| 摘要: |
| 目的：研究健脾益气方通过调控间隙连接蛋白（Cx）43干预腹膜透析大鼠腹膜间皮细胞转分化的作用机制。方法：将75只大鼠随机分为5组,即空白组、模型组、中药高剂量组、中药低剂量组、西药组,除空白组大鼠外,其余各组均采用5/6肾切除联合腹腔注射4.25％腹透液复制慢性肾衰竭腹膜纤维化大鼠模型。造模成功后,中药高、低剂量组给予健脾益气方,西药组给予阿托伐他汀钙,模型组给予0.9%氯化钠注射液,空白组不做任何处理。每天灌胃1次,连续4周。干预后光镜观察各组大鼠腹膜结构变化,测量腹膜致密层厚度;免疫组化法及蛋白质印迹法检测Cx43、蛋白激酶B/哺乳动物雷帕霉素靶蛋白（AKt/mTOR）通路和腹膜间皮细胞转分化（EMT）标志蛋白表达。结果：各组大鼠腹膜厚度及Cx43、pAKt、pmTOR、α平滑肌肌动蛋白（α-SMA）、E-钙黏附蛋白（E-cadherin）阳性面积比,空白组与模型组比较,中药高、低剂量组及西药组与模型组比较,中药高剂量组与西药组、中药低剂量组比较,差异均有统计学意义（P<0.05）。各组大鼠腹膜组织Cx43、pAKt、pmTOR、α-SMA、E-cadherin蛋白表达,空白组与模型组比较,中药高剂量组与西药组比较,差异均有统计学意义（P<0.05）。结论：健脾益气方可能通过调控Cx43表达,干预Akt/mTOR信号通路介导的腹膜间皮细胞EMT进程,从而发挥保护腹膜间皮细胞、防治腹膜损伤的作用。 |
| 关键词: 腹膜纤维化 腹膜透析 大鼠 健脾益气方 间隙连接蛋白43 实验研究 |
| DOI： |
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| Interventional effect of spleen-strengthening and Qi-tonifying prescription on peritoneal injury in rats by regulating the gap junction protein connexin 43 |
| MENG Lifeng,YANG Duanyun,SHI Wei |
| (The First Affiliated Hospital of Guangxi University of Chinese Medicine,Nanning 530023,Guangxi,China) |
| Abstract: |
| Objective：To investigate the mechanism of action of spleen-strengthening and Qi-tonifying prescription in the intervention of peritoneal mesothelial cell transdifferentiation in a rat model of peritoneal dialysis by regulating the gap junction protein connexin 43 (Cx43).Methods：A total of 75 rats were randomly divided into blank group,model group,high- and low-dose traditional Chinese medicine (TCM) groups,and Western medicine group.All rats except those in the blank group were given 5/6 nephrectomy combined with intraperitoneal injection of 4.25% peritoneal dialysis solution to establish a rat model of chronic renal failure and peritoneal fibrosis.After successful modeling,the rats in the high- and low-dose TCM groups were given spleen-strengthening and Qi-tonifying prescription,those in the Western medicine group were given atorvastatin calcium,those in the model group were given 0.9% sodium chloride injection,and those in the blank group were not given any treatment.The drugs were given by gavage once a day for 4 consecutive weeks.After intervention,a light microscope was used to observe the change in peritoneal structure and measure the thickness of peritoneal dense layer;immunohistochemistry and Western blot were used to measure the expression of Cx43,the protein kinase-B/mammalian target of rapamycin (Akt/mTOR) pathway,and marker proteins for the epithelial-to-mesenchymal transdifferentiation (EMT) of peritoneal mesothelial cells.Results：There were significant differences in peritoneal thickness and positive area ratios of Cx43,phosphorylated AKt (pAKt),phosphorylated mTOR (pmTOR),alpha-smooth muscle actin (α-SMA),and epithelial cadherin (E-cadherin) between the blank group and the model group,between the high- and low-dose TCM groups/Western medicine group and the model group,and between the high-dose TCM group and the Western medicine group or low-dose TCM group (P＜0.05).There were significant differences in the protein expression of Cx43,pAKt,pmTOR,α-SMA,and E-cadherin in the peritoneal tissue between the blank group and the model group and between the high-dose TCM group and the Western medicine group (P＜0.05).Conclusion：Spleen-strengthening and Qi-tonifying prescription exerts a protective effect on peritoneal mesothelial cells and plays a role in the prevention and treatment of peritoneal injury by regulating the expression of Cx34 and the EMT process of peritoneal mesothelial cells mediated by the Akt/mTOR signaling pathway. |
| Key words: peritoneal fibrosis peritoneal dialysis rat spleen-strengthening and Qi-tonifying prescription connexin 43 experimental study |
