葛根素改善慢性肺心病大鼠肺血管重建机制探讨

Mechanism of Puerarin on Pulmonary Vascular Remodeling in Rats with Chronic Pulmonary Hypertension Induced by Hypoxia and Hypercapnia

关键词:  葛根素；低氧  慢性；高碳酸血；高血压  肺性；基质金属蛋白酶

Key words:  puerarin  hypoxia  chronic  hypercapnia  hypertension  pulmonary  matrix metalloproteinases

摘要:

目的探讨葛根素对慢性低氧高二氧化碳大鼠肺血管重建的作用。方法图像分析、氯胺T法、免疫组化、组织原位杂交技术等方法观察葛根素对慢性低氧高二氧化碳大鼠肺组织羟脯氨酸含量、肺小血管显微结构、肺动脉管壁MMP-2、MMP-9及其基因的影响。结果①光镜下葛根素组内弹力板扭曲、中膜平滑肌细胞增生及管腔狭窄程度均明显轻于低O2高CO2组。②血浆NO含量低O2高CO2组低于正常对照组(P<0.01),葛根素组高于低O2高CO2组(P<0.01)。③氯胺T法发现肺组织羟脯氨酸含量低O2高CO2组高于正常对照组(P<0.01),葛根素组低于低O2高CO2组(P<0.01)。④肺组织匀浆MMP-2、MMP-9含量低O2高CO2组高于正常对照组（P<0.01）。葛根素组肺组织匀浆MMP-2、MMP-9含量皆低于低O2高CO2组（P<0.01）。⑤免疫组化、原位杂交法发现肺细小动脉MMP-2、MMP-9和MMP-2mRNA、MMP-9mRNA平均吸光度值低O2高CO2组均高于正常对照组（P<0.01），葛根素组均低于低O2高CO2组(P<0.01)。结论葛根素改善慢性低氧高二氧化碳大鼠肺血管重建，与其调节MMPs表达、抑制肺动脉管壁胶原的沉积有关。

Abstract:

OBJECTIVE To study the effects of puerarin on pulmonary vascular remodeling in rats with pulmonary hypertension induced by chronic hypoxia and hypercapnia .METHODS Thirty Sp rague-Dawley rats were randomly divided into normal control group (NC) , hypoxic hypercapnia group (HH) and hypoxic hypercapnia + puerarin group (HP). Mean pulmonary arterial pressure (mPAP) and mean carotid arterial pressure (mCAP) were measured. MMP-2,MMP-9 and their mRNA were observed in pulmonary arterioles by the technique of immunohistochemistry and in situ hybridization. RESULTS (1)mPAP was significantly higher in rats of HH group than that of NC group and it was much lower in rats of HP group than that of HH group(P<0.01).Differences of mCAP were not significant in three groups.(2)Light microscopy showed media thickness of pulmonary arterioles was much higher in HH group than that of NC group,and vessel cavity turned more straiter in HH group than that of NC group.Howerer, the damage of pulmpnary arterioles in HP group was much slighter than that of HH group. (3) The levels of lung homogenates Hyr,MMP-2 and MMP-9 were much higher in rats of HH group than those of NC group(P<0.01),and lower in HP group than HH group (P<0.01).Plasma NO content of group HH was lower than that of group NC（P<0.01），it was highter in group HP than that of group HH（P<0.01）.(4)Expression of MMP-2,MMP-9 and their mRNA in pulmonary arterioles were significantly higher in rats of HH groups than those of NC group (P<0.01)，and they were lower in rats of HP group than those of HH group (P<0.01).CONCLUSION Puerarin can improve pulmonary vessel remodeling by regulate MMPs system in hypoxic hypercapnic rats.