The Clinical Research Of TLR-4、NF-κB And AP-1in Pulmonary Vascular Remodeling With Chronic Pulmonary Disease

Objective:In order to investigate the effect of Toll-like receptor4(TLR-4), nuclear factor-Kb(NF-κB) and activator protrin-1(AP-1)in pulmonary vascular remodeling in patients with copd by detecting the expression of TLR-4, NF-κB and AP-1of pulmonary tissue.Methods:Specimens were collected from thoracic surgery patient in our hospital, according to their lung function,40male lung carcinoma patients, they were divided into2groups:control group and COPD stable group, with20patients in each group. The lung specimens were obtained from adjacent noncancerous tissue. Preoperative lung functional measurements, partial pressure of oxygen (PaO2) and smoking index were performed in all the patients. Morphmetric characteristic of pulmonary artery remodeling was observed with HE staining under microscope and Mosson staining, the wall area to total vascular area percentage (WA%), the wall thickness in the percentage of vessel diameter (WT%) and wall thickness of the collagen fibers were measured, the expression of TLR-4, NF-κB, AP-1and proliferating cell nuclear antigen (PCNA) of pulmonary tissue were measured by means of immunohisto-chemistry.Results:(1)Compared with control group, inflammation cells of arteries walls in COPD group increased, the degree of arterial inflammation, WA%, WT%and wall thickness of the collagen fibers were significantly increased in COPD group(.P<0.01)(2) Expression of TLR-4, NF-κB and AP-1in the pulmonary arteries epithelial cells were significantly higher in COPD group(22.58%±4.49%)(32.18%±5.81%)(17.91%±3.38%)than that in control group (15.40%±3.21%)(20.49%±4.02%)(8.08%±2.07%)(P<0.01).Expression of PCNA in the pulmonary arteries smooth muscle cells were significantly higher in COPD group (20.54%±4.97%) than that in control group (9.32%±2.42%)(P<0.01).(3) The IOD of TLR-4, NF-κB and AP-1in the pulmonary arteries were higher in COPD group (1104.25±280.10)(1518.60±256.54)(1240.95±215.42)(1328.25±231.88) than that in control group (714.20±174.28)(828.05±171.84)(539.25±185.11)(621.95±202.49)(P<0.01).(4) Correlation analysis:Expression of TLR-4in epithelial cells was positively correlated with expression of NF-κB and AP-1in epithelial cells, PCNA expression in smooth muscle cells,degree of arterial inflammation, WA%,WT%and wall thickness of the collagen fibers(0.846、0.792,0.833,0.784,0.826,0.754,0.770, P<0.01). Expression of NF-κB in epithelial cells was positively correlated with AP-1expression in epithelial cells, PCNA expression in smooth muscle cells.degree of arterial inflammation, WA%,WT%and wall thickness of the collagen fibers(0.857、 0.823,0.728,0.854,0.867,0.849, P<0.01). Expression of PCNA in smooth muscle cells was positively correlated with degree of arterial inflammation, WA%,WT%and wall thickness of the collagen fibers(0.696,0.841,0.846,0.831, P<0.01). The IOD of TLR-4in the pulmonary arteries was positively correlated with that of NF-κB, AP-land PCNA in the pulmonary arteries, degree of arterial inflammation, WA%,WT%and wall thickness of the collagen fibers(0.804,0.730,0.785,0.777,0.840,0.731,0.825, P<0.01).The degree of arterial inflammation was positively correlated with WA%,WT%,wall thickness of the collagen fibers and the IOD of PCNA in the pulmonary arteries (0.768,0.649,0.706,0.686,P<0.01).Conclusion:There is a significant pulmonary inflammation and vascular muscularization in COPD. The increased expression of TLR-4, NF-κB and AP-lin lung tissue may participate in pulmonary vascular remodeling by promoting inflammation reaction inducing vascular smooth muscle cells proliferation and collagen deposition.