Objective To investigate the effects of SAC/VAL on myocardial fibrosis and miR-21 expression in rats induced by AAC.Methods A total of 72 SPF SD male rats were randomly di-vided into sham operation group,AAC group,low-and high-dose SAC/VAL groups,high-dose SAC/VAL+agomiR-NC group,and high-dose SAC/VAL+miR-21 agomiR group,with 12 rats in each group.Echocardiography was used to test cardiac function.HE staining and Masson staining were applied to observe the pathological changes in myocardial tissues and myocardial tissue fi-brosis,respectively.Immunohistochemical assay was employed to detect the expression of α-SMA and COL-l in myocardial tissue.Real-time fluorescence quantitative polymerase chain reaction was conducted to detect miR-21 level.Results Compared with the sham operation group,the AAC group had thicker and broken myocardial fibers in disordered arrangement,hypertrophic myocar-dial cells with condensed and deeply stained nuclei,and extensive infiltration of inflammatory cells,and obvious myocardial fibrosis,increased LVEDD and LVESD values,and up-regulated miR-21,α-SMA and COL-1 expression,but decreased LVEF and LVFS levels(P＜0.05).Low-and high-dose SAC/VAL treatment resulted in well-arranged less broken myocardial fibers in uniform distribution,relatively normal myocardial cells,less inflammatory cell infiltration,and reduced severity of myocardial fibers,lower LVEDD and LVESD values,decreased miR-21,α-SMA and COL-1 levels,but increased LVEF and LVFS levels when compared to the AAC group(P＜0.05).When compared to the high dose SAC/VAL+agomiR NC group,the high-dose SAC/VAL+miR-21 agomiR group had disorderly-arranged myocardial fiber with thickening and breakage,aberrant myocardial cells,obvious infiltration of inflammatory cells,and intensified my-ocardial fibrosis,higher LVEDD and LVESD values and miR-21,α-SMA and COL-1 expression levels,and lower LVEF and LVFS levels[7.11±0.45 mm vs 6.05±0.38 mm,P＜0.05;5.58±0.35 mm vs 4.01±0.28 mm,P＜0.05;2.57±0.14 vs 0.98±0.10,P＜0.05;0.62±0.06 A vs 0.41±0.04 A,P＜0.05;0.79±0.08 A vs 0.53±0.05 A,P＜0.05;(58.26±2.61)％vs(80.24±2.87)％,P＜0.05;(24.52±1.03)％vs(33.72±1.25)％,P＜0.05].Conclusion SAC/VAL inhibits AAC-induced myocardial fibrosis in rats,which is related to its regulation of miR-21 expression.

Objective To investigate the effects of SAC/VAL on myocardial fibrosis and miR-21 expression in rats induced by AAC.Methods A total of 72 SPF SD male rats were randomly di-vided into sham operation group,AAC group,low-and high-dose SAC/VAL groups,high-dose SAC/VAL+agomiR-NC group,and high-dose SAC/VAL+miR-21 agomiR group,with 12 rats in each group.Echocardiography was used to test cardiac function.HE staining and Masson staining were applied to observe the pathological changes in myocardial tissues and myocardial tissue fi-brosis,respectively.Immunohistochemical assay was employed to detect the expression of α-SMA and COL-l in myocardial tissue.Real-time fluorescence quantitative polymerase chain reaction was conducted to detect miR-21 level.Results Compared with the sham operation group,the AAC group had thicker and broken myocardial fibers in disordered arrangement,hypertrophic myocar-dial cells with condensed and deeply stained nuclei,and extensive infiltration of inflammatory cells,and obvious myocardial fibrosis,increased LVEDD and LVESD values,and up-regulated miR-21,α-SMA and COL-1 expression,but decreased LVEF and LVFS levels(P＜0.05).Low-and high-dose SAC/VAL treatment resulted in well-arranged less broken myocardial fibers in uniform distribution,relatively normal myocardial cells,less inflammatory cell infiltration,and reduced severity of myocardial fibers,lower LVEDD and LVESD values,decreased miR-21,α-SMA and COL-1 levels,but increased LVEF and LVFS levels when compared to the AAC group(P＜0.05).When compared to the high dose SAC/VAL+agomiR NC group,the high-dose SAC/VAL+miR-21 agomiR group had disorderly-arranged myocardial fiber with thickening and breakage,aberrant myocardial cells,obvious infiltration of inflammatory cells,and intensified my-ocardial fibrosis,higher LVEDD and LVESD values and miR-21,α-SMA and COL-1 expression levels,and lower LVEF and LVFS levels[7.11±0.45 mm vs 6.05±0.38 mm,P＜0.05;5.58±0.35 mm vs 4.01±0.28 mm,P＜0.05;2.57±0.14 vs 0.98±0.10,P＜0.05;0.62±0.06 A vs 0.41±0.04 A,P＜0.05;0.79±0.08 A vs 0.53±0.05 A,P＜0.05;(58.26±2.61)％vs(80.24±2.87)％,P＜0.05;(24.52±1.03)％vs(33.72±1.25)％,P＜0.05].Conclusion SAC/VAL inhibits AAC-induced myocardial fibrosis in rats,which is related to its regulation of miR-21 expression.

Objective To prepare a new bone-targeted drug of epirubicin-oxidized dextran-alendronate compound,and explore the effect of compound on osteosarcoma cells.Methods (1) Based on Schiff's base theory,we synthesized the compound.(2) We investigated physicochemical character with ultraviolet (UV),infrared (IR),and 1H-nuclear magnetic resonance (1H-NMR),molecular weight and aldehyde group content in oxidized dextran,alendronate content in oxidized dextran-alendronate compound,epirubicin drug loading capacity in the compound,and rate of charge for three matters,and affinity to bone in vitro though Hydroxyapatite (HA) absorbing test.(3) We investigated the compound's cytotoxicity effect through methyl thiazolyl tetrazolium (MTT) test,apoptosis influence through flow cytometry (FCM).Results (1) There were typical physicochemical characters.(2) Oxidized dextran molecular weight (MW) was 4 251 ± 68,number of average molecular weight (MN) was 2 551 ± 42,and molecular weight distribution width was 1.78.Aldehyde group content of oxidized dextran was (10.41 ± 0.2)mmol/mg,epirubicin drug loading capacity was (5.28 ± 0.23) ％,rate of charge was 5,and 2 ～ 3 between aldehyde group content in oxidized dextran and alendronate (ALN).(3) In the MTT test,epirubicin (EPI)-Dex-ALN,EPI,ALN obviously restrained osteosarcoma cell proliferation,the minimum concentration(μg/ml) was 1,1,and 40; IC50 (μg/ml) of EPI-Dex-ALN,EPI,ALN was 0.142,0.505,0.219; 0.251,0.739,and 0.518; 45.21,27.97,and 18.96 after 24 h,48 h,72 h; in FCM (flow cytometry),apoptosis and necrosis rate of EPI-Dex-ALN,ALN,and Dex was 80.13 ±4.05,97.01 ±2.58,31.53 ±6.9,and 14.01 ±2.51.Conclusions We successfully synthesized a new bone-targeted drug delivery system,which showed better bone affinity in vivo,and kept biological activity with powerful targeted function.