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目的 探讨转化生长因子α和β１（ＴＧＦα、ＴＧＦβ１） 对肺泡Ⅱ型细胞增生的影响及其作用机制。方法 采用原代培养的成年大鼠肺泡Ⅱ型细胞，加入ＴＧＦα、ＴＧＦβ１ 作用４８ 小时，测定肺泡Ⅱ型细胞３ＨＴｄＲ 掺入量和细胞数量，并用斑点杂交、原位杂交和免疫组化方法检测细胞内细胞周期蛋白Ｄ１（ｃｙｃｌｉｎ Ｄ１） 、细胞周期依赖性激酶４（ＣＤＫ４） ｍＲＮＡ和蛋白的表达。结果 随ＴＧＦα浓度（０．１～１００ ｎｇ／ｍｌ）递增，肺泡Ⅱ型细胞３ＨＴｄＲ掺入量和细胞数量均逐渐增加，呈量效正相关（Ｐ＜ ０．０１）；ＴＧＦα使细胞内ＣＤＫ４ ｍＲＮＡ和蛋白表达均明显增强（ Ｐ＜０．０１） 。随ＴＧＦβ１ 浓度（０．０１～１０ ｎｇ／ｍｌ）递增，肺泡Ⅱ型细胞３ＨＴｄＲ掺入量和细胞数量则逐渐减少，呈量效负相关（ Ｐ＜ ０ ．０１） ；ＴＧＦβ１ 使细胞内ＣＤＫ４ ｍＲＮＡ、ＣＤＫ４ 和ｃｙｃｌｉｎ Ｄ１ 蛋白表达降低（ Ｐ＜０．０５） 。结论 ＴＧＦα和ＴＧＦβ１ 对成年大鼠肺泡Ⅱ型细胞增生有明显的调控作用；ＣＤＫ４ 可能为ＴＧＦα和ＴＧＦβ１ 共同的靶分子，成为调控肺泡Ⅱ型细胞增生的共同信号通路。
Objective To investigate the effect of transforming growth factor-α and β1 (TGFα, TGFβ1) on alveolar type Ⅱ cell proliferation and its mechanism. Methods The primary cultured rat alveolar type II cells were treated with TGFα and TGFβ1 for 48 hours. 3H-TdR incorporation and number of cells in alveolar type Ⅱ cells were measured. Dot blot hybridization, in situ hybridization and immunohistochemistry The expression of cyclin D1, CDK4 and CDK4 mRNA and protein were measured. Results As the concentration of TGF-α increased from 0.1 to 100 ng / ml, 3H-TdR incorporation and number of cells in type Ⅱ cells increased gradually with a positive correlation between quantity and effect (P <0.01) CDK4 mRNA and protein expression were significantly enhanced (P <0.01). With the increasing concentration of TGFβ1 (0.01 ~ 10 ng / ml), 3HTdR incorporation and cell number in type Ⅱ cells decreased gradually with a doseeffective and negative correlation (P <0.01); TGFβ1 increased intracellular CDK4 mRNA, CDK4 and cyclin D1 protein expression decreased (P <0.05). Conclusion TGFα and TGFβ1 can significantly regulate the proliferation of alveolar type Ⅱ cells in adult rats. CDK4 may be a common target of TGFα and TGFβ1, which may be a common signal pathway for the regulation of alveolar type Ⅱ cell proliferation.