新加金水六君煎对野百合碱诱导肺动脉高压模型大鼠ET-1和NO水平及肺组织血管中TGF-β1的影响

Effects of Xinjia Jinshui Liujun Decoction on ET-1 and NO levels and pulmonary vascular TGF-β1 in monocrotaline-induced pulmonary hypertension rat model

目的:探讨新加金水六君煎对野百合碱诱导肺动脉高压模型大鼠血浆内皮素-1(ET-1)和一氧化氮(NO)水平及肺组织血管中转化生长因子-β1(TGF-β1)的影响。方法:50只雄性SPF级Wistar大鼠采用腹腔注射野百合碱造大鼠肺心病肺动脉高压模型,14d后随机分为模型组(0.9%氯化钠溶液2m L/d灌胃)、硝苯地平组(0.03g/kg),附子半夏组(2.25g/kg)、金水六君煎组(8.875g/kg)、新加金水六君煎组(8.875g/kg),另设10只未造模大鼠为空白组灌服0.9%氯化钠溶液,连续灌胃15d。最后一次给药24h后,麻醉大鼠,取血,分别测定血浆中ET-1及NO水平,并观察肺组织血管中TGF-β1的表达。结果:模型组大鼠血浆ET-1水平显著升高、血清NO水平显著降低、肺组织中TGF-β1表达广泛呈强阳性表达(P<0.01),说明模型大鼠内皮功能下降;各给药组可使血浆ET-1水平降低、血清NO水平提高、肺组织中TGF-β1阳性表达都有不同程度的抑制(P<0.01)。结论:新加金水六君煎可改善血浆ET-1和NO水平,抑制肺组织中TGF-β1阳性表达,作用机制可能与其对肺血管内皮细胞的保护作用有关。

Objective： To investigate the effects of Xinjia Jinshui Liujun Decoction（XJL） on the plasma endothelin-1（ET-1） and NO levels and pulmonary vascular transforming growth factor-β1（TGF-β1） in monocrotaline（MCT）-induced pulmonary hypertension rat model. Methods： Fifty male SPF grade Wistar rats were collected and the pulmonary hypertension with pulmonary heart disease rat model was intraperitoneally injected with MCT. The model rats were randomly divided into 5 groups after 14 d, and respectively administrated by gavage with nifedipine（0.03g/kg）, Fuzi-Banxia（2.25g/kg）, Jinshui Liujun Decoction（8.875g/kg）, XJL（8.875g/kg） and the same volume of normal saline, while the control group was set up with 10 healthy normal rats administrated with the same volume of normal saline, once a day for continuous 15 d. 24 h after the last administration, the rats were anesthetized and the blood was collected to detect the levels of ET-1 and NO and to observe the expression of TGF-β1 in lung tissue of vascular. Results： The level of ET-1 was significantly increased, the level of NO was significantly decreased, and TGF-β1 in lung tissue expression was wide with strong positive in the model group,（P〈0.01）, which suggested the model rats could decrease endothelial function. Each treatment group reduced the level of ET-1, improved the level of NO and inhibited the TGF-β1 expression in lung tissue to varying degrees（P〈0.01）. Conclusion： XJL could improve the level of ET-1 and NO and inhibit the TGF-β1 expression, the mechanism might be related to the protective effect on pulmonary vascular endothelial cells.