COPD肺动脉平滑肌细胞PPAR—γ表达、增殖／凋亡失衡与肺血管重塑关系的研究

Effect of PPAR-γ,proliferation and apoptosis on pulmonary vascular remodeling of COPD

目的通过对COPD肺动脉PPAR-γ表达、细胞增殖及凋亡的研究，探讨PPAR-γ、增殖凋亡失衡在血管重塑中的作用及相互关系。方法将90例因肺鳞癌行手术切除的男性患者分为COPD组及非COPD组，取术后无肿瘤浸润的肺组织，HE染色光镜下测定血管壁横断面积占管径总面积百分比（WA％）及管壁厚度占血管外径百分比（wT％）；免疫组织化学方法检测肺动脉PPAR-γ及PCNA表达情况，原位断口DNA碎片标记（TUNEL）技术检测肺动脉平滑肌凋亡。结果COPD组肺小动脉管壁增厚、管腔狭窄，WA％及wT％均高于非COPD组，差异有统计学意义（t=-3．95、-7．14，P〈0．01），呈现血管重塑现象；COPD组PPAR-γ阳性率为（10．74±8．81）％，非COPD组为（28．22±15．08）％，2组差异有统计学意义（t=5．48，P=0．00）；COPD组增殖指数（PI）[（26．81±5．57）％]较非COPD组[（9．35±4．70）Yoo]明显增高，差异有统计学意义（t=-5．87，P=0．00）；COPD组凋亡指数（AI）[（4．50±1．20）％]较非COPD组[（6．71±1．48）％]降低，差异有统计学意义（t=2．37，P=0．02）；COPD组增殖凋亡比（PI／AI）[（4．59±1．60）％]较非COPD组[（1．36±0．79）％]增高，差异有统计学意义（t=-4．28，P=0．00）。PPARγ与肺血管重塑wA％、wT％呈负相关（r=-0．705、-0．785，P〈0．01），与AI呈正相关（r=0．501，P=0．001），与PI／AI无明显相关（r=-0．152，P=0．348）。结论PPAR—γ低表达及增殖凋亡失衡在COPD肺血管重塑中发挥重要作用，PPAR-γ促进细胞凋亡。

Objective To investigate possible effect of PPAR-γ, proliferation and apoptosis on pulmonary artery reconstruction,and the relationship between these factors. Methods Enrolled 90 male patients who undergo surgery for squamous cell carcinoma,and divided them into COPD group and non- COPD group based on lung function,45 cases in each group. Taken peripheral lung tissues without tumor infiltrated after lobeetomy,and measured the WA% （percentage of wall area to total vascular area） and WT% （percentage of wall thickness to vessel diameter） through Hematoxylin Eosin （HE） staining under light microscope. Measured the expression of PPAR-γ, proliferation and apoptosis by irnmunohistochemistry and TUNEL technology. Results WA% and WT% of COPD group were significantly higher than that of non-COPD group （ t = -3.95.--7.14, P 〈 0.01）, showed wall thickening and luminal stenosis, and represented apparent revascularization phenomenon. Expression of PPAR-γ in COPD group [（10.74±8.81） %] were significantly lower than that of non-COPD group [（28.22± 15.08） %], （ t = 5.48, P = 0.00）. PI of COPD group [（26.81 ± 5.57） %] were apparently higher than non-COPD group [（9.35±4.70） %],（ t =-5.87, P =0.00）. AI of COPD group [（4.50± 1.20） % ] were lower than non-COPD [ （6.71±1.48） % ], （ t = 2.37, P = 0.02）. PI/AI of COPD group [（4.59± 1.60） %] were significantly higher than that of non-COPD group [（1.36±0.79） %], （t =-4.28, P = 0.00）. PPAR-γ displayed negative correlation with WA % ,WT% which reflect the degree of revascularization （r=-0.705,-0.785, P =0.01）,positive correlation with AI （r =0.501, P = 0. 001） ,and unrelated with PI/AI （ r = -0. 152, P = 0. 348）. Conclusions Low expression of PPAR γ and the imbalance between proliferation and apoptosis of pulmonary artery smooth muscle cells （PASMCs） contributed to the pulmonary artery revascularization of COPD, and PPAR-γ may promote apoptosis of PASMCs.