鳖甲煎丸对腹膜透析相关腹膜纤维化的影响及机制探讨

目的探讨鳖甲煎丸对腹膜透析(PD)小鼠腹膜纤维化的抑制作用及可能机制。方法采用ICR小鼠4.25%腹透液2.0 mL每日腹腔注射一次,并于第3、5、7天联合脂多糖0.8 mg/kg腹腔注射造模;鳖甲煎丸1.2 g/kg每日灌胃一次,干预6周后,测腹透超滤量,HE染色和Masson染色观察壁层腹膜形态改变及腹膜厚度;Western blot检测脏层腹膜组织N-cadherin、ZO-1的蛋白表达水平,及pAkt、总Akt的蛋白表达水平。结果腹膜透析(PD)组、鳖甲煎丸(BJJW)组与对照(Control)组比较,超滤量均显著下降(P0.05);壁层腹膜均显著增厚(P0.01)。脏层腹膜ZO-1蛋白表达降低,N-cadherin蛋白表达升高,pAkt也明显升高(均P0.01)。BJJW组与PD组比较,超滤量明显改善(P0.05),壁层腹膜厚度降低(P0.01);脏层腹膜ZO-1蛋白表达增加,N-cadherin蛋白表达下降,pAkt也明显下降(均P0.01)。结论鳖甲煎丸抑制腹膜纤维化,PI3K/Akt信号调节腹膜间皮细胞上皮-间质细胞转分化(EMT)是其机制之一。

Effect of Biejiajian pill on peritoneal dialysis related peritoneal fibrosis and its mechanism

Objective To investigate the inhibitory effect of Biejiajian pill on peritoneal fibrosis in peritoneal dialysis(PD) mice and its possible mechanism.Methods ICR mice were injected intraperitoneally with 4.25% peritoneal dialysis solution 2.0 mL once a day,combined with lipopolysaccharide 0.8 mg/kg on the 3rd,5th and 7th day to build model.Biejiajian pill 1.2 g/kg were administrated daily by gavage.After 6 weeks of intervention,the volume of peritoneal ultrafiltration was measured,HE staining and Masson staining were used to observe the changes in peritoneal morphology and peritoneal thickness of the parietal peritoneum.Western blot was used to detect the expression levels of N-cadherin and ZO-1,pAkt and total Akt in visceral peritoneal tissue.Results Compared with that of the control group,the volume of peritoneal ultrafiltration in the peritoneal dialysis(PD) group and Biejiajian pill(BJJW) group was significantly lower(P<0.05),and the parietal peritoneum in PD group and BJJW group was significantly thickened(P<0.01).Visceral peritoneal ZO-1 protein expression was reduced,N-cadherin protein expression was increased,and pAkt was also significantly increased(P<0.01).Compared with that of the PD group,the volume of peritoneal ultrafiltration in BJJW group was significantly improved,and the peritoneal thickness of the parietal peritoneum decreased(P<0.05).The visceral peritoneal ZO-1 protein expression increased,N-cadherin protein expression decreased,and pAkt also significantly decreased (all P<0.01).Conclusion Biejiajian pill inhibits peritoneal fibrosis,and the regulation of epithelial to mesenchymal transition(EMT) of peritoneal mesothelial cells from PI3K/Akt signal is one of its mechanisms.