RESUMEN
Objective@#To study the effects of liraglutide on bone metabolism and Wnt pathway in type 2 diabetic osteoporosis rats.@*Methods@#SD rats were randomly divided into control group, model group and liraglutide group. The latter two groups were fed with high-fat and high-sugar diet and intraperitoneally injected with low-dose streptozotocin to establish type 2 diabetic model. Liraglutide group was subcutaneously injected with 0.6 mg/kg/d liraglutide for 8 weeks. Bone mineral density, calcium and phosphorus content, the expression of Wnt pathway molecule [Wnt3a, low density lipoprotein receptor-related protein 5 (LRP5) , β-catenin] and the contents of bone metabolism indicators [ALP, osteocalcin (OC) , osteoprotegerin (OPG) , receptor activator of nuclear factor-κ B ligand (RANKL) , tartrate-resistant acid phosphatase (TrACP) , cross-linked carboxy-terminal telopeptide of type I collagen (CTX-1) ] in serum were determined.@*Results@#The tibial bone mineral density[left (0.158±0.024) vs (0.232±0.041) g/cm2, right (0.152±0.027) vs (0.219±0.038) g/cm2, P<0.05) , the content of calcium and phosphorus [ (5.12±0.58) vs (5.93±0.74) mol/g, (2.93±0.41) vs (3.84±0.56) mol/g, P<0.05) , the expression of Wnt3a, LRP5, β-catenin in tibia [ (0.29±0.06) vs (0.78±0.13) , (0.30±0.05) vs (0.73±0.14) , (0.38±0.06) vs (1.01±0.18) , P<0.05], the content of ALP, OC and OPG in serum of model group were significantly lower than those of control group[ (40.27±7.52) vs (59.29±9.19) ng/ml, (252.45±42.95) vs (341.28±52.39) pg/ml, (0.40±0.06) vs (0.78±0.09) ng/ml, P<0.05) , and the contents of RANKL, TrACP and CTX-1 in serum were significantly higher than those of control group [ (17.79±2.84) vs (12.46±2.09) pg/ml, (56.45±7.79) vs (41.38±8.19) μmol/l, (19.26±3.14) vs (11.39±2.25) pg/ml, P<0.05]; the tibial bone mineral density, the content of calcium and phosphorus, the expression of Wnt3a, LRP5, β-catenin in tibia, the content of ALP, OC and OPG in serum of liraglutide group were significantly higher than those of control group, and the contents of RANKL, TrACP and CTX-1 in serum were significantly lower than those of control group.@*Conclusion@#Liraglutide can improve bone mineral density and bone metabolism in type 2 diabetic rats with osteoporosis, which may be related to activation of Wnt pathway.
RESUMEN
Objective To study the effects of liraglutide on bone metabolism and Wnt pathway in type 2 diabetic osteoporosis rats. Methods SD rats were randomly divided into control group, model group and liraglu-tide group. The latter two groups were fed with high-fat and high-sugar diet and intraperitoneally injected with low-dose streptozotocin to establish type 2 diabetic model. Liraglutide group was subcutaneously injected with 0.6 mg/kg/d liraglutide for 8 weeks. Bone mineral density, calcium and phosphorus content, the expression of Wnt path-way molecule [Wnt3a, low density lipoprotein receptor-related protein 5 (LRP5), β-catenin] and the contents of bone metabolism indicators [ALP, osteocalcin(OC), osteoprotegerin(OPG), receptor activator of nuclear factor-κ B ligand(RANKL), tartrate-resistant acid phosphatase(TrACP), cross-linked carboxy-terminal telopeptide of type I collagen (CTX-1)] in serum were determined. Results The tibial bone mineral density [left (0.158±0.024) vs (0.232±0.041) g/cm2, right(0.152±0.027) vs(0.219±0.038) g/cm2, P<0.05), the content of calcium and phospho-rus [(5.12±0.58) vs (5.93±0.74) mol/g, (2.93±0.41) vs (3.84±0.56) mol/g, P<0.05), the expression of Wnt3a, LRP5, β-catenin in tibia [(0.29±0.06) vs (0.78±0.13), (0.30±0.05) vs (0.73±0.14), (0.38±0.06) vs (1.01± 0.18), P<0.05], the content of ALP, OC and OPG in serum of model group were significantly lower than those of control group [(40.27±7.52) vs (59.29±9.19) ng/ml, (252.45±42.95) vs (341.28±52.39) pg/ml, (0.40±0.06) vs (0.78±0.09) ng/ml, P<0.05), and the contents of RANKL, TrACP and CTX-1 in serum were significantly higher than those of control group [(17.79±2.84) vs(12.46±2.09) pg/ml, (56.45±7.79) vs (41.38±8.19)μmol/l, (19.26± 3.14) vs (11.39±2.25) pg/ml, P<0.05]; the tibial bone mineral density, the content of calcium and phosphorus, the expression of Wnt3a, LRP5, β-catenin in tibia, the content of ALP, OC and OPG in serum of liraglutide group were significantly higher than those of control group, and the contents of RANKL, TrACP and CTX-1 in serum were significantly lower than those of control group. Conclusion Liraglutide can improve bone mineral density and bone metabolism in type 2 diabetic rats with osteoporosis, which may be related to activation of Wnt pathway.
RESUMEN
Aim To study the effects of harpagide on hippocampal neurons, mitochondrial function and caspase-independent apoptosis pathway after cerebral ischemia in mice. Methods The middle cerebral ar-tery occlusion (MCAO ) was employed to establish MCAO model. After that,the mice were given harp-agide (4,8,12 mg·kg - 1 )and edaravone (3. 2 mg ·kg - 1 )by tail vein injection after MCAO immediate-ly,and the model and control mice were given equal a-mounts of saline by the same way. After MCAO for 6 h,the apoptosis rate of hippocampal neuron and the mitochondrial membrane potential (MMP)of MCAO mice were detected by flow cytometry. We observed the clarity of inner and outer membrane of the hipp-ocampal neuronal mitochondrial,the integrity of the mitochondrial cristae,the changes of matrix electron density of mitochondria,and mitochondria swelling by transmission electron microscopy. Western blot was employed to determine the expression of apoptosis in-duced factor (AIF)and endonuclease G (Endo G)in mitochondrion and pro-caspase-3 in endochylema. qPCR was employed to determine the expression of AIF and Endo G. Results Compared with control group, the apoptosis rate of hippocampal neuron of MCAO mice significantly increased(P < 0. 01),the MMP of hippocampal neuron significantly decreased and the mi-tochondrial ultrastructure of cerebral ischemic area was severely damaged, loosely arranged and obviously swollen;the expression of AIF and Endo G in mito-chondria of cerebral tissue of MCAO mice significantly decreased,and the releases of AIF and Endo G signifi-cantly increased(P < 0. 01);the expressions of AIF, Endo G mRNA were evidently up-regulated (P <0. 01). Compared with model group,each dose of harpagide could significantly decrease the apoptosis rate of hippocampal neurons of mice brain (P < 0 . 05 ,P < 0. 01);MMP markedly increased in hippocampal nerve cells(P < 0. 01);the ultrastructure of neuronal mitochondria was obviously improved. Compared with model group,harpagide (8,12 mg·kg - 1 )could sig-nificantly increase the expression of AIF and Endo G protein in mitochondria of mouse brain,and the release of mitochondrial AIF and Endo G protein decreased(P< 0. 05,P < 0. 01);harpagide (4 mg·kg - 1 )could significantly increase the expression of Endo G protein in mitochondria of mouse brain,and the release of En-do G protein markedly decreased (P < 0. 05);harp-agide (8,12 mg·kg - 1 )could significantly decrease the expression of AIF and Endo G mRNA in hippocam-pus of mice(P < 0. 05,P < 0. 01). Conclusion The protective effect of harpagide on MCAO may be related to the protective effects on cerebral nerve cells,the ac-tivity of the mitochondria and the inhibition of caspase-independent apoptotic signaling pathways.
RESUMEN
To study the compensation standard of basic public health service a series of meetings were carried out,university faculty,scholars and public health workers as well as health administrators and policy makers actively joined the discussion.Based on the cost calculation of each items of public health service a preliminary proposal was developed.The proposal was disseminated for soliciting opinions widely and finalized.Finally the compensation standard of basic public health service both for urban and rural conununity health service centers and health stations were issued by Provincial Health Bureau.The compensation standard will provide support for implementation of basic public health policy in Fujian province.
RESUMEN
Fanconi anemia (FA) is an rare autosomal recessive inherited disease which manifests progressive marrow failure, congenital bone malformation, high risk to cancers and so on. Chromatin of FA cells display auto-instability and high hypersensitivity to interstrand DNA cross-links such as mitomycin C. As normally FA develop into acute myeloid leukemia easily, it has been regarded as pre-leukemia state. Till now 11 FA genes have been found and play a role in sustaining stability of gene groups through the same mechanism. As an active connecting protein, FANCF protein play an important part in correct FA complex formation. Which makes FANCD2 single ubiquitin. Ubiquitin FANCD2 induces chromatin and BRCA1 interact, and repair injured DNA. FA gene defect makes gene group instable and increases the risk of chromatin collapse, which finally leads to acute myeloid leukemia and myelodysplastic syndrome.