补肾益肺消癥方对特发性肺纤维化大鼠Caspase-12信号通路关键分子基因和蛋白表达的影响

Effects of Bushen Yifei Xiaozheng Decoction on the expression of key molecular genes and proteins in Caspase-12 signaling pathway in IPF rats

目的探讨补肾益肺消癥方干预特发性肺纤维化大鼠含半胱氨酸的天冬氨酸蛋白水解酶(Caspase)-12信号通路关键分子基因和蛋白表达的作用机制。方法以博莱霉素造大鼠肺纤维化模型。吡非尼酮作为阳性对照药物,补肾益肺消癥方分别于造模中(预防组)、造模后(治疗组)及实验全程(防治组)进行干预。Masson染色观察大鼠病变肺组织纤维化改变的程度,Western blot、Real-time PCR检测病变肺组织中Caspase-12信号通路相关分子基因与蛋白表达的改变。结果阳性对照组和中药各组肺泡结构轻度改变,有少量胶原纤维沉积,纤维化程度较模型组明显改善。模型组大鼠肺组织中Caspase-12通路基因及蛋白表达比正常组明显升高(P<0.05),阳性组及中药各组Caspase-12通路基因及蛋白表达较模型组明显降低(P<0.05或P<0.01),其中中药防治组效果更优。结论补肾益肺消癥方可以通过干预Caspase-12通路关键分子的表达,调控肺泡上皮细胞内质网应激反应,延缓和抑制特发性肺纤维化病理改变进程。

Objective To investigate the effects lung-boosting stasis-resolving decoction） on the of Bushen Yifei Xiaozheng Decoction （ kidney-tonifying expression of key genes and proteins in Casepase-12 signaling pathways in rats with idiopathic pulmonary fibrosis （IPF）. Methods IPF was induced with bleomycin in rats except for the normal group. Pirfenidone was used as positive control, while Bushen Yifei Xiaozheng Decoction （TCM） was administered during （TCM preventive group） and after （TCM treatment group） the model established and throughout the whole experiment （TCM preventive and treat- ment group）. Pathological change in the rat lungs was observed with Masson staining, meanwhile the ex- pression of molecular genes and proteins involved in Caspase-12 signaling pathways was detected by using Western blot and Real-time PCR. Results Masson staining revealed that the degree of fibrosis in TCM groups improved significantly and alveolar structure changed little. Protein and gene expression of Caspase-12 pathway in the model group was higher than those of normal group （P 〈 0.05 ）. In addition, the protein and gene expression of pirfenidone group and TCM groups were less than the model group （P 〈 0.05 or P 〈 0.01 ）, especially TCM preventive and treatment group. Conclusion Bushen Yifei Xi- aozheng Decoction could inhibit the process of pulmonary fibrosis via acting on the gene expression of Caspase-12 pathway and releasing the endoplasmic reticulum stress.