BACKGROUND:Aerobic exercise can suppress liver fibrosis in diabetic mice.However,the specific mechanism is yet to be elucidated.OBJECTIVE:To investigate the protective effect and mechanism of aerobic exercise on liver fibrosis in db/db mice via the transforming growth factor-β/Smad signaling pathway.METHODS:8-week-old male db/db mice and age-matched m/m mice were randomly divided into m/m control group,m/m+exercise group,db/db control group,and db/db+exercise group,with 10 mice in each group.Mice in the exercise group were subjected to a 12-week aerobic exercise.After the exercise,fasting blood glucose levels were measured in mice,and glucose tolerance and insulin tolerance tests were conducted.Mouse liver was extracted to calculate liver index and mouse eyeballs were taken to collect blood sample and detect biochemical indicators.Masson,oil red O and Hematoxylin-eosin staining were used to detect and analyze the pathological changes in mouse liver tissues.Immunohistochemistry was used to determine the protein expression levels of transforming growth factor-β1 and p-Smad3.Western blot analysis was applied to determine the protein expression levels of transforming growth factor-β1,Smad3,p-Smad3,α-smooth muscle actin,type I collagen and type III collagen.RESULTS AND CONCLUSION:Compared with the m/m group and m/m+exercise group,body mass,liver mass,liver index,fasting blood glucose,triglycerides,total cholesterol,low-density lipoprotein and creatine kinase levels were significantly increased(P<0.01),but the high-density lipoprotein level significantly decreased(P<0.01)in the db/db group;the protein expressions of transforming growth factor-β1,p-Smad3,α-smooth muscle actin,type I collagen and type III collagen significantly increased(P<0.01)in the db/db group;the area under curve of glucose and insulin tolerance tests significantly increased(P<0.01)in the db/db group;and pathological staining of the liver in the db/db group showed extensive infiltration of inflammatory cells,increased lipid droplets,and significant fibrosis.In the db/db+exercise group,aerobic exercise could significantly reduce body mass,liver mass,liver index,fasting blood glucose,triglycerides,total cholesterol,low-density lipoprotein and creatine kinase levels(P<0.05 or P<0.01),and increase high-density lipoprotein level(P<0.05).Similarly,a marked decrease was observed in the protein expression levels of transforming growth factor-β1,p-Smad3,α-smooth muscle actin,type I collagen and type III collagen(P<0.05 or P<0.01)in the db/db+exercise group.In addition,the area under the curve of glucose tolerance and insulin tolerance tests significantly decreased(P<0.01,P<0.05),and pathological changes in liver tissues were significantly improved.In conclusion,aerobic exercise can attenuate liver fibrosis in diabetic mice,which may be related to the regulation of the transforming growth factor-β1/Smad signaling pathway.

[摘 要] 目的：探究地塞米松联合阿比特龙对去势抵抗性前列腺癌（CRPC）患者尿流动力学、外周血循环肿瘤细胞雄激素受体剪切变异体7（AR-V7）、人同源盒基因B13（HoxB13）水平及生存预后的影响。方法：回顾性选取本院收治的114例CRPC患者病历资料，根据治疗方案分为对照组（予以0.5 mg地塞米松治疗，n = 51）和观察组（予以0.5 mg地塞米松联合1 000 mg阿比特龙治疗，n = 63）。比较两组疗效、尿动力学、外周血循环肿瘤细胞AR-V7、HoxB13水平以及生存预后。结果：观察组63例，对照组51例。治疗8周后，观察组疾病控制率与客观缓解率（分别为42.86%与96.83%）均显著高于对照组（分别为23.53%与86.27%）（P < 0.05）。观察组的最大尿流率[（14.58 ± 1.02）mL/s vs （11.18 ± 1.16）mL/s）]、平均尿流率[（12.92 ± 1.21）mL/s vs （9.83 ± 0.59）mL/s）]均显著高于对照组，而剩余尿量[（24.12 ± 1.96）mL vs （28.03 ± 1.68）mL）]显著低于对照组（均P < 0.05）。观察组与对照组的AR-V7 mRNA表达水平相近[（1.78 ± 0.32） vs （1.68 ± 0.46）]，差异无统计学意义（P > 0.05）；但观察组的HoxB13 mRNA表达水平显著低于对照组[（1.21 ± 0.27） vs （1.57 ± 0.37），P < 0.05]。观察组的中位无进展生存期[6.22个月（95%CI：5.63~6.63）]显著长于对照组[3.66个月（95%CI：3.01~3.74）]（P < 0.05）；观察组的3年总生存率为12.70%，显著高于对照组的0.00%（P < 0.05）。结论：地塞米松联合阿比特龙治疗CRPC患者具有显著疗效，能明显改善患者尿流动力，下调外周血循环肿瘤细胞中HoxB13的表达，未显著影响AR-V7的表达，还能延长患者PFS，提高3年总生存率。

BACKGROUND:Aerobic exercise can suppress liver fibrosis in diabetic mice.However,the specific mechanism is yet to be elucidated.OBJECTIVE:To investigate the protective effect and mechanism of aerobic exercise on liver fibrosis in db/db mice via the transforming growth factor-β/Smad signaling pathway.METHODS:8-week-old male db/db mice and age-matched m/m mice were randomly divided into m/m control group,m/m+exercise group,db/db control group,and db/db+exercise group,with 10 mice in each group.Mice in the exercise group were subjected to a 12-week aerobic exercise.After the exercise,fasting blood glucose levels were measured in mice,and glucose tolerance and insulin tolerance tests were conducted.Mouse liver was extracted to calculate liver index and mouse eyeballs were taken to collect blood sample and detect biochemical indicators.Masson,oil red O and Hematoxylin-eosin staining were used to detect and analyze the pathological changes in mouse liver tissues.Immunohistochemistry was used to determine the protein expression levels of transforming growth factor-β1 and p-Smad3.Western blot analysis was applied to determine the protein expression levels of transforming growth factor-β1,Smad3,p-Smad3,α-smooth muscle actin,type I collagen and type III collagen.RESULTS AND CONCLUSION:Compared with the m/m group and m/m+exercise group,body mass,liver mass,liver index,fasting blood glucose,triglycerides,total cholesterol,low-density lipoprotein and creatine kinase levels were significantly increased(P<0.01),but the high-density lipoprotein level significantly decreased(P<0.01)in the db/db group;the protein expressions of transforming growth factor-β1,p-Smad3,α-smooth muscle actin,type I collagen and type III collagen significantly increased(P<0.01)in the db/db group;the area under curve of glucose and insulin tolerance tests significantly increased(P<0.01)in the db/db group;and pathological staining of the liver in the db/db group showed extensive infiltration of inflammatory cells,increased lipid droplets,and significant fibrosis.In the db/db+exercise group,aerobic exercise could significantly reduce body mass,liver mass,liver index,fasting blood glucose,triglycerides,total cholesterol,low-density lipoprotein and creatine kinase levels(P<0.05 or P<0.01),and increase high-density lipoprotein level(P<0.05).Similarly,a marked decrease was observed in the protein expression levels of transforming growth factor-β1,p-Smad3,α-smooth muscle actin,type I collagen and type III collagen(P<0.05 or P<0.01)in the db/db+exercise group.In addition,the area under the curve of glucose tolerance and insulin tolerance tests significantly decreased(P<0.01,P<0.05),and pathological changes in liver tissues were significantly improved.In conclusion,aerobic exercise can attenuate liver fibrosis in diabetic mice,which may be related to the regulation of the transforming growth factor-β1/Smad signaling pathway.