己酮可可碱对腹膜纤维化形成的干预作用

Effects of Pentoxifylline on Peritoneal Fibrosis

目的探讨己酮可可碱(PTX)对SD大鼠腹膜纤维化病变的影响和可能的机制。方法将大鼠随机分成3组:对照组,模型组和治疗组(PTX组)。用4.25%含糖腹膜透析液+脂多糖腹腔注射制作腹膜纤维化模型,即模型组;PTX组同时每日给予PTX6mg/kg腹腔注射。5周后行2h腹膜平衡试验测定腹膜功能,留取血液及腹膜透析液用ELISA法测定血管内皮生长因子(VEGF)浓度,并留取壁层腹膜组织做苏木精-伊红、Masson染色,RT-PCR检测肠系膜组织VEGFmRNA表达水平。结果①模型组及PTX组的壁层腹膜较对照组增厚,而PTX组较模型组明显减轻;②模型组及PTX组大鼠超滤量及2h透析液葡萄糖浓度/0h透析液葡萄糖浓度(D2/D0)比值均较对照组减少(均P<0.05),其中模型组较PTX组明显减少;与对照组比较,模型组及PTX组大鼠透析液尿素浓度/血浆尿素浓度(Durea/Purea)比值有明显增加(均P<0.05),其中模型组较PTX组增加明显;③PTX组腹透液及血清中VEGF浓度,肠系膜组织VEGFmRNA表达较模型组明显下降(均P<0.05)。结论己酮可可碱能有效地预防腹膜纤维化,其机制可能与调节VEGF的表达有关。

Objective To investigate the effect and possible mechanism of pentoxifylline in treating peritoneal fibrosis of SD rats. Methods All rats were randomly divided into three groups： control group, model group and pentoxifylline-treated group. The rat model of peritoneal fibrosis was induced by high glucose peritoneal dialysis fluid （4.25%, Baxter） and lipopolysaccharide （LPS） （model group）. In pentoxifylline-treated group, pentoxifylline （6 mg/kg） was intraperitoneally injected daily. Five weeks later the function of peritoneum was evaluated by a 2-h peritoneum equilibrium test （PET） and vascular endothelial growth factor （VEGF） in blood and dialysate was detected by ELISA method. The peritoneum was stained with HE and Masson method. The expression of VEGF mRNA in mesentery was assayed by RT-PCR method. Results （1） The parietal peritoneum in pentoxifylline-treated group was significantly thinner than in model group; （2） Glucose reabsorption （D2/D0） and net ultrafitration （UF） volume in model group and pentoxifylline-treated groups were significantly reduced as compared with control group, and those in model group were also obviously less than in pentoxifylline-treated group; Dialysate-to-plasma Urea ratio （Durea/Purea） in model group and pentoxifylline-treated groups was significantly higher than in control group, and that in model group was obviously higher than in pentoxifylline-treated group; （3） The concentration of VEGF was decreased obviously in blood and dialysate and VEGF mRNA expression level in mesentery was down-regulated in pentoxifylline-treated group. Conclusion Pentoxifylline is beneficial to the prevention and treatment of peritoneal fibrosis by regulating the expression of VEGF.