药学学报
藥學學報
약학학보
ACTA PHARMACEUTICA SINICA
2008年
10期
1011-1018
,共8页
陈雪彦%张伟%苗庆峰%张永健
陳雪彥%張偉%苗慶峰%張永健
진설언%장위%묘경봉%장영건
肺动脉高压%5-羟色胺%野百合碱%间尼索地平
肺動脈高壓%5-羥色胺%野百閤堿%間尼索地平
폐동맥고압%5-간색알%야백합감%간니색지평
pulmonary hypertension%5-hydroxytryptamine%monocrotaline%m-niseldipine
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 nag·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.
研究間尼索地平對野百閤堿誘導的肺動脈高壓的防治作用及其作用機製.大鼠單劑量皮下註射野百閤堿(60 nag·kg-1)製備肺動脈高壓模型.導管法測定肺血流動力學指標;光鏡觀察肺小動脈結構的改變;同時測定血清中MDA及SOD的含量(活性);免疫印跡法測定PCNA、ERK1和p-ERK的錶達水平;免疫組化法觀察5-HT和PCNA的錶達.結果錶明,與正常對照組相比,模型組大鼠的平均肺動脈壓及右心指數明顯增加;肺小動脈肌化程度加重;丙二醛含量顯著升高,超氧化物歧化酶活性明顯降低;PCNA和5-HT暘性細胞數目明顯增加;PCNA蛋白錶達及p-ERK/ERK1比率也顯著增加,不同劑量間尼索地平在一定程度上逆轉瞭上述變化.間尼索地平對野百閤堿誘導的肺動脈高壓錶現齣一定的保護作用.這一作用可能與其降低5-HT的錶達,抑製ERK/MAPK信號通路有關.
연구간니색지평대야백합감유도적폐동맥고압적방치작용급기작용궤제.대서단제량피하주사야백합감(60 nag·kg-1)제비폐동맥고압모형.도관법측정폐혈류동역학지표;광경관찰폐소동맥결구적개변;동시측정혈청중MDA급SOD적함량(활성);면역인적법측정PCNA、ERK1화p-ERK적표체수평;면역조화법관찰5-HT화PCNA적표체.결과표명,여정상대조조상비,모형조대서적평균폐동맥압급우심지수명현증가;폐소동맥기화정도가중;병이철함량현저승고,초양화물기화매활성명현강저;PCNA화5-HT양성세포수목명현증가;PCNA단백표체급p-ERK/ERK1비솔야현저증가,불동제량간니색지평재일정정도상역전료상술변화.간니색지평대야백합감유도적폐동맥고압표현출일정적보호작용.저일작용가능여기강저5-HT적표체,억제ERK/MAPK신호통로유관.
Effect of new calcium antagonist m-nisoldipine (m-Nis) on MCT-induced PH in rats and its mechanisms were investigated. Rats were injected with a single doxe(60mg·kg-1)of MCT subcutaneously to induce PH. Pulmonary haemedynamic measurement and lung tissue morphological investigations were undertaken. The MDA production and SOD activity in the serum were tested. PCNA,ERK1 and p-ERK expressions were analyzed by Western blotting. The expressions of 5-HT and PCNA were observed with immunohistochemistry. Results suggested that the PAP, right ventricular index and the degree of muscularization of small pulmonary artery were elevated markedly in MCT group, which was attenuated by m-Nis treatment. A significant reduction in MDA production and an increase in the SOD activity in the serum were also observed in all three m-Nis groups. The number of PCNA and 5-HT positive smooth muscle cells increased significantly in MCT group, and m-Nis treatment attenuated the expression obviously. Western blotting results suggested that the protein expression of PCNA and the ratio of p-ERK/ERK1 increased markedly in MCT group and decreased by m-Nis. In conclusion, m-Nis protected against MCT-induced PH by decreasing PAP, right ventricular index, PAMSCs proliferation and pulmonary artery remodelling, which may be related to the reduction of 5-HT and the suppression of the ERK/MAPK signal pathway.