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Aim To verify the role of Shengjiang Powder in sepsis and explore its molecular mechanism. Methods The targets of drug active ingredients and disease-related targets were searched by TCMSP, Disgenet and other databases, and the intersection of the two was selected. DAVID database was used to carry out enrichment analysis of GO and KEGG pathways for intersection targets, and molecular docking was performed between drug active ingredients and core genes of key pathways. Mouse model of sepsis was constructed by cecal ligation puncture (CLP). Spleen tissue and serum of mice were collected. The percentage of T cell subsets in spleen was detected by flow cytometry, and IL-6 and IL-10 levels in serum were detected by ELISA. Results A total of 25 active ingredients, 238 targets of active ingredients, 2797 disease-related targets, 90 genes of intersection between active ingredients and disease-related targets, potential targets were AKT, JUN, EGFR, MMP9, etc. GO enrichment analysis showed 1021 items, including 942 biological processes, 23 cell compositions and 55 molecular functions. KEGG pathway analysis found that the intersection genes were mainly enriched in THE PD-1/PD-L1 signaling pathway, HIF-1 signaling pathway, TNF signaling pathway and inflammatory mediators signaling pathway, indicating that the therapeutic effect may be related to these pathways. The molecular docking results showed that quercetin, kamanol, emodin and other core compounds could be well combined with key genes. Flow cytometry results showed that after seven days of CLP, the proportion of CD4 T cells in spleen decreased, the proportion of CD4 PD-1 T cells increased, the release of IL-6 decreased, the content of IL-10 increased, and the mice were immunosuppressed. The percentage of CD4 T cells in spleen increased, the number of CD4 PD-1 T cells decreased, the release of IL-6 was enhanced, the content of IL-10 decreased, and the immunosuppression was improved. Conclusions It is proved that Shengjiang Powder can increase the release of pro-inflammatory cytokine IL-6, increase the ratio of CD4 T/CD8 T cells, and decrease the expression of anti-inflammatory cytokine IL-10 in the late stage of sepsis, so as to improve immune suppression in the late stage of sepsis and improve the survival rate of mice.
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AIM:To observe the expression of microRNA-126-5p during myocardial injury and its role in myo-cardial cell injury induced by adriamycin(also called doxorubicin, DOX).METHODS: The BALB/c mouse model of DOX-induced acute and chronic myocardial injury was established via intraperitoneal injection of DOX.HE staining was applied to observe the morphological changes of myocardial tissues.Lactate dehydrogenase(LDH)in serum was detected and PowerLab system was used to detect the influence of DOX on the changes of ±dp/dtmax.The expression of microRNA-126-5p in injured myocardial tissues and the H 9c2 cells exposed to DOX was detected by real-time PCR.Gain-and loss-of-function experiments were conducted to detect the role of microRNA-126-5p in H9c2 cells treated with DOX on LDH release and caspase-3 activation.RESULTS:In acute and chronic DOX myocardial damage models in mice,HE staining showed disarranged myocardial fibers, dissolved myofibril and inflammatory cell infiltration.Higher serum LDH level and lower ±dp/dtmaxin DOX-treated mice than those in normal mice were found.Compared with the normal mice, the expression level of microRNA-126-5p was significant increased in the myocardium with DOX-induced injury.Similarly,the expression level of microRNA-126-5p was significant increased in the H9c2 cells treated with DOX.In addition, over-expression of microRNA-126-5p decreased cell viability and promoted apoptosis,while microRNA-126-5p ablation promoted the viability and inhibited the apoptosis of H9c2 cells.CONCLUSION:The microRNA-126-5p expression is up-regulated in myocar-dial injury induced by DOX,and microRNA-126-5p inhibits cell viability and promotes apoptosis induced by DOX.
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<p><b>OBJECTIVE</b>To explore the mechanism of Jiantai liquid on the endometrium development of embryo implantation dysfunction mice.</p><p><b>METHOD</b>The model of embryo implantation dysfunction mice was induced by mifepristone and treated by Jiantai liquid. All animals were sacrificed on day 8 of pregnancy. Estradiol and progesterone concentrations in serum and endometrium tissue homogenates were measured by radioimmunoassay method, the endometial expressions of estrogen receptor (ER)and progesterone receptor (PR)assessed by immunohistochemical SP method.</p><p><b>RESULT</b>There were no significantly differences in the estradiol and progesterone concentrations in serum and uterus tissue homogenates among three groups( P > 0.05). Absorbency and area rate of ER, PR in model group' s gland and stroma were higher than those in model group(P < 0.05), which was similar with the control group( P > 0.05).</p><p><b>CONCLUSION</b>Jiantai liquid increase the implantation rate and improve the endometrial development by increasing the expressions of ER, PR in endometrium of embryo implantation dysfunction</p>
Subject(s)
Animals , Female , Male , Mice , Astragalus propinquus , Chemistry , Drug Combinations , Drugs, Chinese Herbal , Pharmacology , Embryo Implantation, Delayed , Endometrium , Metabolism , Loranthaceae , Chemistry , Mifepristone , Pharmacology , Plants, Medicinal , Chemistry , Receptors, Estrogen , Metabolism , Receptors, Progesterone , Metabolism , Salvia miltiorrhiza , ChemistryABSTRACT
<p><b>OBJECTIVE</b>To explore the effect of Jiantaiye (JTY) on the expression of estrogen receptor (ER) and ER mRNA in uterus of mice with embryo implantation dysfunction.</p><p><b>METHODS</b>Embryo implantation dysfunction mouse models were induced with mifepristone and treated with JTY. All animals were sacrificed on day 8 of pregnancy. The endometrial ER and ER mRNA expressions were assessed by immunnohistochemical SP method and semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>Area ratio and absorbency of ER in the JTY treated group's gland and stroma were higher than those of the model group, quite similar to those of the normal control's, and ER mRNA expression in treated group's uterus was significantly higher than that in the models, but it was not significantly different from the normal control.</p><p><b>CONCLUSION</b>JTY improves the endometrial development by increasing ER and ER mRNA expressions of uterus of mice with embryo implantation dysfunction.</p>
Subject(s)
Animals , Female , Male , Mice , Pregnancy , Drugs, Chinese Herbal , Pharmacology , Embryo Implantation , Endometrium , Metabolism , Immunohistochemistry , Methods , Mice, Inbred Strains , RNA, Messenger , Metabolism , Receptors, Estrogen , Genetics , Metabolism , Staining and Labeling , Tissue Distribution , Uterine Diseases , Allergy and Immunology , Uterus , Allergy and ImmunologyABSTRACT
<p><b>OBJECTIVE</b>To explore the molecular mechanism of jiantai liquid (JTL) in improving endometrial receptivity of mice with embryo implantation dysfunction (EID).</p><p><b>METHODS</b>Mice model of EID induced by mifepristone were intervened with JTL (Twig of Chinese Taxillus, Red Sage root, Chinese Angelica, Milkvetch root, Chuanxiong rhizome), and sacrificed on day 8 of pregnancy. The endometrial estrogen receptor (ER) and progesterone receptor (PR) protein and their gene expressions were assessed by Western blot and semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>Levels of ER and PR protein and their gene expressions in the JTL treated group were significantly higher than those in the model group respectively (all P < 0.05), and showed insignificant difference from those in the normal control group (all P > 0.05).</p><p><b>CONCLUSION</b>JTL could promote the development of endometrium and improve the embryo implantation by way of regulating the levels of ER and PR protein and gene expression in mice with EID.</p>