ABSTRACT
Sarcopenia and osteoporosis are two common diseases with adverse effects on the health of the elderly and share many characteristics.As target organs of the two diseases,muscles and bones are closely connected,not only in anatomy and physiology,but also in pathophysiological processes.Initially,mechanical stimulation was conducted to explain the relationship between muscle and bone at the macroscopic level.Currently,research is increasingly focused at the cellular and molecular levels.Both muscle and bone tissues can secrete a number of growth factors,cytokines,polypeptides,and so on.Myokines include fibroblast growth factor-2 (FGF-2),myostatin,irisin,insulinlike growth factor-1 (IGF-1),interleukins,musclin,among others.Osteokines comprise osteocalcin,fibroblast growth factor-23,IGF-1,vascular endothelial growth factor,etc.In this review,we summarize the roles of myokines and osteokines in muscle-bone interactions.
ABSTRACT
<p><b>OBJECTIVE</b>To explore the effects of angiotensin-(1-7) on the learning and memory abilities and the expressions of glial fibrillary acidic protein (GFAP) and glial cell line-derived neurotrophic factor (GDNF) in the hippocampus of diabetic rats.</p><p><b>METHODS</b>Forty male SD rats were randomly assigned into 4 groups, namely the control group, diabetic group, Ang(1-7)-treated diabetic group (DM1 group), and Ang-(1-7)- and Mas receptor antagonist A779-treated diabetic group (DM2 group). Diabetic rat models were established by a single intraperitoneal injection of streptozotocin (60 mg/kg). The cognitive function of the rats was assessed with Morris water maze (MWM) test. The expressions of GDNF in the hippocampus were examined by RT-PCR and Western blot. Nissl staining was performed to evaluate the morphological changes in rat hippocampus. The expressions of glial fibrillary acidic protein (GFAP, a key indicator of astrocytic reactivity) and caspase-3 were measured by immunohistochemistry.</p><p><b>RESULTS</b>Compared with the control group, the diabetic rats exhibited significantly impaired learning and memory abilities (P<0.05) with lowered expression of GDNF and increased caspase-3 expression in the hippocampus (P<0.05) and significant hippocampal neuronal and astrocyte injuries (P<0.05). Treatment with Ang(1-7) obviously improved the learning and memory abilities of the diabetic rats (P<0.05), increased GDNF and GFAP expressions (P<0.05), lowered caspase-3 expression (P<0.05), and increased the number of surviving neurons in the hippocampus (P<0.05). Such effects of Ang(1-7) effect was blocked by treatment with A779 of the diabetic rats.</p><p><b>CONCLUSION</b>Ang(1-7) can alleviate cognitive dysfunction in diabetic rats possibly by up-regulating the expressions of GFAP and GDNF and promoting neuron survival in the hippocampus.</p>
Subject(s)
Animals , Male , Rats , Angiotensin I , Pharmacology , Astrocytes , Caspase 3 , Metabolism , Cognition , Cognition Disorders , Diabetes Mellitus, Experimental , Glial Cell Line-Derived Neurotrophic Factor , Metabolism , Glial Fibrillary Acidic Protein , Metabolism , Hippocampus , Cell Biology , Metabolism , Memory , Neurons , Peptide Fragments , Pharmacology , Rats, Sprague-Dawley , StreptozocinABSTRACT
Objective To explore how does chymase affect diabetic cardiomyopathy by investigating the gene expression of chymase and the relationship between the gene expression of chymase and the angiotensin Ⅱ in the cardiomyopathy of streptozotocin-induced diabetic hamasters. Methods Diabetic hamsters were induced by intraperitoneal injection of STZ 40 mg/kg once a day for 3 days. After stabilization of diabetic state for 18 weeks, the myocardial ultrastructure was observed with electron microscope and pathologic changes were observed by light microscopy. Immunohistochemistry was used to measure the level of expression of type Ⅰ and type Ⅲ collagen in diabetic and normal hamster hearts. Level of blood glucose, lipoprotein was determined using biocehemical methods. Apoptosis of cardiomyocyte was measured using TUNEL methods. Radioimmunuoassay method was used to determine the level of angiotensin Ⅱ. RT-PCR was used to determine chymase gene expression (corrected by?-actin). ResultsComparing with the control group, levels of serum glucose, TG, TC, LDL in DM group were much higher. Concentrations of collagen Ⅰ, Ⅲ and angiotensin Ⅱ [(95.8?16.0)?g/kg tissue vs (51.1?20.8)?g/kg tissue] in myocardial tissue in DM group were much higher than those in control group. RT-PCR result showed: Comparing with the control group, the mRNA expression of chymase in DM group was promoted significantly (0.810?0.026 vs 0.490?0.087). Conclusion In diabetic hamsters, the gene expression of chymase were much higher than thatin the control group, accompanying higher level of Angiotensin Ⅱ, higher levels of expression of collagen Ⅰ and Ⅲ. This result suggests that chymase plays an important role in the diabetic cardiomyopathy by promoting the activity of chymase.