盐酸戊乙奎醚对野百合碱致大鼠肺动脉高压的抑制作用

Inhibiting effect of hydrochloric penehyclidine on rat pulmonary hypertension induced by monocrotaline

目的：探讨盐酸戊乙奎醚是否能够减缓野百合碱导致的大鼠肺动脉高压及是否能够预防或缓解肺血管重构。方法3~4周龄健康雄性 SD 大鼠30只,体重90~100 g,随机均分为正常对照组（C 组）、野百合碱肺高压组（M 组）、盐酸戊乙奎醚组（P 组）,每组10只。M 组和 P 组腹腔注射野百合碱60 mg/kg 建造大鼠肺动脉高压模型,C 组腹腔注射等容量生理盐水。P 组大鼠于建模前15 min 时腹腔注射盐酸戊乙奎醚2 mg/kg,建模第2天腹腔注射盐酸戊乙奎醚1 mg/kg,C 组和 M 组在相应时点腹腔注射等容量生理盐水,连续使用3周。在建模后第21天,三组大鼠检测血流动力学（肺动脉压、右心室压）；处死大鼠前采集静脉血以备血液生化检测：ELISA 法检测一氧化氮（NO）含量、内皮素-1（ET-1）含量。处死大鼠后留取左肺组织行病理切片以观察肺组织病理形态学变化,取右肺组织于-80℃冻存以备后续检测。结果 M 组和 P 组右心室 SBP、平均肺动脉压、肺动脉 SBP 和肺动脉 DBP 明显高于 C 组（P 〈0.05）；P 组右心室 SBP、平均肺动脉压、肺动脉 SBP 和肺动脉 DBP 明显低于 M 组（P 〈0.05）。M 组肺小动脉明显增厚,肺小动脉管腔狭窄甚至闭塞,肺组织炎性细胞浸润非常明显。P 组肺小动脉壁增厚减轻,肺组织炎性细胞浸润减轻。M 组大鼠血清中 NO 含量明显低于,ET-1的含量明显高于 C 组（P 〈0.05）；P 组大鼠血清中 NO 含量明显高于 M组和 C 组（P 〈0.05）,ET-1含量明显高于 C 组,但明显低于 M 组（P 〈0.05）。结论使用野百合碱成功建造了大鼠肺动脉高压模型,NO 含量降低、ET-1含量增加可能与野百合碱致大鼠肺动脉高压的形成有关；盐酸戊乙奎醚减缓野百合碱致大鼠肺动脉高压模型的肺动脉压力的升高、改善肺小动脉壁增厚可能与增加 NO 含量、降低 ET-1含量有关。

Objective To explore whether hydrochloride penehyclidine can inhibit rat pulmonary hypertension induced by monocrotaline and prevent or relieve the remodeling of pulmonary vascular.Methods Thirty healthy male SD rats （aged 3-4 weeks,weighing 90-100 g）were randomly divided into normal control group （group C）,monocrotaline pulmonary hypertension group （group M）and hydrochloride penehyclidine treatment group （group P,n = 10 each）.Rat pulmonary hyper-tension model was established by abdominally injecting 60 mg/kg monocrotaline all at once;The con-trol group was abdominally injected equal volume of normal saline all at once;the treatment group P 2 mg/kg hydrochloric penehyclidine 1 5 minutes before model building 1 mg/kg hydrochloric penehyclid-ine two days after model building;while the other two groups received equal volume of normal saline as placebo at the same time of medicine injecting,which lasted consecutively for 3 weeks.21 days af-ter model building,the haemodynamics （pulmonary artery pressure and right ventricular pressure） test was performed for all groups;Venous blood was sampled for blood biochemical tests （using ELISA method to test the content of NO and ET-1 ）before executing the rats.The left lung tissue was sliced to observe the pathological morphological changes of lung tissues.The right lung tissue was cryopreserved for other tests.Results Compared with the normal control group,the pulmonary artery pressure and right ventricular pressure of monocrotaline pulmonary hypertension group notably enhanced （P 〈0.05）;The pulmonary arterioles strongly thickened;The lumen of pulmonary arteri-oles became narrow and even blocked;The inflammatory cells of lung tissues apparently infiltrated. When compared with the monocrotaline pulmonary hypertension group, the pulmonary artery pressure and right ventricular pressure of the hydrochloride penehyclidine treatment group greatly lowered （P 〈0.05）;Both the thickening degree of pulmonary arterioles walls and the infiltrating de-gree of inflammation cells of lung tissues lessened.When compared with the normal control group, the NO content of other groups significantly lowered and the ET-1 content apparently increased;When compared with the monocrotaline pulmonary hypertension group,the NO content of hydrochlo-ride penehyclidine treatment group was higher and the ET-1 content was lower.The differences were statistically significant （P 〈0.05）.Conclusion The rat pulmonary hypertension model has been suc-cessfully built with the help of monocrotaline.The reducing of NO content and increasing of ET-1 was relevant to the formation of rat pulmonary hypertension induced by monocrotaline;The fact that hy-drochloric penehyclidine lowered the pulmonary artery pressure of rat pulmonary hypertension model and improved the thickening degree of pulmonary arterioles walls might involve the increasing of NO cotent and reducing of ET-1 content.