腹膜透析液中添加丹参酮对大鼠氧化应激状态的影响

Accumulation of advanced glycation end products in the peritonium and changes of oxidative stress in continuous ambulatory peritoneal dialysis patients

目的探讨在腹膜透析液中添加丹参酮注射液对大鼠腹膜局部保护作用及全身氧化应激状态的影响。方法40只SD雄性大鼠（180－200g）随机分为A、B、C、D四组，每组10只。A组为正常对照组。每日用生理盐水腹腔注射20ml；B组为腹膜透析组，每日用4．25％的腹膜透析液腹腔注射20ml；C、D组为丹参酮低、高浓度组，每日分别用含丹参酮浓度为50mg／L和100mg／L的4．25％腹膜透析液，腹腔注射20ml。于实验第30天在腹腔注射用药2小时后杀检动物。取腹主动脉血2m1和透出液1ml。测定并比较四组大鼠其透出液及血清氧化应激指标：谷胱甘肽（GSH）、丙二醛（MDA）含量及总超氧化物岐化酶（T．SOD）活性。同时取壁层腹膜组织行光镜检查。结果与A组比较，B组大鼠透出液及血清GSH、T—SOD明显降低（P〈0．05）、MDA明显升高（P〈0．05）。C、D组大鼠血清及透出液GSH、T-SOD均较B组显著升高（P〈0．05），透出液MDA在用药后显著降低（P〈0．05），D组表现最为显著。即丹参酮治疗组大鼠血清及透出液氧化应激指标与透析液中加入丹参酮浓度呈负相关（P〈0．05）。壁层腹膜HE染色显示，与A组比较。30天时各组壁层腹膜组织均明显增厚，有大量胶原沉积，其中B组最为显著。结论高浓度葡萄糖透析液可出现透析大鼠腹腔液及全身高氧化应激状态，可导致透析大鼠腹膜纤维化。在透析液中添加丹参酮对体外腹膜透析液中糖基化终产物形成和腹膜纤维化有明显抑制作用，且丹参酮IIA的这种抑制作用呈现剂量依赖性。提示丹参酮IIA具有潜在延缓腹膜透析伴发腹膜纤维化发生的作用。

Objective To investigate local protective effects and the impact on oxidative stress of Tanshlnone on peritoneal dialysis fluid in peritoneal dialysis in rat. Methods 40 male Sprague-Dawley rats were randomized into 4 groups IGroup A, B, C and D）. 20ml physiological saline was injected into peritoneal cavity once a day for 30 consecutive days for rats in group A, as well as 20ml 4. 25% peritoneal dialysis solution （PDS） for rats in group B, and 20ml 4.25% PDS containing Tanshinone 50mg/L and 100mg/L for rats in group C and group D, respectively. Then the rats were sacrificed 30 days after injection. The concentration in serum and effluent of oxidative stress markers such as glutathione C GSH）, total-superoxide dismutase（T-SOD）, malondialdehyde （MDA）, albumin concentration in serum were measured. AGEs in serum and effluent were detected. Results The serum and effluent GSH and T-SOb in rat group B were significantly lower （P〈0.05） and the concentration in serum and effluent of MDA, AGEs were significantly higher （P〈0. 05 ） than that of Group A. There was negative correlation between GSH, T-SOD and of AGEs （P〈0. 05） and positive correlation between MDA and AGEs. After using high Tanshinone in peritoneal dialysis fluid, serum and effluent of GSH and T-SOD was significantly higher than that before treatment （P〈0. 05 ） and the concentration in effluent of MDA was significantly lower than that be/ore treatment （P〈0. 05）. There is a negative correlation between serum and effluent of AGEs of Tanshinone used in rats and the concentration of Tanshinone （P〈0. 05）. Conclusion The concentration in serum and effluent of AGEs were increased significantly, and AGEs could have strengthened oxidative stress in the abdominal cavity through high concentrations of glucose dialysis solution. Tanshinone can palliate oxidative stress in PD rats.The higher the concentration of Tanshinone, the better the effects.