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Endothelial progenitor cells (EPCs) play an important role in diabetic vascular complications. A large number of studies have revealed that some clinical antihyperglycemics can improve the complications of diabetes by regulating the function of EPCs. Metformin can improve EPCs function in diabetic patients by regulating oxidative stress level or downstream signaling pathway of adenosine monophosphate activated protein kinase; Pioglitazone can delay the aging of EPCs by regulating telomerase activity; acarbose, sitagliptin and insulin can promote the proliferation, migration and adhesion of EPCs. In addition to lowering blood glucose, the effects of antihyperglycemics on EPCs may also be one of the mechanisms to improve the complications of diabetes. This article reviews the research progress on the regulation of EPC proliferation and function by antihyperglycemics.
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Humans , Cell Movement/drug effects , Cells, Cultured , Endothelial Progenitor Cells/drug effects , Hypoglycemic Agents/pharmacology , Signal Transduction/drug effectsABSTRACT
Objective Cysteinyl leukotrienes are potent inflammatory mediators. Their actions are mediated by specific receptors,the CysLT receptors(CysLT1R and CysLT2R),which have been cloned and characterized. In this stud-y,we investigated the protective effects of the CysLTR antagonist Pranlukast and HAMI 3379 on global cerebral ischemia/reperfusion(CI/R)injury in gerbils and its underlying mechanisms. Methods The gerbil model of CI/R was established by bilateral common carotid artery occlusion for 10 min followed by 24 h reperfusion. Then the animals were equally ran-domized into four groups: sham, model, Pranlukast(0.1 mg/kg)and HAMI 3379(0.1 mg/kg)groups. The later two groups were treated with intraperitoneal injection of Pranlukast and HAMI 3379,respectively,once daily for 4 days before carotid artery occlusion,while the former two groups with saline only,all at 10 mL/kg. After 24 h reperfusion,neurologi-cal deficit scores were observed and the behavioral dysfunction was assessed. The neuron morphology of cerebral cortex and CA1 subregion of hippocampus were observed in brain sections stained with cresyl violet. The expression of autophagy-relat-ed proteins beclin-1 and LC3 in the homogenate of cerebral cortex and hippocampus were determined using western blotting analysis. The ultrastructure of autophagosomes in the CA1 subregion of hippocampus was observed by electron microscopy. Results Compared with the model group, Pranlukast and HAMI 3379 attenuated neurological deficits, improved the be-havioral dysfunction,inhibited the neuron injury and loss, decreased the expression of autophagy-related protein beclin-1 and LC3 and the number of autophagosomes. Conclusions cysteinyl Leukotriene receptor antagonist Pranlukast and HAMI 3379 can alleviate global cerebral ischemia/reperfusion injury in gerbils. The protective effects of Pranlukast and HAMI 3379 appear to be associated with the inhibition of autophagy.
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OBJECTIVE@#: To investigate the effects of cysteinyl leukotrienes receptor (CysLTR) antagonists on global cerebral ischemia/reperfusion (CI/R) injury in gerbils, and to explore its mechanism.@*METHODS@#: Totally 40 gerbils weighting 45-65 g were randomized into sham, saline, Pranlukast and HAMI 3379 groups with 10 animals in each. The CI/R model was established in gerbils by bilateral common carotid occlusion for 10 min followed by reperfusion. After ischemia, the CysLTR antagonists Pranlukast (0.1 mg/kg) and HAMI 3379 (0.1 mg/kg) were injected intraperitoneally for 5 consecutive days in the last two groups,while the former two groups were injected with saline only (10 mL/kg). After 24 h or 14 d reperfusion, neurological deficit score was evaluated and the behavioral dysfunction was assessed, respectively. And 14 d after reperfusion, the neuron morphology of cerebral cortex was observed in brain sections stained with Cresyl violet. In addition, the Iba-1 (microgila) and GFAP (astrocyte) positive cells in cerebral cortex were observed by using immunohistochemitry method.@*RESULTS@#: CI/R models were successfully established in 21 out of 30 gerbils with 7 in saline group, 6 in Pranlukast group, and 8 in HAMI 3379 group. Compared with saline group, Pranlukast and HAMI 3379 significantly attenuated neurological deficits, improved the behavioral function 24 h after reperfusion(all 0.05). In addition, Pranlukast and HAMI 3379 also inhibited the neuron loss and injury, suppressed microgila and astrocyte activation 14 d after reperfusion(all <0.01).@*CONCLUSIONS@#: CysLTR antagonists Pranlukast and HAMI 3379 have long-term neuroprotective effect on chronic brain injury induced by global cerebral ischemia/reperfusion in gerbils.
Subject(s)
Animals , Behavior, Animal , Brain Injury, Chronic , Drug Therapy , Brain Ischemia , Gerbillinae , Leukotriene Antagonists , Pharmacology , Therapeutic Uses , Neuroprotective Agents , Pharmacology , Therapeutic Uses , Random Allocation , Receptors, Leukotriene , Metabolism , Reperfusion Injury , Drug TherapyABSTRACT
Non-alcoholic fatty liver disease (NAFLD) has become one of the major metabolic diseases.In view of the defects of traditional animal models, this study was the first to establish the NAFLD model of Mongolian gerbil (Meriones unguiculatus) with simple feed formula which is similar to human (from simple fatty liver to steatohepatitis, fibrosis,Liver cirrhosis).This study discussed the mechanism of rapid fatty liver deposition in Mongolian gerbil, revealed its molecular mechanism,main regulatory target and network function of fatty liver susceptibility.We provide a new animal model of NAFLD with relatively clear background and less time-consuming for clinical treatment and new drug development.The theoretical and practical basis for the breeding of inbred strain NAFLD gerbil was established.
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Objective To investigate the method to isolate and culture hepatic stellate cells ( HSCs) for studying the cellular mechanisms of hepatic frbrosis.Methods HSCs were isolated by nycodenz density gradient centrifugation after the hepatocytes obtained from adult male gebils were digested with pronase, collagenase and DNase, infused via portal vein.The cell viability was determined by trypan blue exclusion test.The purity of HSCs was identified by detectingα-SMA, desmin immunohistochemical staining.Results The yield rate of HSCs was 0.5~1 ×107 per gerbil liver, and the cell viability was more than 90%.The percentage ofα-SMA-positive cells was more than 75%after 3 days primary culture and almost 100% cells were α-SMA and desmin positive in passage culture.Conclusion The successful protocol of primary culture of Mongolian gerbil HSC provide a technical support for research of relevant liver diseases and drug development in the future.
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<p><b>OBJECTIVE</b>To examine the spatiotemporal profiles and localization of CysLT1R, CysLT2R and GPR17 in mice with 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced Parkinson disease (PD).</p><p><b>METHODS</b>PD model was induced by subcutaneous injection of MPTP (25 mg/kg) for 5 d in adult male C57BL/6 mice. At d10 after MPTP injection, the expression and cellular localization of CysLT1R, CysLT2R and GPR17 in the substantia nigra were detected by immunohistochemistry and immunofluorescence.</p><p><b>RESULTS</b>CysLT1R, CysLT22 and GPR17 were normally localized in TH-positive dopaminergic neurons and microglia, while CysLT2R was also expressed in astrocytes. In dopaminergic neurons, approximately 91% co-expressed GPR17, 77% co-expressed CysLT1R and 52% co-expressed CysLT2R. Compared with the control group, TH-positive cells in the substantia nigra were significantly reduced in PD mice. CysLT1R, CysLT2R and GPR17-positive cells were significantly reduced; and CysLT1R, CysLT2R, GPR17-positive dopaminergic neurons were also significantly reduced in the PD group. In the striatum, both CysLT1R and GPR17 were normally expressed in neurons; whereas CysLT2R was expressed in astrocytes. In PD striatum, CysLT1R and GPR17-positive cells were decreased, but CysLT2R expression was significantly increased which mainly expressed in the proliferating astrocytes.</p><p><b>CONCLUSION</b>CysLT1R, CysLT2R and GPR17 may be involved in the MPTP-induced PD damage in mice.</p>
Subject(s)
Animals , Male , Mice , Brain , Metabolism , Disease Models, Animal , Mice, Inbred C57BL , Nerve Tissue Proteins , Metabolism , Parkinson Disease , Metabolism , Receptors, G-Protein-Coupled , Metabolism , Receptors, Leukotriene , MetabolismABSTRACT
Objective To observe Mongolian gerbil's reproducing performance and growth indexes of biology for guidance of development and use of laboratory anima1. Methods 200 gerbils produced by seed-parents with good reproductive capacity and body constitution were selected (females and males were 100 each).When 2.5~3.0 months old,one male and one female were cohabited randomly for a long period of time.Results Every embryo gave birth to 14 young gerbils at best and 1 gerbil at least.The total embryos was 455 and the total young gerbils was 3191. The average young gerbils of every embryo were 7.01,and every embryo gave mostly birth to 5~9 young gerbils,accounting for 79.34 percent of all the embryos. The shortest time between two embryos was 20 days and the longest time was 127 days,and mostly were 20~60 days,accounting for 72.16 percent of total. Conclusion The body weight,body length and tail length of Mongolian gerbils grow rapidly from birth to 4 months old. The differences between female and male was not significantly before delectation,and the in the growing time after delectation,the body weight,body length and tail length of male gerbils were all greater than those of female gerbils.
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Objective To study the changes of antioxidant on ZCLA Mongolian gerbils' sera within different growth period.Methods The gerbils at the age of 1 month,3 months and 24 months were used in the experiment,with each 16(half male and half female),and the sera were collected for determining the MDA,SOD and GSH-Px.Results At the age of 3 months,MDA was the lowest,but GSH-Px was the highest,while the SOD was ascending with growing.Conclusion The changes of GSH-Px showed the direct relation to MDA,while the changes of the SOD was irrespective to the changes of MDA.
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Objective: To observe the promoting blood circulation by removing blood stasis of Lubai Capsule(LBC)(Rhizoma Phragmitis, Radix Paeoniae Alba, Radix Saposhnikoviae, Flos Schizonepetae, etc.). Methods: Acute blood stasis rat models were established with swimming in iced water and sc adrenalin in order to observe the effect of LBC on blood rheology. Mesenteric microcirculatory disturbance rat models were also established with adrenalin in order to observe the effect of LBC. Clotting time was measured in vitro with prothrombin time(PT) and kaolin partial thromboplastin time(KPTT) kit in order to observe its effects. Results: LBC could decrease the whole blood and plasma viscosity, fibrinogen, erythrocyte sedimentation and aggregation ratio of blood platelets of rats, ease the sticky condition of blood stasis rat models and prevent from forming thrombus. It could also inhibit the constraction and slowing of blood flow of thin artery, the reducing of open capillaries and change of fluid condition caused by adrenalin and improve these phenomena. PT and KPTT could be increased obviously. Conclusion: LBC can significantly promote blood circulation by removing blood stasis, because of improving blood rheology and mesenteric microcirculatory disturbance and inhibit endogenous and exogenous coagulation system.