汉防己甲素对肺纤维化大鼠肺组织钙-钙调素系统的影响

Effect of tetrandrine on the calcium-calmodulin system of lung tissue in rats of the bleomycin-induced pulmonary fibrosis

目的 探讨汉防己甲素 (Tet)防治肺纤维化的机制。方法 48只SD大鼠一次性气管内注入博莱霉素A5,制备肺纤维化模型 ,随机分为两组 :模型组 (n =2 4 )及Tet组 (n =2 4 ) ,在实验d7、d1 4、d2 8分批处死后作病理切片 ,应用电子计算机图像分析仪进行肺泡炎和肺间质纤维化定量分析 ;采用火焰原子吸收分光光度法及磷酸二酯酶 (PDE)法分析测定各组给药后肺组织钙含量及钙调素活性 ,并与正常对照组 (n =8)比较。结果 模型组肺组织钙含量及钙调素活性较正常组明显增高 (P <0 .0 1 ,P <0 .0 0 1 )。Tet组各期钙含量及钙调素活性均低于模型组 (P <0 .0 1 ) ,组织病理学显示肺泡炎及肺纤维化程度均较模型组明显减轻。结论 Tet防治鼠肺纤维化的机制可能与拮抗钙。

Objective To investigate the mechanism of protective effects of tetrandrine(Tet) on bleomycin-induced pulmonary fibrosis.Methods Forty eight SD rats were replicated into pulmonary fibrosis models by intratracheal injection of bleomycin A5 in one lump , and were then divided into two groups randomly,untreated model group(n=24) and Tet group(n=24). Other eight rats were used as controls. Both model group and Tet group were put to death on the 7th,14th,28th days and their lungs were removed for pathologic examination. The quantitative analysis of alveolitis and fibrosis of the lungs was done by histopathological examination and calmodulin activity in lung tissues with computer-aided image analyser.Total calcium contents were measured with atomic absorption spectrophotometry and phosphodiesterase method and the findings were compared with the controls.Results The calcium contents and calmodulin activity in model group were obviously higher than those in control group(P<0.01, P<0.001);those of Tet group were obviously lower than those of model group at all phases(P<0.01). The degree of alveolitis and fibrosis of the lung by histopathology was obviously reduced than that in the model group.Conclusion The mechanism of the protective effect of Tet on bleomycin-induced pulmonary fibrosis might be related to its antagonism on calcium-calmodulin system.