化痰祛瘀法对腹膜纤维化大鼠TGF-β/Smad信号通路的影响

【目的】探讨化痰祛瘀法对腹膜纤维化大鼠转化生长因子-β(TGF-β)/Smad信号通路的影响。【方法】选用健康SD雄性大鼠60只,随机分为5组,每组12只,分别为:空白组、模型组、西药组、中药高剂量组、中药低剂量组。复制大鼠腹膜纤维化模型后,即实验第5周开始,中药高、低剂量组分别给予化痰祛瘀中药50、25 mg.kg-1.d-1,西药组给予贝那普利5 mg.kg-1.d-1,模型组及空白组灌服注射用水,每天1次,共4周。实验第8周结束后留取腹膜组织,采用免疫组化法测定脏层腹膜p-Smad2/3、Smad7和TGF-β1表达情况。【结果】中药高剂量组、中药低剂量组、西药组Smad7表达均显著增加,与模型组比较差异均有统计学意义(P<0.05);中药高剂量组Smad2/3、TGF-β1表达显著降低,与中药低剂量组、西药组比较差异均有统计学意义(P<0.05);中药高剂量组Smad7表达显著升高,与中药低剂量组、西药组比较差异有统计学意义(P<0.05)。【结论】化痰祛瘀中药防治腹膜纤维化的作用与其能上调TGF-β抑制性信号蛋白Smad7的表达,抑制TGF-β受体调控信号蛋白Smad2/3表达有关。

Effect of Phlegm-resolving and Stasis-removing Therapy on TGF-β/Smad Signal Pathway in Peritoneal Fibrosis Rats

Objective To explore the effect of phlegm-resolving and stasis-removing therapy on tumor growth factor beta(TGF-β)/Smad signal pathway in peritoneal fibrosis rats.Methods Sixty healthy SD male rats were equally randomized into 5 groups: blank group,model group,western medicine group,high-and low-dose herbal medicine groups.Peritoneal fibrosis rats model was established firstly,and then the rats in the medication groups were given orally high-dose(50 mg·kg-1·d-1)or low-dose(25 mg·kg-1·d-1)herbal medicine with the actions of resolving phlegm and removing stasis,or benazepril(5 mg·kg-1·d-1) respectively.The rats in the model group and the blank group were given orally water for injection,once per day for 4 weeks.Peritoneal tissue was sampled at the end of the experiment.Immunohistochemical assay was used to examine the expression of phosphorylation-Smad2/3,Smad7 and TGF-β1 in the visceral peritoneum.Results Smad7 expression level was increased in high-,low-dose herbal medicine groups and benazepril group,the difference being significant compared with that in the model group(P<0.05).Smad2/3 and TGF-β1 expression levels were lower and Smad7 expression level was higher in high-dose herbal medicine group than those in low-dose herbal medicine group and benazepril group(P<0.05).Conclusion The preventive and therapeutic mechanism of phlegm-resolving and stasis-removing herbal medicine for peritoneal fibrosis is related with the up-regulation of TGF-β inhibitive signal protein Smad7 expression,and with the down-regulation of TGF-β receptor regulative signal protein Smad2/3 expression.