胰岛素样生长因子结合蛋白家族在肺动脉高压模型大鼠肺动脉平滑肌细胞中的表达模式

The expression profile of IGFBP family in pulmonary artery smooth muscle cells of rats with pulmonary hypertension

目的探讨胰岛素样生长因子结合蛋白（IGFBP）在由野百合碱诱导的肺动脉高压大鼠的肺动脉平滑肌细胞中的表达变化。方法取健康成年SD大鼠26只,随机分成2组：肺动脉高压（PAH）组,腹腔注射野百合碱,剂量为60 mg/kg;正常（C）组,腹腔注射生理盐水。于4周后超声检测肺动脉平均压力,取肺组织做HE染色,倒置显微镜观察,测量70～100μl肺血管中膜百分比,以此评定中膜厚度。原代培养肺动脉平滑肌（PASMC）细胞,RT-PCR检测IGFBP家族成员m RNA表达,Western blot检测IGFBP家族蛋白表达。结果给药处理4周后,肺动脉高压组的平均肺动脉压力（75.69±6.726）mm Hg,高于对照组（34.58±2.491）mm Hg。右心室/（左心室＋室间隔）比值肺动脉高压组（0.40±0.036）显著高于对照组（0.22±0.024）,肺小血管中膜厚度百分比肺动脉高压组（0.25±0.042）高于对照组（0.19±0.040）。肺动脉高压组与对照组比较,IGFBP-1、IGFBP-2、IGFBP-4的m RNA表达水平无明显统计学差异;IGFBP-3、IGFBP-5、IGFBP-6的m RNA表达肺动脉高压组显著高于对照组。IGFBP-3、IGFBP-5、IGFBP-6蛋白表达肺动脉高压组亦显著高于对照组。结论由野百合碱诱导的肺动脉高压大鼠平滑肌细胞中,IGFBP家族中某些蛋白发生显著变化。

Objective To study expression profiles of IGFBPs in SD rats pulmonary arterial smooth muscle cells which with pulmonary arterial hypertension induction by monocrotaline. Methods Rats were randomly assignment into two groups, one group were treated with physiological saline as control（C）,the other group were injected with Monocrotaline（MCT） as pulmonary arterial hypertension（PAH）. Mean pulmonary arterial pressure（MPAP） and rough ventricle systolic pressure（RVSP） were determined after treatment 4 weeks by cardiac ultrasound machine. The m RNA levels of IGFBP in rats pulmonary arterial smooth muscle cells（PASMCs） that isolated from pulmonary arterial were detected by q RT-PCR. The expression of IGFBP in PASMC was detected by Western blot methods. Results Four weeks after treatment, the MPAP in PAH group were higher than control group. The PAH model leads to a significant increase in RV/（LV＋S） and pulmonary artery media thickness. There was no change in IGFBP-1, IGFBP-2,IGFBP-4 between two groups, but there was significantly difference in IGFBP-3, IGFBP-5, IGFBP-6.Conclusion There exists different expression of IGFBP protein in PASMC isolated from PAH rats.