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研究间尼索地平对野百合碱诱导的肺动脉高压的防治作用及其作用机制。大鼠单剂量皮下注射野百合碱(60 mg.kg-1)制备肺动脉高压模型。导管法测定肺血流动力学指标;光镜观察肺小动脉结构的改变;同时测定血清中MDA及SOD的含量(活性);免疫印迹法测定PCNA、ERK1和p-ERK的表达水平;免疫组化法观察5-HT和PCNA的表达。结果表明,与正常对照组相比,模型组大鼠的平均肺动脉压及右心指数明显增加;肺小动脉肌化程度加重;丙二醛含量显著升高,超氧化物歧化酶活性明显降低;PCNA和5-HT阳性细胞数目明显增加;PCNA蛋白表达及p-ERK/ERK1比率也显著增加,不同剂量间尼索地平在一定程度上逆转了上述变化。间尼索地平对野百合碱诱导的肺动脉高压表现出一定的保护作用。这一作用可能与其降低5-HT的表达,抑制ERK/MAPK信号通路有关。
To study the prevention and treatment of nisoldipine on monocrotaline-induced pulmonary hypertension and its mechanism. Rats were injected subcutaneously with monocrotaline (60 mg.kg-1) to prepare pulmonary hypertension model. The indexes of pulmonary hemodynamics were determined by catheterization method. The changes of structure of pulmonary arterioles were observed with light microscope. The content of MDA and SOD in serum were measured simultaneously. The expressions of PCNA, ERK1 and p-ERK were detected by immunoblotting. Method to observe the expression of 5-HT and PCNA. The results showed that compared with the normal control group, the mean pulmonary arterial pressure and right heart index in model group were significantly increased; the pulmonary arterial muscle was more muscular; the content of malondialdehyde was significantly increased and the activity of superoxide dismutase was significantly decreased; The number of PCNA and 5-HT positive cells increased obviously. The expression of PCNA and the ratio of p-ERK / ERK1 also increased significantly. Nisoldipine reversed the above changes to a certain extent. Nisoldipine showed some protective effect on monocrotaline-induced pulmonary hypertension. This effect may be related to its reduction of 5-HT expression, inhibition of ERK / MAPK signaling pathway.