摘要
目的观察七龙天对低氧性肺动脉高压(HPH)大鼠白细胞介素-1β(IL-1β)、肿瘤坏死因-α(TNF-α)的影响。方法将雄性SD大鼠随机分为6组:正常组、模型组、波生坦组、七龙天低剂量组、七龙天中剂量组、七龙天高剂量组。正常组大鼠置于正常环境中饲养,除正常组外所有实验大鼠均采用常压低氧法制模,从制模第1天始给药,连续3周。在直视下行右心导管术测定肺血流动力学参数,以RT-PCR法检测肺组织中IL-1β、TNF-α的mRNA表达及免疫组织化学技术检测IL-1β、TNF-α在肺小动脉内膜中的蛋白表达。结果七龙天及波生坦组均可明显降低大鼠肺动脉高压,且以七龙天高剂量组效果为佳,疗效呈药物剂量依赖表现。与正常组比较,各组的IL-1β、TNF-α表达水平(包括mRNA及蛋白)均有所增加,尤以模型组、波生坦组呈非常显著性差异(P<0.01);与模型组比较,波生坦组无显著性差异(P>0.05),七龙天各组可明显下调IL-1β、TNF-α表达水平(P<0.01或P<0.05),以七龙天高、中剂量组更为显著(P<0.01或P<0.05)。结论不同剂量七龙天均可降低肺动脉高压,且高剂量七龙天疗效优于波生坦。其降压机制与降低IL-1β及TNF-α表达量有关,但仍可能受其他血管张力因子及血管新生因子影响。
Objective To study the effects of Qilongtian on interleukin-1β（ IL-1β） and tumor necrosis factor-α（ TNF-α） in hypoxic pulmonary hypertension（ HPH） rats. Methods All male rats were randomly divided into six groups： normal group,model group,bosentan group,Qilongtian high-,mid- and low- group. Except the rats in normal group,those in other five groups were under atmospheric hypoxia to establish HPH model. From the first day of modeling,all medication groups were i. g corresponding drugs for consecutive three weeks. Pulmonary hemodynamic parameters were detected by right heart catheterization under direct vision,mRNA expression of IL-1β and TNF-α in lung tissue were measured using ELISA,protein expression of IL-1β and TNFα in lung tissue were measured using immunohistochemistrical methods. Results Qilongtian and bosentan significantly reduced the level of mean pulmonary arterial pressure（ MPAP）,IL-1β and TNF-α expression in HPH rats,and the effect of Qilongtian high dosage was stronger with the dose-dependence. Compared with normal group,expression of IL-1β and TNF-αmRNA and protein increased,and those in model group and bosentan group did significantly（ P 〈0. 01）.Compared with the model group,there was no significant difference in bosentan group（ P 〉0. 05）,the expression level of IL-1β and TNF-α were significantly downregulated in all Qilongtian groups（ P 〈0. 01 or P 〈0. 05）. Compared with the bosentan group and all the Qilongtian groups,there were significant differences,and the Qilongtian high-,mid- dose group had more impact（ P 〈0. 01 or P 〈0. 05）. Conclusion High,middle and low dosage of Qilongtian reduced pulmonary hypertension,with high dosage prior to bosentan. The mechanism of lower blood pressure may be via downregulating the expression of IL-1β and TNF-α,but it would be influenced by other vascular tension factors and angiogenic factors.
出处
《北京中医药大学学报》
CAS
CSCD
北大核心
2016年第11期915-919,共5页
Journal of Beijing University of Traditional Chinese Medicine
基金
国家自然科学基金资助项目(No.81160467)
