不同剂量银杏叶提取物对野百合碱所致肺动脉高压的作用效果研究

Study on the effect of different doses of Ginkgo biloba extract on monocrotaline-induced pulmonary arterial hypertension

目的研究针对野百合碱所致的肺动脉高压在不同剂量银杏叶提取物(GBE)作用下的效果,测定肺组织血管活性物质内皮素-1(ET-1)、一氧化氮合成酶(eNOS)的表达。方法依随机数字表将50只雄性SD大鼠分为五组:正常对照组(C组)、肺动脉高压模型组(M组)、GBE低剂量治疗组(G1组,40 mg/kg)、GBE中剂量治疗组(G2组,60 mg/kg)和GBE高剂量治疗组(G3组,80 mg/kg),每组各10只。测定大鼠右心房压(RAP)、右心室收缩压(RVSP)、平均肺动脉压(mPAP)和右心室肥厚指数(RVHI)。HE染色观察肺小动脉的组织结构,计算直径50~150μm肺动脉的中膜厚度占血管外径百分比(MA%)、血管中层面积与血管总面积比值(MV%)。免疫组化测定大鼠肺组织中ET-1和eNOS的表达。结果与M组比较,三个治疗组大鼠的RAP、mPAH、RVSP、RVHI和MA%、MV%均下降,差异有统计学意义(P<0.05);三个治疗组间,仅G3组的RAP、mPAH和MV%与G1组比较,差异有统计学意义(P<0.05)。在eNOS中,五组eNOS表达高低:C组>G3组>G1组>G2组>M组,三个治疗组的eNOS表达均高于M组,差异有统计学意义(P<0.05);治疗组中G3组的eNOS表达分别与G1、G2组比较,差异均有统计学意义(P<0.05)。在ET-1中,五组ET-1表达高低:M组>G1组>G2组>G3组>C组,三个治疗组的ET-1表达均低于M组,差异有统计学意义(P<0.05);治疗组中G3组的ET-1表达分别与G1、G2组比较,差异均有统计学意义(P<0.05)。结论银杏叶提取物延缓肺动脉高压的产生过程,其与抑制ET-1的释放、维持eNOS的合成有关;相比低中剂量,高剂量GEB可增强延缓肺动脉高压形成的作用,有一定剂量依赖性。

Objective To study the effect of different doses of Ginkgo biloba extract(GBE)in monocrotaline-induced pulmonary arterial hypertension,and to measure the expression of endothelin-1(ET-1)and nitric oxide synthase(eNOS)in lung tissue.Methods According to the random number table method,50 male SD rats were divide into five groups:normal control group(group C),pulmonary arterial hypertension model group(group M),GBE low-dose treatment group(group G1,40 mg/kg),GBE medium-dose treatment group(group G2,60 mg/kg)and the GBE high-dose treatment group(group G3,80 mg/kg),10 rats in each group.The right atrial pressure(RAP),right ventricular systolic pressure(RVSP),mean pulmonary artery pressure(mPAP)and right ventricular hypertrophy index(RVHI)in rats were measured.The histological structure of small pulmonary arteries was observed by HE staining,and the percentage of mesothelial thickness to the outer diameter of the vessel(MA%)and ratio of the mesothelial area to the total area of the vessel(MV%)for 50-150μm diameter pulmonary arteries were calculated.The expression of ET-1 and eNOS in lung tissue of rats was determined by immunohistochemistry.Results Compared with the group M,the RAP,mPAH,RVSP,RVHI,MA%and MV%of the rats in the three treatment groups decreased,and the differences were statistically significant(P<0.05).Among the three treatment groups,RAP,mPAH and MV%in group G3 were statistically significant compared with group G1(P<0.05).In eNOS,the expression of eNOS in five groups:group C>group G3>group G1>group G2>group M,the expression levels of eNOS in the three treatment groups were higher than those in the group M,and the differences were statistically significant(P<0.05).The expression of eNOS in the G3 group was compared with the group G1 and group G2,and the differences were statistically significant(P<0.05).In ET-1,the expression of ET-1 in five groups:group M>group G1>group G2>group G3>group C,the expression levels of ET-1 in the three treatment groups were lower than those in the group M,and the differences were statistically significant(P<0.05).The expression of ET-1 in the G3 group was compared with the group G1 and group G2,and the differences were statistically significant(P<0.05).Conclusion GBE can delay the formation of pulmonary arterial hypertension,which is related to inhibiting the release of ET-1 and maintaining the synthesis of eNOS.Compared with low and medium doses,high doses of GEB could enhance the delaying effect formation of pulmonary arterial hypertension in a dose-dependent manner.