低分子肝素联合肺泡表面活性物质对幼年大鼠急性肺栓塞的治疗研究

The effect of low molecular weight heparin combined with pulmonary surfactant on acute pulmonary embolism in young rats

目的探讨低分子肝素(LMH)联合肺泡表面活性物质(PS)对幼年大鼠急性肺栓塞的治疗作用。方法将雄性4周龄SD大鼠45只随机分为5组,对照组、肺栓塞组、LMH组、PS组、LMH-PS组,每组9只。除对照组外,其余各组均采用明胶海绵颗粒溶液经颈静脉注射制作急性肺栓塞模型;LMH组在术后给予LMH 0.01 ml/kg,2次/d皮下注射,PS组术后气管内灌注PS 120 mg/kg,1次/d。LMH-PS组则联合应用上述两种干预方式。对照组采用等量生理盐水颈静脉注射。各组均在术后1、4、7 d检测动脉血气、肺动脉压力(m PAP)及右心室压力(RVP)、肺组织内皮素-1(ET-1)和基质金属蛋白酶9(MMP-9)基因及蛋白表达水平和肺组织切片苏木精-伊红(HE)染色。结果各组大鼠血气分析Pa O2在1、4、7 d时的差异均具有统计学意义(P均<0.05)。1 d和4 d时,LMH-PS组大鼠Pa O2分别为(85.4±6.8)和(87.8±4.7)mm Hg,显著高于栓塞组、LMH组和PS组,但低于对照组,差异均有统计学意义(P<0.05)。LMH-PS组的m PAP在术后1 d时与对照组差异具有统计学意义(18.3±1.9 vs 16.3±1.5,P<0.05),而在4 d和7 d时,两组差异已无统计学意义(P>0.05),但LMH-PS组大鼠肺动脉压(m PAP)仍显著低于其余三组,差异有统计学意义(P<0.05)。各组ET-1 m RNA及蛋白表达水平在4 d、7 d时差异均具有统计学意义(P<0.05),LMH-PS组ET-1 m RNA及蛋白水平在术后4 d时迅速下降,低于其余3组,差异均有统计学意义(P均<0.05),但与对照组的差异无统计学意义(P>0.05)。各组MMP-1 m RNA及蛋白水平在4 d和7 d时的差异也均具有统计学意义(P<0.05)。结论 LMH联合PS能够有效治疗幼年大鼠的急性肺栓塞。

Objective To investigate the effect of low molecular weight heparin （LMH） combined with pulmonarysurfactant （PS） on acute pulmonary embolism in young rats. Methods Forty-five 4-week-old male SD rats were randomlydivided into control group, pulmonary embolism group, LMH group, PS group, LMH-PS group, 9 rats each. Except in the controlgroup, the gelatin sponge particles were injected through jugular vein to make acute pulmonary embolism model. After theinjection, LMH group was injected subcutaneously with 0.01 ml LMH /kg twice a day; PS group was perfused intratracheallywith 120 mg PS/kg , once a day; LMH-PS group was treated with both LMH and PS. The control group was administratedthe same volume of normal saline through jugular vein. On day 1, 4, 7 after injection, the arterial blood gas was analyzed, thepulmonary artery pressure （mPAP） and right ventricular pressure （RVP） were measured, the protein and gene expression levelsof ET-1, MMP-9 were detected, and hematoxylin and eosin stain of lung tissue was performed. Results There were statisticaldifferences in PaO2 among the 5 groups on day 1, 4 and 7 （P all 〈 0.05）. On day 1 and 4, the level of PaO2 in LMH-PS was85.4±6.8 mmHg and 87.8±4.7 mmHg which were significantly higher than in pulmonary embolism group, LMH group andPS group, but lower than in control group （P all 〈 0.05）. There was significant difference in the mPAP on day 1 after injectionbetween LMH-PS group and control group （P 〈 0.05）, and then there were no differences on day 4 and 7 between two groups（P all 〉 0.05）. However, the mPAP was still significantly lower in LMH-PS group than in other three groups （P 〈 0.05）. Theexpression levels of mRNA and protein of ET-1 and MMP-1 on day 4 and 7 were statistically different among the 5 groups （Pall 〈 0.05）. Moreover, the expressions of mRNA and protein of ET-1 were lower in LMH-PS group than in other three groupsexcept the control group. Conclusion LMH combined with PS could effectively treat acute pulmonary embolism in young rats.