, the other two groups were fed with high fat diet. Meanwhile, the AS+CUMS group was given chronic unpredictable mild stress. The model was evaluated after 16 weeks of modeling. During the experiment, the body weight, food intake, excitability, hair color and other general morphology of mice in each group were observed and recorded. Behavioral indexes (Sucrose preference tests and Open Field test) were detected in each group.The levels of 5-hydroxytryptamine (5-HT) and hypothalamic-pituitary-adrenal (HPA) axis hormones, including adrenocorticotropin (ACTH) and corticosterone (CORT), were detected by ELISA. Serum lipid levels, including total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C), were detected by ELISA. HE staining was used to observe the pathological condition of aorta. Results: Compared with blank group, the excitability and food intake of AS+CUMS group were significantly decreased. There were no significant differences in sugar water consumption and activity capacity of mice in AS group, while sugar water consumption and activity capacity of mice in AS+CUMS group were significantly decreased (P < 0.01). The serum 5-HT levels in AS group and AS+CUMS group were decreased, and the levels of ACTH and CORT in AS+CUMS group were significantly decreased (P < 0.01), and the levels of ACTH and CORT in AS+CUMS group were significantly increased (P < 0.01). The serum TC, TG and LDL-C levels of mice in AS group and AS+CUMS group were significantly increased (P < 0.01), while the HDL-C level of mice in both groups was significantly decreased (P < 0.01). HE staining results showed that the area and degree of plaques in the active vascular lumen of AS group and AS+CUMS group were larger and heavier. Conclusion: High fat feeding combined with CUMS was successful in establishing a mouse model of emotional disorder combined with atherosclerosis.
      原文链接:
    • NETL
    • NSTL
    • 万方数据
    • 维普

    Chlorogenic acid modulates glucose and lipid metabolisms via AMPK activation in HepG2 cells and shows its anti-hyperglycemic effect on streptozocin-induced diabetic mice

    Hong-Ji YaoZhao-Yi XueRui-Qi WangCheng-Zuo Jiang...
    14-21页
    查看更多>>摘要：Objective: In this study, we focus on the hypoglycemic effects of chlorogenic acid (CGA) in vitro and in vivo and its mechanism base on regulate glucose and lipid metabolism via AMPK activation. Methods: The cytotoxicity, glucose consumption and intracellular triglyceride assay were been detected by commercial kits. The western blots were used to detection the associated protein levels after CGA treatment, and the inhibiter blocking experiments were also be done. In vivo experiment, the fasting blood-glucose, lipid metabolism, liver function, insulin resistance, glucose tolerance, and pathological change were assessed on streptozocin induced diabetic mice. Results: We found that CGA exhibited no cytotoxicity at concentrations of 100μM, it caused a significant increasing of glucose consumption and reducing of the PA-BSA induced intracellular TG level on HepG2 cells at 50μM and 100μM treatment, CGA exhibited up-regulating the level of p-AMPK (Thr172) and p-ACC (Ser79) in dose-dependent manners in vitro and in vivo. The stimulating activities of CGA on AMPK were completely blocked by compound c (CC) on HepG2 cells. And the efficacies of CGA on glucose consumption and intracellular TG accumulation were also completely blocked by CC pretreatment. The CGA also exhibited potent anti-diabetic effects with hypoglycemic activity, improve insulin resistance and glucose tolerance, regulate glucose and lipid metabolism and protect the liver function in vivo. Conclusion: Our results suggested that CGA can regulate glucose and lipid metabolism by AMPK activation, and exhibit potent anti-hyperglycemic effect in streptozocin induced diabetes mice, and may be used as a potential effective anti-diabetes drug.
      原文链接:
    • NETL
    • NSTL
    • 万方数据
    • 维普

    The relationship between Metrnl and diabetic cardiomyopathy and its related molecular mechanism

    Min ZhangRui-Lin DingFeng JiangQing Peng...
    22-27页
    查看更多>>摘要：Objective: To investigate the changes of serum concentration of Metrnl in diabetic cardiomyopathy mice, and the relationship between Metrnl and Diabetic cardiomyopathy(DCM) and its molecular mechanism.Methods: Fifteen male mice were randomly divided into experimental group(DCM+Metrnl),model group(DCM)and control group.Metrnl concentration was measured with an enzyme-linked immunosorbent assay.The experimental group was treated with Metrnl,and the control group and model group were treated with equal volume solvent.Then the myocardial pathological changes,reactive oxygen species and the expression of PPARs and GLUT4 protein and the expression of CD36 and SOD gene were observed after 7 days of administration of recombinant Metrnl.Results: Serum Metrnl concentrations were elevated in DCM(P>0.05).Metrnl reduced the serum concentrations of total cholesterol(TG,P<0.05),triglyceride(TC,P<0.05)and low density lipoprotein cholesterol(LDL-C,P<0.05),while increased high density lipoprotein cholesterol(HDL-C,P<0.05)in DCM.In addition,Metrnl improved the energy metabolism of DCM,decreased the production of reactive oxygen species(ROS)and up-regulated the protein expressions of PPAR-a,PPAR-β/ ,GLUT4 and the expression of SOD in cardiomyocytes,while CD36 gene expression was down-regulated.Conclusion: Serum Metrnl concentrations were elevated in DCM mouse modles.Metrnl improved lipid metabolism and cardiac function in DCM. Besides,it can reduced myocardial oxidative stress injury through PPAR-β/ ,GLUT4 pathway.
      原文链接:
    • NETL
    • NSTL
    • 万方数据
    • 维普

    Mesenchymal stem cells promote the induction of colorectal cancer cells on normal intestinal epithelium

    Ying HuYi LiuCheng-Jiang WeiYa-Zhen Zhu...
    28-32页
    查看更多>>摘要：Objective: To establish a co-culture model of colon cancer cells or mesenchymal stem cells with normal colon epithelial cells in vitro for simulating the tumor microenvironment in vitro, and to investigate the effect of colon cancer cells or mesenchymal stem cells on the migration and epithelial-mesenchymal transformation (EMT) of normal colon epithelial cells in the co-culture environment. Method: Co-culture model of colon cancer cell line SW480 or human umbilical cord mesenchymal stem cells (hUC-MSCs) with human normal colon epithelial cells (NCM460) was established. Morphological changes of NCM460 after co-culture were evaluated by microscopic observation, and migration ability of NCM460 was measured by wound healing and Transwell assay. Meanwhile, Western blot was used to detect the EMT markers of NCM460. Results: There was no significant change in cell morphology of NCM460. Transwell assay results showed that when hUC-MSC or SW480 were co-cultured with NCM460, there is a trend of enhancement of the migration ability of NCM460, and the expression of Vimentin was up-regulated to some extent (P<0.05), E-cadherin and wound healing ability were not significantly changed (P>0.05).When NCM460 were cocultured with MSCs and SW480 at the same time, NCM460's wound healing ability and migration ability were significantly enhanced, meanwhile Vimentin protein expression was significantly up-regulated and E-cadherin protein was significantly down-regulated significantly (P<0.05). Conclusion: Colon cancer cells can increase the migration ability of normal colon epithelial cells and upregulate the expression of EMT markers. Mesenchymal stem cells may play a role in this process.
      原文链接:
    • NETL
    • NSTL
    • 万方数据
    • 维普

    Meta-analysis of clinical efficacy and safety of kidney Tonifying therapy in the treatment of interstitial lung disease

    Ning ZhangShi-Yan YanYa-Li GuoFei Pan...
    33页
    查看更多>>摘要：Objective: To evaluate the efficacy and safety of kidney tonifying therapy in the treatment of Interstitial Lung Disease(ILD). Methods: We searched Wanfang Data, CNKI, CBM, VIP, Pub Med, EMBASE, Web of science and Cochrane Library for Randomized Controlled Trials (RCTs) of kidney tonifying therapy in the treatment of ILD. The retrieval time was from the establishment of the database to December 15, 2020. Rev man 5.3 software was used to analyze and summarize the collected literature, and the methodological quality of the included studies was evaluated by the bias risk assessment scale of Cochrane Collaboration Network. Results: A total of 15 articles with 1045 patients were included.The results of meta-analysis showed that compared with the control group treated with conventional western medicine alone, kidney tonifying therapy or combined with conventional western medicine was beneficial to improve the clinical total effective rate [RR = 1.33 (95％ CI 1.24-1.43),P<0.00001]. At the same time, compared with the control group treated with routine western medicine, kidney tonifying therapy or combined with routine western medicine can improve cough and wheezing symptoms of patients [MD = - 0.62 (95％ CI - 0.78 ～ - 0.46),P<0.00001] and MD = - 0.79 (95％ CI - 0.18 ～ - 0.49),P<0.00001]. However, there was no significant improvement in 6-minute walk test and lung function (DLCO％)(P>0.05); only one study reported 7 patients with adverse reactions, but after corresponding treatment, the symptoms were significantly relieved. The analysis of the characteristics of intervention measures in the treatment group showed that there were a total of 80 traditional Chinese medicines involved, of which Shu Dihuang appeared the most frequently, and the tonic drugs were used the most. The two meridians of the lung and kidney appear most frequently. Among the four qi and five flavors, warm and sweet medicines have the highest frequency. Conclusion: Adopting kidney-tonifying method or combined with conventional Western medicine treatment can improve the total clinical effectiveness of patients.Adopting kidney-tonifying method or combined with conventional Western medicine treatment to improve symptoms such as coughing and wheezing. No serious adverse reactions have been reported, and the safety is reliable.Due to the low quality of the included literature, the results of this study need to be verified by high-quality, large sample randomized controlled trials.
      原文链接:
    • NETL
    • NSTL
    • 万方数据
    • 维普

    Meta analysis of efficacy and safety of traditional Chinese medicine combined with hydroxychloroquine sulfate in the treatment of Sjogren's syndrome

    Shu-Xia HuangTian-Yu CaoZhan-Shuo XiaoHai-Bo Yin...
    34-40页
    查看更多>>摘要：Objective: To systematically evaluate the efficacy and safety of traditional Chinese medicine combined with hydroxychloroquine sulfate in the treatment of Sjogren's Syndrome(SS). Methods: Two researchers searched the databases of Chinese National Knowledge Infrastructure(CNKI), Wanfang Database,Weipu Database, Chinese Biomedical Literature Database, PubMed Database, Web of science Database and The Cochrane Library Database(the retrieval period is from the establishment of the database to October 2020) and screened the literatures independently.The data were extracted for bias risk assessment, and then meta-analysis was performed using Revman 5.3 software. Results: A total of 19 articles involving 1185 patients were included, including 617 cases in the treatment group and 568 cases in the control group. Combined data analysis showed that the total effective rate of traditional Chinese medicine combined with hydroxychloroquine sulfate in the treatment of Sjogren's syndrome was significantly higher than that of hydroxychloroquine sulfate alone [R R=1.34,95％CI(1.24,1.44),P<0.00001].The improvement of salivary gland[SMD=0.66,95％CI (0.47,0.85),P<0.00001], tear secretion function [MD=2.56,95％CI(1.29,3.83),P<0.0001] and reducing CRP[MD=-3.53,95％CI(-3.93,-3.14),P<0.00001], ESR [MD=-5.80,95％CI(-8.48,-3.13),P<0.00001]were better than those of the control group. However, there was no significant difference in the reduction of IgG and the incidence of adverse reactions between the two groups. Conclusion: Traditional Chinese medicine combined with hydroxychloroquine sulfate in the treatment of SS is superior to the control group in total effective rate, improvement of salivary gland and tear secretion function, and reduction of CRP and ESR, and we didn't see the significantly increase on the adverse event.However, due to the small sample size and low quality of the included studies, the conclusion needs to be verified by larger sample and higher quality randomized controlled trials.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    Analysis of the mechanism of Radix Astragali-Radix Pseudostellariae in the treatment of chronic heart failure based on network pharmacology

    Mei-Hui ChenYu-Bo HanYan-Bo SuiLi Liu...
    41-47页
    查看更多>>摘要：Objective: To explore and analyze the effective component, target and mechanism of action of Radix Astragali-Radix Pseudostellariae in the treatment of chronic heart failure (CHF) by network pharmacological research methods. Methods: With the help of TCMSP database, the effective chemical constituents and targets of Radix Astragali-Radix Pseudostellariae were screened out, and CHF-related proteins were obtained by Gene Cards and OMIM database. The target protein interaction network (PPI) was constructed on the String database platform, and using DAVID database to conduct the GO function and KEGG pathway enrichment analysis on the target of the obtained astragalus-pseudostellariae for the treatment of CHF. Results: Radix Astragali-Radix Pseudostellariae were selected as 28 effective chemical components and 104 therapeutic targets for CHF. There were obtained 49 GO functional annotations and 86 KEGG signaling pathways. Conclusion: Radix Astragali-Radix Pseudostellariae can treat CHF through multi-target and multi-pathway.
      原文链接:
    • NETL
    • NSTL
    • 万方数据
    • 维普

    Revealing the material basis of MMP9-mediated activating blood and removing blood stasis drugs on Danshen-Ligusticum chuanxiong anti-vascular effect

    Li-Li HouHai-Xin LiuQing-Shan Li
    48-55页
    查看更多>>摘要：Objective: Reveal the material basis and mechanism of angiogenesis effect of Danshen-chuanxiong herb-partners. Methods: The effective components of Danshen and chuanxiong were searched in the TCM System Pharmacology Database (TCMSP), and the drug targets were searched in the Swiss Target Prediction database; in the Disease-Gene Database (DisGeNET) ) Search for angiogenesis-promoting and inhibiting angiogenesis targets; use the protein interaction database (STRING) database and Cytoscape software to analyze the network core targets; use the DAVID database to enrich the drug-disease target intersection for GO and KEGG; RT-qPCR experiments verified the effect of luteolin on MMP9 gene expression; in vitro tube formation experiments analyzed the effect of luteolin on endothelial cell neovascularization. Results: After analysis, it is concluded that Danshen has 10 active ingredients and 50 angiogenesis targets; Chuanxiong has 2 active ingredients and 4 angiogenesis targets. The intersection of drug-taking targets yielded 9 targets, including AR, PARP1, MMP9, MMP2, MMP12, AKR1B10, ABCC1, CDK6, and STAT3.After analyzing the active ingredient-target network graph of Danshen/Chuanxiong, it was concluded that luteolin is the key chemical ingredient. After protein interaction (PPI) analysis, the results showed that MMP9 is the core target. The KEGG pathway is mainly enriched in 5 signaling pathways, the most important pathway is cancer-related pathways. There are 22 main biological processes of GO, which mainly involve collagen catabolism, protein extracellular matrix, metal endopeptidase activity, etc. The preliminary analysis of tubule formation experiment shows that luteolin inhibits angiogenesis and down-regulates the expression of MMP9 gene. Conclusion : Luteolin, the key chemical component of the Danshen-Ligusticum chuanxiong drug pair, inhibits angiogenesis by regulating the MMP9 target, and develops the reverse regulation of angiogenesis for the traditional Chinese medicine for promoting blood circulation and removing blood stasis on the basis of the known treatment of ischemic diseases. Provide a new perspective and theoretical basis for the use of Danshen and Chuanxiong medicine in clinical cancer patients. Reveal the material basis and mechanism of angiogenesis effect of Danshen-chuanxiong herb-partners.
      原文链接:
    • NETL
    • NSTL
    • 万方数据

    Mechanism of action and targeted therapy of stellate cells in liver fibrosis

    Sheng-Lan ZengRong-Zhen ZhangNa WangTing-Shuai Wang...
    56-59页
    查看更多>>摘要：The incidence of liver fibrosis is increasing worldwide, and if left untreated, it will later develop into cirrhosis with a high mortality rate. In this paper, the activation pathway and related mechanism of stellate cells in liver fibrosis are introduced, and some current therapeutic methods are summarized. These results suggest that stellate cells play an important role in liver fibrosis, and targeted therapy for the purpose of inhibiting the activation of stellate cells and inducing their apoptosis is expected to be an effective regimen to reverse liver fibrosis. However, there are some problems such as insufficient in-depth study of related mechanisms and imperfect experiments. In future animal experiments and clinical trials, more studies can be carried out to provide high-quality protocols for the treatment of liver fibrosis.
      原文链接:
    • NETL
    • NSTL
    • 万方数据
    • 维普