载脂蛋白E基因敲除模型小鼠转化生长因子β1表达与尼古丁的刺激

背景：研究表明尼古丁可以诱导动脉粥样硬化，但其具体作用机制尚不明确。 目的：探讨不同剂量尼古丁刺激下，载脂蛋白E基因敲除小鼠主动脉粥样斑块形成与外周血转化生长因子β1水平的关系。 方法：载脂蛋白E基因敲除小鼠腹膜下注射2种不同剂量的尼古丁2 mg/(kg?d)及0.5 mg/(kg?d)]12周，对照组注射等量生理盐水。用ELISA法检测外周血转化生长因子β1水平，苏木精-伊红染色观察动脉粥样斑块的病理变化。 结果与结论：尼古丁干预12周后，低剂量尼古丁组的外周血转化生长因子β1水平低于对照组(P < 0.05)，高剂量尼古丁组的外周血转化生长因子β1水平低于对照组及低剂量尼古丁组(P < 0.05)。高剂量尼古丁组的血管狭窄程度最严重，低剂量尼古丁组次之，对照组最低，各组间比较差异均具有显著性意义(P < 0.05)。低剂量尼古丁组及高剂量尼古丁组的斑块个数多于对照组(P < 0.05)，高剂量尼古丁组的斑块个数与低剂量尼古丁组比较差异无显著性意义 (P > 0.05)；血管狭窄率与转化生长因子β1水平呈负相关(r=-0.920，P =0.000)。结果提示尼古丁刺激增加载脂蛋白E基因敲除小鼠动脉粥样硬化斑块数量，这种作用可能与尼古丁抑制转化生长因子β1水平相关。

Relationship between nicotine stimulation and transforming growth factor-beta 1 expression in apolipoprotein E gene knockout mice

BACKGROUND:Studies have shown that nicotine can induce atherosclerosis. But its specific mechanisms remain unclear. OBJECTIVE:To explore the relationships between the formation of atherosclerotic plaque and the level of peripheral blood transforming growth factor-beta 1 in apolipoprotein E gene knockout mice following the stimulation of different doses of nicotine METHODS:ApoE gene knockout mice were peritoneally injected with two different doses of nicotine (2 and 0.5 mg/kg/d) for 12 weeks as high-dose nicotine group and low-dose nicotine group, respectively. The mice of the control group were injected with an equal volume of normal saline. The level of peripheral blood transforming growth factor-beta 1 was detected by enzyme-linked immunosorbent assay, and pathological changes of atherosclerotic plaque were observed by hematoxylin-eosin staining. RESULTS AND CONCLUSION:After 12 weeks of nicotine treatment, the level of peripheral blood transforming growth factor-beta 1 in the low-dose nicotine group was lower than that in the control group (P < 0.05). The level of peripheral blood transforming growth factor-beta 1 in the high-dose nicotine group was lower than that in the control group and low-dose nicotine group (P < 0.05). In addition, the degree of vascular stenosis in the high-dose nicotine group was the most serious followed by the low-dose nicotine group and the control group. There was significant difference among the three groups (P < 0.05). Besides, the number of plaques in the low-dose and high-dose nicotine groups was more than that in the control group (P < 0.05). There was no significant difference in the number of plaques between the low-dose nicotine group and high-dose nicotine group (P > 0.05). Moreover, there was a negative correlation between vascular stenosis rate and transforming growth factor-beta1 level (r=-0.920, P=0.000). There results suggest that nicotine stimulation can increase the number of atherosclerotic plaques in ApoE gene knockout mice, which may be related to the inhibitory effect of nicotine on transforming growth factor-beta1 level.