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目的:研究异烟肼(isoniazid,INH)对大鼠成骨细胞(osteoblasts,OB)增殖、碱性磷酸酶(Alkalinephosphatase,ALP)活性和Ⅰ型胶原合成的影响。方法:分离、培养新生SD大鼠头盖骨OB,分别加入不同浓度的INH(1、10、20、40、60、100、1000滋g/ml)共同培养96h,对照组不加INH,分别采用四唑盐(MTT)比色实验、ALP活性测定法和3H-Proline(3氢-脯氨酸)法测定OB增殖、ALP活性和Ⅰ型胶原合成的情况。结果:与对照组比较,INH在60滋g/ml即可抑制大鼠OB增殖(P<0.05),40滋g/ml时大鼠成骨细胞ALP活性明显下降(P<0.05),20滋g/ml时大鼠成骨细胞Ⅰ型胶原合成(P<0.05)明显减少,且都随浓度增加抑制作用加强。结论:INH在较低浓度时对OB增殖、ALP活性和Ⅰ型胶原合成即有抑制作用,故在骨结核治疗中应该严格控制药物剂量,特别是在局部用药时。
OBJECTIVE: To study the effects of isoniazid (INH) on the proliferation, alkaline phosphatase (ALP) activity and type I collagen synthesis of osteoblasts in rats. Methods: The skull OB of newborn SD rats were isolated and cultured, and incubated with different concentrations of INH (1, 10, 20, 40, 60, 100 and 1000 μg / ml) for 96 h respectively, without INH in control group, MTT assay, ALP activity assay and 3H-Proline assay were used to determine OB proliferation, ALP activity and type I collagen synthesis. Results: Compared with the control group, INH could inhibit the proliferation of rat OB (P <0.05) at 60 μg / ml, ALP activity of osteoblasts decreased significantly at 40 μg / ml (P <0.05) The collagen type Ⅰ collagen synthesis (P <0.05) of rat osteoblasts decreased significantly at g / ml, and all of them were inhibited with increasing concentration. CONCLUSIONS: INH inhibits OB proliferation, ALP activity and type I collagen synthesis at lower concentrations. Therefore, INH should be given a controlled dose of drug, especially during topical application.