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目的:观察小G蛋白Rho相关激酶(Rock-1)基因在大鼠缺氧性肺动脉高压(HPH)肺组织中的表达规律,探讨法舒地尔(fasudil)对HPH的预防作用。方法:72只SD大鼠随机分为缺氧模型组(H组)和缺氧+fasudil预防组(fasudil组),对照组(C组)。采用常压间断缺氧法复制大鼠HPH模型,右心导管测平均肺动脉压力(mPAP),计算右心室(RV)/[左心室+室间隔(LV+S)]的重量比值作为右心肥厚指数,并用RT-PCR方法测定肺组织Rock-1及平滑肌肌动蛋白(α-SMA)mRNA表达水平。结果:mPAP在缺氧7天后明显增高(P<0.01),并随缺氧时间的延长,进一步升高。右心肥厚指数在H组第7天开始升高,第14天与C组比较差异有显著性(P<0.01)。与H组比较,fasudil组mPAP及右心肥厚指数均明显降低(P<0.01)。Rock-1基因在HPH发生早期即明显上调,第7天达高峰后维持于较高水平。α-SMA基因表达第7天明显上调,第14天达高峰,至模型后期仍高于基础表达;Rock-1基因表达较α-SMA提前达到高峰,二者呈显著正相关(r=0.883,P<0.05);fasudil组两基因表达水平均较H组明显降低(P<0.01)。结论:Rock-1基因在HPH大鼠肺组织中出现了明显表达异常,法舒地尔能显著降低mPAP,改善右心室肥厚,并可能通过抑制肺组织Rock-1基因表达发挥作用。
OBJECTIVE: To observe the expression of Rock-1 gene in the lung of hypoxic pulmonary hypertension (HPH) rats and to explore the preventive effect of Fasudil on HPH. Methods: Seventy-two SD rats were randomly divided into hypoxia model group (H group) and hypoxia + fasudil prevention group (fasudil group) and control group (C group). The rat model of HPH was reproduced by intermittent anoxia at normal pressure and the mean pulmonary artery pressure (mPAP) was measured by right heart catheter to calculate the weight ratio of right ventricle (RV) / left ventricular + interventricular septum (LV + S) Index, and the expression of Rock-1 and α-SMA mRNA in lung tissue were determined by RT-PCR. Results: mPAP increased significantly after 7 days of hypoxia (P <0.01), and further increased with the prolongation of hypoxia. Right ventricular hypertrophy index increased from the 7th day in group H, and there was a significant difference between the 14th day and the C group (P <0.01). Compared with H group, mPAP and right ventricular hypertrophy index in fasudil group were significantly decreased (P <0.01). Rock-1 gene was significantly up-regulated in the early stage of HPH, and maintained at a high level on the seventh day after reaching the peak. The expression of α-SMA was significantly increased on the 7th day and peaked on the 14th day, and still higher than the basal expression at the late stage of the model. Rock-1 gene expression peaked ahead of α-SMA (r = 0.883, P <0.05). The expression of both genes in fasudil group was significantly lower than that in H group (P <0.01). Conclusion: Rock-1 gene is abnormally expressed in the lung tissue of HPH rats. Fasudil can significantly reduce mPAP and improve right ventricular hypertrophy, and may play a role in the inhibition of Rock-1 gene expression in lung tissue.