随着国际标准化心脏死亡器官捐献(donation after cardiac death, DCD)工作的广泛开展,DCD来源的供肾在临床的应用逐渐增多。DCD供肾移植术后并发症亦呈逐渐增加趋势,如移植肾缺血再灌注损伤、机会性病毒感染、排斥反应等,这就要求临床...随着国际标准化心脏死亡器官捐献(donation after cardiac death, DCD)工作的广泛开展,DCD来源的供肾在临床的应用逐渐增多。DCD供肾移植术后并发症亦呈逐渐增加趋势,如移植肾缺血再灌注损伤、机会性病毒感染、排斥反应等,这就要求临床医师评估供肾质量,除了临床评分及肉眼评估外,肾移植术中零点穿刺标本是评估移植肾功能、预测器官分配或远期存活的金标准[1]。展开更多
Objective To investigate effects of pirfenidone(PFD)on diabetic nephropathy model in db/db mice and to explore its possible mechanisms.Methods(1)Wildtype mice were as the normal control group,and db/db mice were divid...Objective To investigate effects of pirfenidone(PFD)on diabetic nephropathy model in db/db mice and to explore its possible mechanisms.Methods(1)Wildtype mice were as the normal control group,and db/db mice were divided into model group and PFD group,with 6 mice in each group.In the PFD group mice were administered continuously by 250 mg·kg^-1 ·d^-1 PFD for 18 weeks,and mice in the other two groups were administered by 0.5% sodium carboxymethyl cellulose.Blood glucose and 24 h urinary albumin were measured.The pathological changes of renal tissue were evaluated by PAS staining,PASM staining,Masson staining and Sirius red staining.The expression of collagen type Ⅳ in kidney tissues was detected by immunohistochemistry.(2)Mouse mesangial cells(SV40 MES-13 cells)were cultured as reaearch objects.They were divided into control group,hyperosmolar group,high glucose(HG)group,and 50,100,200,400,800,1600 mg/L PFD + HG group.BrdU cell proliferation test was used to evaluate cell proliferation rate.Cells were divided into control group,hyperosmolar group,HG group and PFD +HG group.The mRNA expressions of α-smooth muscle actin(α-SMA),collagen type Ⅰ,collagen type Ⅳ,transforming growth factor-β1(TGF-β1),interleukin(IL)-1β,IL-6 and monocyte chemotactic protein-1(MCP-1)were detected by real-time PCR.Results(1)Compared with normal control group,the model mice had higher weight,blood glucose and 24 h urinary albumin,accompanied with glomerular hypertrophy,mesangial area expansion,tubulointerstitial fibrosis and deposition of collagen type Ⅳ(all P<0.05).Compared with those in the model group,in the PFD group 24 h urinary albumin decreased,glomerular hypertrophy,mesangial area expansion and tubulointerstitial fibrosis alleviated,and the protein expression of collagen type Ⅳ was inhibited(all P<0.05).(2)Compared with those in HG group,MES-13 cell proliferation rates of 100,200,400,800,1600 mg/L PFD + HG groups decreased(all P<0.05),and the mRNA expressions of α-SMA,collagen type Ⅰ,collagen type Ⅳ,TGF-β1,IL-1β,IL-6 and MCP-1 reduced in 400 mg/L PFD + HG group(all P<0.05).Conclusion PFD can inhibit high glucoseinduced proliferation and activation of glomerular mesangial cells,decrease the expression of TGF-β1 and proinflammatory factors,as well as reduce the synthesis of collagen,which improve renal fibrosis of db/db mice.展开更多
文摘随着国际标准化心脏死亡器官捐献(donation after cardiac death, DCD)工作的广泛开展,DCD来源的供肾在临床的应用逐渐增多。DCD供肾移植术后并发症亦呈逐渐增加趋势,如移植肾缺血再灌注损伤、机会性病毒感染、排斥反应等,这就要求临床医师评估供肾质量,除了临床评分及肉眼评估外,肾移植术中零点穿刺标本是评估移植肾功能、预测器官分配或远期存活的金标准[1]。
文摘Objective To investigate effects of pirfenidone(PFD)on diabetic nephropathy model in db/db mice and to explore its possible mechanisms.Methods(1)Wildtype mice were as the normal control group,and db/db mice were divided into model group and PFD group,with 6 mice in each group.In the PFD group mice were administered continuously by 250 mg·kg^-1 ·d^-1 PFD for 18 weeks,and mice in the other two groups were administered by 0.5% sodium carboxymethyl cellulose.Blood glucose and 24 h urinary albumin were measured.The pathological changes of renal tissue were evaluated by PAS staining,PASM staining,Masson staining and Sirius red staining.The expression of collagen type Ⅳ in kidney tissues was detected by immunohistochemistry.(2)Mouse mesangial cells(SV40 MES-13 cells)were cultured as reaearch objects.They were divided into control group,hyperosmolar group,high glucose(HG)group,and 50,100,200,400,800,1600 mg/L PFD + HG group.BrdU cell proliferation test was used to evaluate cell proliferation rate.Cells were divided into control group,hyperosmolar group,HG group and PFD +HG group.The mRNA expressions of α-smooth muscle actin(α-SMA),collagen type Ⅰ,collagen type Ⅳ,transforming growth factor-β1(TGF-β1),interleukin(IL)-1β,IL-6 and monocyte chemotactic protein-1(MCP-1)were detected by real-time PCR.Results(1)Compared with normal control group,the model mice had higher weight,blood glucose and 24 h urinary albumin,accompanied with glomerular hypertrophy,mesangial area expansion,tubulointerstitial fibrosis and deposition of collagen type Ⅳ(all P<0.05).Compared with those in the model group,in the PFD group 24 h urinary albumin decreased,glomerular hypertrophy,mesangial area expansion and tubulointerstitial fibrosis alleviated,and the protein expression of collagen type Ⅳ was inhibited(all P<0.05).(2)Compared with those in HG group,MES-13 cell proliferation rates of 100,200,400,800,1600 mg/L PFD + HG groups decreased(all P<0.05),and the mRNA expressions of α-SMA,collagen type Ⅰ,collagen type Ⅳ,TGF-β1,IL-1β,IL-6 and MCP-1 reduced in 400 mg/L PFD + HG group(all P<0.05).Conclusion PFD can inhibit high glucoseinduced proliferation and activation of glomerular mesangial cells,decrease the expression of TGF-β1 and proinflammatory factors,as well as reduce the synthesis of collagen,which improve renal fibrosis of db/db mice.
