Effect Of Smoke Exposure On Expressional Level Of HIF-1α And NF-κB In The Lungtissue Of Rats On Pulmonary Hypertension Model

Objective:To study the mechanisms of pulmonary hypertension caused by smoke exposure in researching the effect of smoke exposure on the expressional levels of hypoxia inducible factor1alpha and nuclear factor-kappa B p65in rats lung tissue.Methods:Forty healthy male wistar rats were randomly divided into the control group,smoke exposure4、8、12weeks group.The smoking exposure group rats were put in the self-made fumigating box in to smoke exposure,two times every day, fifteen cigarettes every time and six days one week,exposed four、eight、twelve weeks respectively. The control group only was not exposed to smoking. The mean pulmonary arterial pressure was measured by right-heat catheterization,complete free the heart and lung tissue,and right ventricle hypertrophy index was measured, the lift lung tissue was for-80℃freeze-stored refrigerator and the right lung tissue was embedded in paraffin and sliced.The relative expression of HIF-1α mRNA was detect by real-time fluorescence quantitative PCR and HIF-1α NF-κB p65protein in rat lung tissue were detected by immunohistochemistry in all rats of four groups,analysis the correlation of the index reciprocally.Results:①The mPAP of rats of smoke exposure8weeks group and12weeks group (14.70±1.125、17.83±2.437) were significantly higher than those of the control group and smoke exposure4weeks group (10.67±1.125、11.88±1.536)(Pall<0.01),the mPAP of rats of smoke exposure12weeks group(17.83±2.437) were significantly higher than the8weeks group(14.70±1.125)(P0.01);There were no statistically difference in mPAP in the control group and smoke exposure4weeks group(10.67±1.125、11.88±1.536)(P>0.05).②The right ventricular hypertrophy index in smoke exposure12weeks group(0.26±0.020) were significantly higher than those of the control group(0.22±0.020)(P<0.01);There were no statistically difference in RVHI in the control group and smoke exposure4、8weeks group(0.22±0.020、0.23±0.020、0.24±0.020)(Pall>0.05).③The relative expression of HIF-1α mRNA of rats in smoke exposure8weeks(1.17±0.211)and12weeks(1.36±0.185)groups were significantly higher than those of smoke exposure4weeks(0.92±0.141) and the control groups (0.76±0.137)(Pall<0.05),the relative expression of HIF-1α mRNA of rats in smoke exposure12weeks(1.36±0.185) group was significantly higher than those of the smoke exposure8weeks(1.17±0.211)groups(P <0.01); There were no statistically difference in the relative expression of HIF-1α mRNA in the control group and smoke exposure4weeks group(P>0.05).④The expression of HIF-1α protein in the smoke exposure4、8、12weeks groups(0.204±0.005、0.235±0.004、0.249±0.003) in the pulmonary vascellum smooth muscle were significantly higher than those of the the control group(0.077±0.003)(Pall<0.01);The expression of HIF-1α protein in the smoke exposure8、12weeks groups(0.235±0.004、0.246±0.003) were significantly higher than those of smoke exposure4weeks group(0.204±0.005)(Pall<0.01);The expression of HIF-1α protein in the smoke exposure12weeks groups(0.249±0.003)were significantly higher than those of smoke exposure8weeks group(0.235±0.004)(P<0.01).⑤The expression of NF-κB p65protein in the smoke exposure4、8、12weeks groups(0.478±0.003、0.573±0.003、0.690±0.003) in airway were significantly higher than those of the the control group(0.308±0.005)(Pall<0.01),the smoke exposure8、12weeks groups (0.573±0.003、0.690±0.003)were significantly higher than those of the smoke exposure4weeks group(0.478±0.003)(Pall<0.01),the smoke exposure12weeks group(0.690±0.003) were significantly higher than those of the smoke exposure8weeks group(0.573±0.003)(P<0.01).⑥The mPAP was positively correlated with RVHI (r=0.478, P<0.01); The expressions of HIF-1α protein were positively correlated with mPAP、RVHI、the relative expression of HIF-1α mRNA and the expression of NF-κBp65protein(r=0.688r=0.497、r=0.706、r=0.877,pall<0.01).Conclusion:Smoke exposure8weeks lead to pulmonary arterial hypertension; The expression of HIF-1α in rats lung tissue was higher after smoke exposure4weeks than in the control group, promoted pulmonary vascular remodeling,higher and higher to12weeks, lead to pulmonary arterial hypertension; The expression of NF-κB protein in rats lungtissue was higher in smoke exposure4weeks than in the control group,higher and higher to12weeks,and positively correlated with the expression of HIF-1α, speculating HIF-1α and NF-κB all play an rolei n the mechanisms of pulmonary hypertension caused by smoke exposure.