不同剂量低分子肝素对幼年大鼠急性肺栓塞的治疗及肺动脉内膜增生抑制作用

摘要

目的：探讨不同剂量低分子肝素对幼年大鼠急性肺栓塞的治疗及肺动脉内膜增生抑制作用。方法将90只幼年SD大鼠随机分为假手术组，肺栓塞组，低、中和高剂量低分子肝素组（LLMH、MLMH和HLMH组）。除假手术组外，各组均制作急性肺栓塞模型，LLMH、MLMH、HLMH组在术后分别给予低分子肝素0.005、0.01、0.02mL/kg，2次/d皮下注射，假手术组予生理盐水注射。各组于术后7d、14d和28d检测动脉血气、肺动脉压力（mPAP）、右心室压力（RVP）、肺动脉管壁面积/管面积、管壁厚/管外径、肺组织PDGF-B和MCP-1基因及蛋白表达，肺组织HE染色后行病理检查。结果28d时，MLMH组肺组织病理改变较轻。7d、14d和28d时，MLMH组大鼠PaO 2低于假手术组，高于栓塞组、LLMH组，差异均有统计学意义（P < 0.05）。7d、14d和28d时，MLMH组的肺组织PDGF-B和MCP-1基因及蛋白表达水平与假手术组的差异无统计学意义（P > 0.05），但低于其余3组（P均< 0.05）。7d、14d和28d时，MLMH组的mPAP与假手术组的差异无统计学意义（P > 0.05），但低于其余3组（P均< 0.05）；28d时，MLMH组的RVP与假手术组的差异无统计学意义（P > 0.05），但低于其余3组（P均< 0.05）；28d时MLMH组大鼠管壁面积/管面积值、管壁厚/管外径值与假手术组的差异也无统计学意义（P > 0.05）。结论中等剂量低分子肝素更能有效的改善大鼠急性肺栓塞和抑制肺动脉内膜增殖。%Objectives To investigate the effect of different dosages of low molecular weight heparin on acute pulmonary embolism and inhibition of pulmonary intimal hyperplasia in immature rats. Methods 90 male immature SD rats were randomly divided into ifve groups: sham group, pulmonary embolism group, low-low molecular heparin group (L-LMH), medium-low molecular heparin group (M-LMH) and high-low molecular heparin group (H-LMH). The model of acute pulmonary embolism was established through jugular vein injection with gel-foam solution. The rates in the L-LMH, M-LMH, H-LMH groups were treated with low molecular weight heparin by subcutaneous injection after surgery with a dosage of 0 . 005 ml/kg, 0 . 01 ml/kg, 0 . 02 ml/kg, twice a day. Animals in the control group were given saline injection. Arterial blood gas, pulmonary artery pressure (mPAP), right ventricular pressure (RVP), wall area/tube area, wall thickness/tube diameter, and the expression of PDGF-B and MCP-1 at gene and protein levels in lung tissue were detected on the 7 th ( 7 d), 14 th ( 14 d) and 28 th ( 28 d) after opration. Results There were signiifcant differences of PaO 2 among 5 groups on 7 d, 14 d and 28 d. PaO 2 in group M-LMH ( 105 . 1 ± 4 . 6 mm Hg) were signiifcantly higher than that of embolization group, L-LMH, but not H-LMH group at 28 d. mPAP of M-LMH group was lower than that in the other three intervention groups, but showed no signiifcant difference compared with sham group (P >0 . 05 ). There were signiifcant differences of RVP on 7 d and 14 d. PDGF-B, MCP-1 of M-LMH group were signiifcantly lower compared with the other three intervention groups (P < 0 . 05 ), but showed no signiifcant difference compared with sham group (P >0 . 05 ). Wall area/tube area, wall thickness/tube diameter scores of M-LMH group had no signiifcance differences compared with sham group on 28 d (P > 0 . 05 ). Conclusion Medium dose of low molecular weight heparin could ameliorate the acute pulmonary embolism and inhibit the proliferation of pulmonary arteries in rats.