DCDDP对肺动脉高压大鼠SOD活性和MDA含量的影响

Effects of DCDDP, a dihydropyridine calcium antagonist, on SOD activity and MDA concentration in rat with pulmonary hypertension

目的：探讨2，6-二甲基-4－（2-氯苯基）-1，4-二氢-3，5-吡啶二羧酸二甲酯（DCDDP）对野百合碱（MCT）引起肺动脉高压（PH）时大鼠血浆和肺组织匀浆中超氧化物歧化酶（SOD）活性和丙二醛（MDA）含量的影响．方法：在给MCT（60mg·kg-1，sc）前30min和后每日腹腔注射不同刘量（5，50，500μg·kg－1）DCDDP-次，用化学比色法测定SOD活性和MDA含量变化，用彩色图像分析仪观察肺小血管组织病理学的变化．结果；在注射MCT后4WK，大鼠静脉血浆和肺匀浆中SOD活性（106±45，317±59NU·L-1）明显低于对照组（155±28，505±47NU.L－1P分别为＜0．05和＜0．o1）、DCDDP能有效地阻止MCT引起的SOD活性下降，尤以中、低剂量组效果为佳（P分别为＜0.05和＜0．01）．MCT组血浆和肺匀浆中MDA含量（15±5，59±14μmol·L－1）明显高于对照组（5.3±2.9，32±19μmol·L－1,P〈0.01），三种不同剂量的DCDDP都能够显著对抗肺匀浆中MCT引起的MDA含量升高（P<0.01）．结论：DCDDP对MCT引起大鼠PH时血浆和肺匀浆中SOD活性的下降和肺匀浆中MDA含量的升高有明显的抑制作用，并能减轻MCT引起的淋巴细胞浸润现象，抑制肺小动脉管壁的变化，且以中、小剂量效果明显．这可能与其升高肺组织中NO含量有关，提示DCDDP对防治肺动脉?

Aim: To investigate the effect of dimethyl 4-(2-chlorophenyl )-1, 4-dihydro-2, 6-dimethyl-3, 5-pyridinedi-carboxylate (DCDDP), a dihydropyridine calcium antagonist, on superoxide dismutase (SOD) activity and malondialdehyde (MDA ) concentration in plasma and pulmonaryhomogenate in rat with pulmonary hypertension (PH ),mold of PH was Induced by a singal subcutaneous injectionof monocrotaline (MCT, 60 mg·kg-1). Methods: Threedoses (5, 50, 500 μp·kg-1 ) of DCDDP were injected by ip30 min before and once daily after MCT injection. Thechanges in SOD activity and MDA concentration were me-asured by colorimetric analysis, histopathologic changes inlung and pulmonary small arteries were observed withcolour image analysis system. Results: Four weeks after injection of MCT, the SOD activity in plasma (106 ± 45 NU·L-1 ) and pulmonary homogenate (317 ± 59 NU· L-1 ) weresignificant lower than that of control (155 ± 28, 505 ± 47 re-spectively P < 0. 05 or P < 0. 01 ). The MDA content inplasma (15±μmol· L-1 ) and pulmonary homogenate （59± 14 μmol·L-1 ) in MCT group were significant higherthan that of control (5. 3± 2. 9, 32 ± 19 μmol·L-1, P〈0' 05 or P< 0. 01 ). DCDDP can effectively inhibit the de-crease in SOD activity, especially in middle dose (147 ±17,421 ± 54 NU·L-1) and low dose (173±29,406±73NU·L-1 P< 0. 05,or P< 0.01 )and prevent the MDA content increased by MCT in pulmonary homogenate (P < 0.01 ).Conclusion: DCDDP can significantly inhibit the SOD activi-ty lowered and prevent the MDA content elevated by MCTin plasma and pulmonary homogenate. These may be relat-ed to its mechanism of NO elevated in Pulmonary ho-mogenate and treatment PH.