肾康注射液对腹膜纤维化小鼠E-cadherin和α-SMA动态表达的影响

摘要

Objective:To investigate the effects of Shenkang injection (SKI)on peritoneal form、function and the expression of E-cadherin、α-SMA in mice model of peritoneal dialysis and its potential mechanism of prevention peritoneal fibrosis.Methods:Mice model of peritoneal fibrosis was induced by high glucose dialysate (4.25％,Baxter).The mice were randomly divided into five groups:control group,4.25％ PDS model group,4.25％ PDS + SKI low,middle and high dose groups.Control mice (n =8):received no treatment;model group (n =24):mice were treated with daily intraperitoneal injection of 4.25％ peritoneal dialysate (100 mL· kg-1 body weight);4.25 ％ PDS + SKI low (n =24),middle (n =24) and high (n =24) dose groups:mice were treated with daily intraperitoneal injection of 4.25％ peritoneal dialysate plus 4.5 mL· kg-1 SKI,9 mL· kg-1 SKI,18 mL· kg-1 SKI.At 2,4,6W of study,8 mice of 4.25％ PDS model group and 4.25％ PDS + SKI low,middle,high groups were randomly drew out and did experiment.Results:Normal peritoneums were covered by a layer flat mesothelial cell.Comparing with the mice in normal group,the peritoneums of the 4.25％ PDS model group were significantly thicker than the control group.Magnanimous collagen fibrils deposition,Ultrafiltration volume and endotoxin clearance rate were dramatic decline.Furthermore,were gradually deteriorated over time.Comparing with the mice in 4.25％ PDS modle group,the Peritoneal thickness of the 4.25％ PDS + SKI groups(include low,middle and high dose) had varying degrees of ease.Their ultrafiltration volume and endotoxin clearance rate were increased.The expression level of α-SMA in 4.25％ PDSmodel group was significantly higher than that in control group.Compared with the 4.25％ PDS model group,the 4.25％ PDS + SKI groups were significantly lower.Compared with the control group,the expression level of E-cadherin in 4.25％ PDS model group was decreased,the expression level of E-cadherin in 4.25％ PDS + SKI groups were increased than the model group.The changes of 4.25％ PDS + SKI the middle、high dose groups were the most significant for 4 weeks and 6 weeks.Conclusion:Shenkang injection may delay the progress of peritoneal fibrosis by inhibiting the transdifferentiation of peritoneal mesothelial cells,delay the progress of peritoneal fibrosis,and with the increase of the dosage and duration of treatment,the curative effect is more significant.%目的:探讨中药肾康注射液(Shenkang injection,SKI)对腹膜透析(peritoneal dialysis,PD)诱导的小鼠腹膜纤维化模型的腹膜形态和功能,以及对E-钙粘素(E-cadherin)、α-平滑肌肌动蛋白(α-SMA)动态表达的影响,初步探讨SKI对腹膜纤维化的防治作用及可能机制.方法:采用4.25％含葡萄糖腹膜透析液诱导腹膜纤维化模型.将小鼠随机分成5组:对照组、模型组、SKI低剂量组、SKI中剂量组、SKI高剂量组,实验周期为6周,分别于实验周期2,4和6周动态测定各组腹膜功能,取壁层腹膜组织进行HE及Masson染色,观察腹膜形态学动态改变,Western Blot方法检测脏层腹膜E-cadherin,α-SMA的动态表达情况.结果:模型组腹膜较对照组明显增厚(P＜0.05),胶原纤维大量沉积,超滤量、毒素清除率明显下降(P＜0.05),且随着时间的延长而逐渐恶化;SKI治疗组腹膜病变较模型组均有不同程度减轻,毒素清除率及超滤量增多(P＜0.05);模型组腹膜α-SMA的表达水平明显高于对照组(P＜0.05),SKI治疗组较模型组显著降低(P＜0.05),模型组膜E-cadherin的表达水平下降,SKI治疗组较模型组均显著升高(P＜0.05),以实验4和6周中、高剂量组最为显著.结论:SKI可能通过抑制腹膜间皮细胞的转分化,促进E-cadherin、抑制α-SMA的表达,延缓腹膜纤维化的进展,且随着用药剂量增加及用药时间的延长,疗效越为显著,呈动态变化.