PPAR-γ通过PI3K/Akt及NF-κB通路调控猪颈动脉支架植入术后的血管重构

PPAR-γ regulates vascular remodeling after pig carotid artery stent implantation through PI3K/Akt and NF-κB pathway

目的观察过氧化物酶体增殖物激活受体-γ(peroxisome proliferator activated receptors-γ,PPAR-γ)在猪颈动脉支架植入术后血管重构中的作用。方法将12只小型猪分为正常对照组(n=4)和介入手术组(n=8),介入手术组采用猪颈动脉支架植入建立动物模型,分为支架组(n=4)和罗格列酮(ROSI)组(n=4)。术后3个月,应用数字减影血管造影(digital subtraction angiography,DSA)技术及HE染色评估血管形态学变化,应用免疫组织化学方法检测p-Akt及NF-κB的表达变化,应用Western blot方法检测支架段血管PPAR-γ、Akt、p-Akt及NF-κB的表达变化。结果①猪颈动脉DSA和HE染色结果发现支架组血管狭窄较ROSI组明显(P<0.01)。②免疫组织化学染色结果发现支架组颈动脉血管p-Akt和NF-κB表达较正常对照组明显增加(P<0.01),ROSI组颈动脉血管p-Akt和NF-κB表达较支架组明显降低(P<0.01)。③Western blot检测结果显示:支架组PPAR-γ蛋白表达水平较正常对照组明显降低(P<0.01),NF-κB和p-Akt蛋白表达水平较正常对照组明显增加(P<0.05);ROSI组PPAR-γ蛋白表达水平较支架组明显增加(P<0.01),NF-κB和p-Akt蛋白表达水平较支架组明显降低(P<0.01);Akt在正常对照组、支架组和ROSI组中的蛋白表达量差异无统计学意义(P>0.05)。结论 PPAR-γ可能通过调节PI3K/Akt及NF-κB的表达,从而改善支架植入术后的血管重构。

Objective To determine the role of peroxisome proliferator activated receptors-γ （PPAR-γ） in swine vascular remodeling after carotid artery stent implantation. Methods Totally 12 miniature pigs were randomly divided into normal control group （n=4） and intervention group （n=8）. The animals of intervention group were adopted to establish the animal model of carotid artery stenting, and then randomly divided into stent subgroup （n=4） and rosiglitazone treatment （ROSI） subgroup （n=4）. In 3 months after surgery, digital subtraction angiography （DSA） and HE staining was used to assess vascular morphology, immunohistochemical staining was applied to detect the expression of P-akt and NF-κB, and Western blotting was employed to detect the expression of PPAR-γ, Akt, p-Akt and NF-κB. Results DSA and HE staining demonstrated that vascular stenosis was more severe in the stent subgroup than the ROSI group （P〈0.01）. Immunohistochemical staining showed that the expression of p-Akt and NF-κB were significantly increased in the carotid artery stent groups than normal control group （P〈0.01）, and that in ROSI subgroup was significantly lower than in the stent subgroup （P〈0.01）. Western blot analysis showed that the protein expression level of PPAR-γ was significantly lower （P〈0.01）, and those of NF-κB and p-Akt were obviously higher in the stent subgroup than the normal control group （P〈0.05）, while that of PPAR-γ was significantly enhanced （P〈0.01）, and those of NF-κB and p-Akt were markedly reduced in the ROSI subgroup than in the stent subgroup （P〈0.01）. However, there was no significant difference in the protein expression of Akt in normal control group, stent subgroup and ROSI subgroup （P〉0.05）. Conclusion PPAR-γ might mediate the expression of PI3K/Akt and NF-κB, and then improve the vascular remodeling after stent implantation.