外源性apelin对大鼠慢性低氧性肺动脉高压的防治作用

Protective and therapeutic fffect of apelin on chronic hypoxic pulmonary hypertension in rats

目的:探讨外源性给予小分子活性肽apelin对大鼠慢性低氧性肺动脉高压和肺血管重构的作用及其机制。方法:采用常压低氧法建立SD大鼠低氧性肺动脉高压模型。实验分4组(n=10)对照组(NC)、低氧组(HH)、低氧+apelin低剂量组(5nmol/(kg.d)(LA)和低氧+apelin高剂量组(10nmol/(kg.d)(HA),HA组和LA组通过皮下埋植微量渗透泵持续给药。低氧4周后,测定平均肺动脉压(mPAP)、右心室与左心室加室间隔的重量比[RV/(LV+S)]、肺细小动脉管壁面积/管总面积(WA/TA)、管腔面积/管总面积(CA/TA)、中膜厚度(PAMT)以及肺组织超氧化物歧化酶(SOD)活性与丙二醛(MDA)含量。结果:①mPAP和RV/(LV+S):HH组较NC组高,HA组较HH组低;LA组mPAP较HH低,而RV/(LV+S)两组间无显著性差异。②WA/TA和PAMT:HH组较NC组高,HA组、LA组均较HH低。③CA/TA:HH组较NC组低,HA组、LA组均较HH高。④肺组织SOD含量:HH组较NC低,HA组、LA组均较HH高。⑤MDA含量:HH组较NC高,HA组、LA组均较HH低。结论:Apelin对低氧性肺动脉高压和肺血管重构的形成具有防治作用,这种作用可能与直接舒张肺血管作用及改善氧化应激有关。

Objective：To study the role of apelin in the prevention of pulmonary hypertension induced by hypoxia in rats.Methods：The animal model of hypoxic pulmonary hypertension was established by exposing the rats to isobaric hypoxic chamber for 4 weeks （8 h/d,6 d/w）.Fourty male Sprague-Dawley rats were randomly divided into control group（NC）,hypoxic group（HH）,hypoxic with low-dose apelin（5 nmol/（kg·d） group（LA） and high-dose apelin（10 nmol/（kg.d） （HA）.[pGlu]apelin-13 was administered into the rats of apelin groups by mini-osmotic pump subcutaneously.The mean pulmonary arterial pressure（mPAP） and the mean carotid arterial pressure（mCAP） were measured by either right or left cardiac catheterization,and the weight ratio of right ventricule/left ventricule plus septum （RV/（LV＋S）） were calculated.The Masson＇s trichrome stained lung specimens were examined by light microscope to examine the vessel wall area/total area（WA/TA）,vessel cavity area/total area（CA/TA） and media thickness of pulmonary arterioles（PAMT）.Meanwhile,the lung homogenates were assayed for the activity of superoxide dismutase（SOD） and the content of malondialdehyde（MDA）.Results：①mPAP and RV/（LV＋S） of HH group were significantly higher than those of NC group.mPAP of LA and HA groups were lower than those of HH group.The RV/（LV＋S） of HA group was significantly lower than that of HH group,but there was no significant difference between HH group and LA group.②Masson＇s trichrome staining revealed that WA/TA and PAMT of HH group were higher than those of NC group.Administration of apelin significantly eliminated WA/TA and PAMT in LA and HA groups.③CA/TA of HH group was lower than that of NC group.Administration of apelin significantly elevated CA/TA in LA and HA groups.④The activity of SOD and content of MDA in HH group was,respectively,lower and higher than those in NC group.Apelin treatment increased the activity of SOD in LA and HA groups while decreased the content of MDA.Conclusions：Apelin could play an important role in treatment of hypoxic pulmonary hypertension of rats and the mechanisms of protection were associated with vasodilation of pulmonary artery and inhibition of oxidative stress.